Here are the studies that match your search criteria. If you are interested in participating, please reach out to the contact listed for the study. If no contact is listed, contact us and we'll help you find the right person.
Comparing Two Methods to Follow Patients With Pancreatic Cysts
The purpose of this study is to compare the two approaches for monitoring pancreatic cysts.
The study doctors want to compare more frequent monitoring vs less frequent monitoring in
order to learn which monitoring method leads to better outcome for patients with pancreatic
cysts.
• Patient must be ≥ 50 years and ≤ 75 years of age.
• Patient must not have acute pancreatitis or a history of chronic pancreatitis.
• Patient must have received a CT, MRI, or EUS within 6 months prior to randomization
that revealed one or more ≥ 1 cm pancreatic cyst (s).
• Patients of childbearing potential must not be known to be pregnant.
• Patient must not have a prior diagnosis of pancreatic malignancy of any type.
• Patient must not have a history of pancreatic resection.
• Patients with only pancreatic lesions without malignant risk (pancreatic pseudocyst or
classic serous cystic lesion) are not eligible.
• Patient must not have a family history of pancreatic adenocarcinoma in one or more
first degree relatives(biological parents, full siblings or children).
• Patient must not have pancreatic cyst morphology that would prompt immediate surgical
consideration (enhancing mural nodule, solid component in cyst, pancreatic duct ≥10mm,
cyst causing obstructive jaundice).
• Patient must not have a comorbid illness that precludes pancreatic cyst resection.
• Patient must not be participating in any form of pancreatic cyst surveillance.
Testing the Use of the Usual Chemotherapy Before and After Surgery for Removable Pancreatic Cancer
This phase III trial compares perioperative chemotherapy (given before and after surgery)
versus adjuvant chemotherapy (given after surgery) for the treatment of pancreatic cancer
that can be removed by surgery (removable/resectable). Chemotherapy drugs, such as
fluorouracil, irinotecan, leucovorin, and oxaliplatin, work in different ways to stop the
growth of tumor cells, either by killing the cells, by stopping them from dividing, or by
stopping them from spreading. Giving chemotherapy before and after surgery (perioperatively)
may work better in treating patients with pancreatic cancer compared to giving chemotherapy
after surgery (adjuvantly).
PRE-REGISTRATION:
• Pathology: Histologic or cytologic proof of pancreatic adenocarcinoma or adenosquamous
carcinoma
• TNM Stage: Tx-4, N0-1, M0 (M0 disease does not include spread to distant lymph nodes
and organs)
• Resectable Primary Tumor: Local radiographic reading must be consistent with
resectable disease defined as the following on 1) arterial and venous phase
contrast-enhanced abdominal/pelvic CT scan or abdominal/pelvic magnetic resonance
imaging (MRI) scan and 2) chest CT:
• No involvement or abutment of the celiac artery, common hepatic artery, superior
mesenteric artery, or replaced right hepatic artery (if applicable)
• Less than 180 degree interface between tumor and vessel wall of the portal vein
or superior mesenteric vein, and patent portal vein/splenic vein confluence
• No evidence of metastatic disease
• Measurable disease or non-measurable disease o Non-measurable disease is defined as
cytologic or histologic confirmation of adenocarcinoma of adenosquamous carcinoma by
fine needle aspiration or core-biopsy of the pancreas without measurable disease by
radiographic imaging
REGISTRATION:
• Confirmation of resectable disease by real-time central imaging review by the Alliance
Imaging Core Lab at Imaging and Radiation Oncology Core (IROC) Ohio
• Determined to be appropriate candidate for curative-intent pancreatectomy by surgeon
intending to perform the resection
• No prior radiation therapy, chemotherapy, targeted therapy, investigational therapy,
or surgery for pancreatic cancer
• Not pregnant and not nursing, because this study involves an agent that has known
genotoxic, mutagenic, and teratogenic effects.
• Therefore, for women of childbearing potential only, a negative pregnancy test done =<
14 days prior to registration is required
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Total Neuropathy Score < 2
• Absolute neutrophil count (ANC) >= 1,500/uL
• Platelet count >= 100,000/uL
• Total bilirubin =< 1.5 x upper limit of normal (ULN) (If obstructive jaundice is
present, then biliary drainage must be initiated and total bilirubin =< 3.0)
• Creatinine =< 1.5 x ULN OR calculated (Calc.) creatinine clearance >= 30 mL/min
(Calculated using the Cockcroft-Gault equation)
• No known Gilbert's Syndrome or known homozygosity for UGAT1A1*28 polymorphism
• No comorbid conditions that would prohibit curative-intent pancreatectomy
• Chronic concomitant treatment with strong inhibitors of CYP3A4 is not allowed on this
study. Patients on strong CYP3A4 inhibitors must discontinue the drug prior to
registration
• Chronic concomitant treatment with strong inducers of CYP3A4 is not allowed on this
study. Patients on strong CYP3A4 inducers must discontinue the drug prior to
registration
Phase 2b Study of GC4711 in Combination With SBRT for Nonmetastatic Pancreatic Cancer
GTI-4711-201 is designed as a Phase 2b, multicenter, randomized, double-blind,
placebo-controlled study to determine the effect to OS by adding GC4711 to SBRT following
chemotherapy in patients with unresectable or borderline resectable nonmetastatic
1. Histological or biopsy proven adenocarcinoma of the pancreas. Cytology is acceptable
if histology cannot be obtained.
2. Newly diagnosed non-metastatic PC judged by tumor board to be feasible for SBRT
3. Completed at least 6 weeks of chemotherapy consisting of FOLFIRINOX, mFOLFIRINOX, or a
gemcitabine-based doublet regimen prior to start of SBRT
4. Remain non-metastatic as confirmed by a CT scan at screening.
5. Female or male subjects ≥ 18 years of age
6. ECOG performance status of 0-2
7. Adequate end-organ function
Exclusion Criteria:
1. Subjects with documented metastatic disease
2. First-line chemotherapy other than FOLFIRINOX, mFOLFIRINOX, and/or a gemcitabine-based
doublet regimen
3. Prior abdominal RT with substantial overlap in radiation fields
4. Subjects not recovered/controlled from treatment-related toxicities
5. Uncontrolled malignancy other than PC
6. Uncontrolled gastric or duodenal ulcer disease within 30 days of dosing
7. Visible invasion of bulky tumor into the lumen of the bowel or stomach on endoscopy
Drug: Drug GC4711, Drug: Placebo
Unresectable Pancreatic Cancer, Pancreas, SBRT, Borderline Resectable Pancreatic Cancer
UT Southwestern; Parkland Health & Hospital System
Comparing Two Treatment Combinations, Gemcitabine and Nab-Paclitaxel With 5-Fluorouracil, Leucovorin, and Liposomal Irinotecan for Older Patients With Pancreatic Cancer That Has Spread
This phase II trial compares two treatment combinations: gemcitabine hydrochloride and
nab-paclitaxel, or fluorouracil, leucovorin calcium, and liposomal irinotecan in older
patients with pancreatic cancer that has spread to other places in the body (metastatic).
Drugs used in chemotherapy, such as gemcitabine hydrochloride, nab-paclitaxel, fluorouracil,
leucovorin calcium, and liposomal irinotecan, work in different ways to stop the growth of
tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them
from spreading. This study may help doctors find out which treatment combination is better at
prolonging life in older patients with metastatic pancreatic cancer.
• Newly diagnosed untreated metastatic adenocarcinoma of the pancreas. However, previous
surgery, adjuvant chemotherapy and/or radiation therapy will be allowed, provided
radiation therapy is completed at least 2 weeks prior to registration and adjuvant
therapy was administered more than 6 months prior to registration. Patients with the
following histology are excluded: acinar cell; adenosquamous carcinoma
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Patient is an English speaker with the ability to understand and complete the informed
consent and questionnaires
• Leukocytes >= 3,000/mcL (obtained within 4 weeks of registration)
• Absolute neutrophil count >= 1,500/mcL (obtained within 4 weeks of registration)
• Platelets >= 100,000/mcL (obtained within 4 weeks of registration)
• Total bilirubin =< institutional upper limit of normal (ULN) (obtained within 4 weeks
of registration)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
=< 2.5 x institutional ULN (obtained within 4 weeks of registration)
• Creatinine =< institutional ULN unless data exists supporting safe use at lower kidney
function values, no lower than 30 mL/min/1.73 m^2 (obtained within 4 weeks of
registration)
• Glomerular filtration rate (GFR) >= 40 mL/min/1.73 m^2 unless data exists supporting
safe use at lower kidney function values, no lower than 30 mL/min/1.73 m^2 (obtained
within 4 weeks of registration)
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral
therapy with undetectable viral load within 6 months of registration are eligible for
this protocol. HIV positive (+) patients who are on ritonavir or/and cobicistat-based
regimen must be switched to alternative anti-retroviral therapy (ART)
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral
load must be undetectable on suppressive therapy, if indicated
• Patients with a history of hepatitis C virus (HCV) infection must have been treated
and cured. For patients with HCV infection who are currently on treatment, they are
eligible if they have an undetectable HCV viral load
• Male patients must agree not to father children while on study
• Patients with known history or current symptoms of cardiac disease, or history of
treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac
function using the New York Heart Association functional classification. To be
eligible for this protocol, patients should be class 2B or better
• Patients must have measurable disease and scans must be done within 4 weeks of
registration
• Patients classified to have mild-moderate abnormalities in any of the domains
evaluated in the screening geriatric assessment and are classified as "vulnerable" are
eligible. Patients classified without any abnormalities ("fit") or with severe
cognitive/functional impairment or high co-morbidity score ("frail") on the screening
geriatric assessment are ineligible
• Patients must agree not to take any medications or substances that are strong
inhibitors or inducers of CYP3A4. Those who are randomized to liposomal irinotecan
treatment arm should avoid drugs that are UGT1A1 inhibitors
A Study of ASP2138 in Adults With Stomach Cancer or Pancreatic Cancer
ASP2138 is a potential new treatment for people with stomach cancer, gastroesophageal
junction cancer, or pancreatic cancer. Before ASP2138 is available as a treatment, the
researchers need to understand how it is processed by and acts upon the body. They do this to
find a suitable dose and to check for potential medical problems from the treatment.
People who are 18 years or older can take part. This is an open-label study. This means that
people in this study will know that they will receive ASP2138.
The study will have 2 phases. Phase 1 is called dose escalation. Different small groups of
people will take lower to higher doses of ASP2138. Medical problems will be recorded at each
dose. This is done to find suitable doses of ASP2138 to use later in the study. Doctors will
also check how each type of cancer is responding to ASP2138.
Phase 1b is called dose expansion. Other different small groups will take part, and will take
suitable doses of ASP2138 found from phase 1. This phase will check how each type of cancer
responds to ASP2138. The response to ASP2138 is measured using x-rays, scans and blood tests.
Doctors will continue to check all medical problems throughout the study.
ASP2138 will be given through a vein in the arm. This is called an infusion. People will
continue to receive treatment until: their disease gets worse; they have medical problems
they can't tolerate; they ask to stop treatment; the doctors decide that continuing treatment
is no longer in that person's best interest; the study is ended by the sponsor. Study doctors
will check for any medical problems from ASP2138. Other checks will include physical exams,
checking the nervous system, laboratory tests and vital signs. Nervous system checks include
checking reflexes, balance, movement and muscle strength. Vital signs include body
temperature, blood pressure and pulse. Electrocardiograms (ECG) will be done to check the
heart rhythm during the study. People will receive ASP2138 in a hospital. They will give
blood samples and study doctors will check for medical problems. People will also visit the
clinic on certain days during their treatment, with extra visits during the first 3 cycles of
treatment.
People will visit the clinic after treatment has finished. The study doctors will check for
more medical problems. Other checks will include physical exams, laboratory tests and vital
signs. People will also have an ECG.
After this, people will visit the clinic for a check-up several times. The number of visits
and checks done at each visit will depend on the health of each person and whether they
completed their treatment or not.
• Participant is considered an adult according to local regulation at the time of
signing the informed consent form (ICF).
• Female participant is not pregnant, confirmed by serum pregnancy test and medical
evaluation by interview and at least 1 of the following conditions apply:
• Not a woman of childbearing potential (WOCBP)
• WOCBP who agrees to follow the contraceptive guidance from the time of informed
consent through at least 6 months after final study intervention administration.
• Female participant must agree not to breastfeed starting at screening and throughout
the study period and for 6 months after the final study intervention administration.
• Female participant must not donate ova starting at screening and throughout the study
period and for 6 months after the final study intervention administration.
• Male participant with female partner(s) of childbearing potential (including
breastfeeding partner) must agree to use contraception throughout the treatment period
and for 6 months after the final study intervention administration.
• Male participant must not donate sperm during the treatment period and for 6 months
after the final study intervention administration.
• Male participant with pregnant or breastfeeding partner(s) must agree to remain
abstinent or use a condom for the duration of the pregnancy or time partner is
breastfeeding throughout the study period and for 6 months after the final study
intervention administration.
• Participant's tumor sample is positive for claudin (CLDN)18.2 expression by central
immunohistochemistry (IHC) testing.
• Participant has radiographically-confirmed, locally advanced, unresectable or
metastatic disease within 28 days prior to the first dose of study intervention.
• Participant has measurable disease according to Response Evaluation Criteria in Solid
Tumors (RECIST) 1.1 within 28 days prior to the first dose of study intervention. For
participant with only 1 measurable lesion and prior radiotherapy, the lesion must be
outside the field of prior radiotherapy or must have documented progression following
radiation therapy.
• Participant has QT interval by Fredericia (QTcF) =< 470 msec.
• Participant agrees not to participate in another interventional study while receiving
study treatment in the present study.
• Participant has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
1.
• Participant has predicted life expectancy >= 12 weeks.
• Participant must meet all of criteria based on laboratory tests within 7 days prior to
the first dose of study drug. In case of multiple laboratory data within this period,
the most recent data should be used. If a participant has received a recent blood
transfusion, the laboratory tests must be obtained >= 2 weeks after any blood
transfusion.
Disease Specific Criteria: Gastric/GEJ Cancer
• Participant has histologically confirmed gastric or gastroesophageal junction (GEJ)
adenocarcinoma.
• Participant with gastric or GEJ adenocarcinoma who has progressed, is intolerant, has
refused, or for whom there is no standard approved therapies that impart significant
clinical benefit (no limit to the number of prior treatment regimens).
Disease Specific Criteria: Pancreatic Cancer
• Participant has histologically or cytologically confirmed pancreatic adenocarcinoma.
• Participant with pancreatic adenocarcinoma who has progressed, is intolerant, has
refused, or for whom there is no standard approved therapies that impart significant
clinical (no limit to the number of prior treatment regimens).
Exclusion Criteria:
• Participant has received other investigational agents, or antineoplastic therapy
including immunotherapy or devices concurrently or within 21 days or 5 times the
half-life, whichever is shorter, prior to first dose of study intervention
administration.
• Participant has any condition which makes the participant unsuitable for study
participation.
• Participant has known immediate or delayed hypersensitivity or contraindication to any
component of study treatment.
• Participant has had prior severe allergic reaction or intolerance to known ingredients
of ASP2138 or other antibodies, including humanized or chimeric antibodies.
• Participant weighs < 40 kg.
• Participant has received systemic immunosuppressive therapy, including systemic
corticosteroids 14 days prior to first dose of study intervention. Participant using a
physiologic replacement dose of hydrocortisone or its equivalent (defined as up to 30
mg per day of hydrocortisone or up to 10 mg per day of prednisone), receiving a single
daily dose of systemic corticosteroids or receiving systemic corticosteroids as
pre-medication for radiologic imaging contrast use are allowed.
• Participant has a complete gastric outlet syndrome or a partial gastric outlet
syndrome with persistent/recurrent vomiting.
• Participant has significant gastric bleeding and/or untreated gastric ulcers that
exclude the participant from participation.
• Participant has symptomatic CNS metastases or participant has evidence of unstable CNS
metastases even if asymptomatic (e.g., progression on scans). Participants with
previously treated CNS metastases are eligible, if they are clinically stable and have
no evidence of CNS progression by imaging for at least 4 weeks prior to start of study
treatment and are not requiring immunosuppressive doses of systemic steroids (> 30 mg
per day of hydrocortisone or > 10 mg per day of prednisone or equivalent) for longer
than 2 weeks.
• Participant is known to have HIV infection. However, participants with cluster of
differentiation (CD4) + T cell counts >= 350 cells/µL and no history of acquired
immunodeficiency syndrome (AIDS)-defining opportunistic infections within the past 6
months are eligible. NOTE: Screening for human immunodeficiency virus (HIV) infection
should be conducted per local requirements.
• Participant is known to have active hepatitis B (positive hepatitis B surface antigen
[HBsAg]) or hepatitis C infection. Testing is required for known history of these
infections or as mandated by local requirements. NOTE: Screening for these infections
should be conducted per local requirements.
• For participant who is negative for HBsAg, but hepatitis B core antibody (HBc Ab)
positive, a hepatitis B virus (HBV) deoxyribonucleic acid (DNA) test will be
performed and if positive the participant will be excluded.
• Participant with positive hepatitis C virus (HCV) serology, but negative HCV
ribonucleic acid (RNA) test results are eligible.
• Participant treated for HCV with undetectable viral load results are eligible
• Participant has had within 6 months prior to first dose of study intervention any of
the following: unstable angina, myocardial infarction, ventricular arrhythmia
requiring intervention or hospitalization for heart failure.
• Participant has active infection requiring systemic therapy that has not completely
resolved within 7 days prior to the start of study intervention.
• Participant has active autoimmune disease that has required systemic immunosuppressive
treatment within the past 1 month prior to the start of study intervention.
• Participant has a clinically significant disease or co-morbidity that may adversely
affect the safe delivery of treatment within this study or make the participant
unsuitable for study participation.
• Participant has psychiatric illness or social situations that would preclude study
compliance.
• Participant has had a major surgical procedure 28 days before start of study
intervention and has not fully recovered.
• Participant has received radiotherapy for locally advanced unresectable or metastatic
gastric or GEJ or metastatic pancreatic adenocarcinoma 14 days prior to start of study
intervention and has NOT recovered from any related toxicity.
• Participant has another malignancy for which treatment is required.
• Participant who has received an CLDN18.2-targeted investigational agent (e.g.,
zolbetuximab or chimeric antigen receptor CLDN18.2-specific T cells) prior to first
dose of study intervention administration is not eligible for dose escalation cohorts.
However, a participant who has received an CLDN18.2-targeted investigational agent
greater than 28 days or 5 half-lives (whichever is longer) prior to first dose study
intervention administration is eligible for dose expansion cohorts only, with the
exception of participants who have experienced Grade >= 3 gastrointestinal (GI)
toxicity after receiving an CLDN18.2-targeted investigational agent.
• Participant has a history or complication of interstitial lung disease.
Drug: ASP2138
Pancreatic Adenocarcinoma, Gastric Adenocarcinoma, Other Digestive Organ, Pancreas, Stomach, Small Intestine, Gastroesophageal Junction (GEJ) Adenocarcinoma
Efficacy and Safety of Olaparib (MK-7339) in Participants With Previously Treated, Homologous Recombination Repair Mutation (HRRm) or Homologous Recombination Deficiency (HRD) Positive Advanced Cancer (MK-7339-002 / LYNK-002)
This study will evaluate the efficacy and safety of olaparib (MK-7339) monotherapy in
participants with multiple types of advanced cancer (unresectable and/or metastatic) that: 1)
have progressed or been intolerant to standard of care therapy; and 2) are positive for
homologous recombination repair mutation (HRRm) or homologous recombination deficiency (HRD).
• Has a histologically- or cytologically-confirmed advanced (metastatic and/or
unresectable) solid tumor (except breast or ovarian cancers whose tumor has a germline
or somatic BRCA mutation) that is not eligible for curative treatment and for which
standard of care therapy has failed. Participants must have progressed on or be
intolerant to standard of care therapies that are known to provide clinical benefit.
There is no limit on the number of prior treatment regimens.
• Has either centrally-confirmed known or suspected deleterious mutations in at least 1
of the genes involved in HRR or centrally-confirmed HRD.
• For participants receiving prior platinum (cisplatin, carboplatin, or oxaliplatin
either as monotherapy or in combination) for advanced (metastatic and/or unresectable)
solid tumor, have no evidence of disease progression during the platinum chemotherapy.
• Has measurable disease per RECIST 1.1 or PCWG-modified RECIST 1.1 as assessed by the
local site Investigator/radiology and confirmed by BICR.
• Is able to provide a newly obtained core or excisional biopsy of a tumor lesion or
either an archival formalin-fixed paraffin embedded (FFPE) tumor tissue block or
slides.
• Has a life expectancy of at least 3 months.
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of either 0 or 1,
as assessed within 3 days of treatment initiation.
• Male participants must agree to use contraception during the treatment period and for
at least 90 days (3 months) after the last dose of study treatment and refrain from
donating sperm during this period.
• Female participants must not be pregnant or breastfeeding. Additionally, female
participants must either not be a woman of childbearing potential (WOCBP) or, if a
WOCBP, agree to use contraception during the treatment period and for at least 30 days
(1 month) after the last dose of study treatment.
• Has adequate organ function.
Exclusion Criteria:
• Has a known additional malignancy that is progressing or has required active treatment
in the last 5 years. Note: Participants with basal cell carcinoma of the skin,
squamous cell carcinoma of the skin, ductal carcinoma in situ, or cervical carcinoma
in situ that has undergone potentially curative therapy are not excluded.
• Has myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or with features
suggestive of MDS/AML.
• Has known central nervous system (CNS) metastases and/or carcinomatous meningitis.
Note: Participants with previously treated brain metastases may participate if
radiologically stable, clinically stable, and without requirement for steroid
treatment for at least 14 days prior to the first dose of study treatment.
• Has received colony-stimulating factors (e.g., granulocyte colony-stimulating factor
[G-CSF], granulocyte-macrophage colony-stimulating factor [GM-CSF] or recombinant
erythropoietin) within 28 days prior to the first dose of study treatment.
• Has a known history of human immunodeficiency virus (HIV) infection.
• Has known active hepatitis infection (i.e., Hepatitis B or C).
• Is unable to swallow orally administered medication or has a gastrointestinal disorder
affecting absorption (e.g., gastrectomy, partial bowel obstruction, malabsorption).
• Has received prior therapy with olaparib or with any other polyadenosine 5'
diphosphoribose (poly[ADP ribose]) polymerization (PARP) inhibitor.
• Has a known hypersensitivity to the components or excipients in olaparib.
• Has received previous allogenic bone-marrow transplant or double umbilical cord
transplantation (dUCBT).
• Has received a whole blood transfusion in the last 120 days prior to entry to the
study. Packed red blood cells and platelet transfusions are acceptable if not
performed within 28 days of the first dose of study treatment.
A Study of Repotrectinib (TPX-0005) in Patients With Advanced Solid Tumors Harboring ALK, ROS1, or NTRK1-3 Rearrangements (TRIDENT-1)
Phase 1 dose escalation will determine the first cycle dose-limiting toxicities (DLTs), the
maximum tolerated dose (MTD), the biologically effective dose and recommended Phase 2 dose
(RP2D) of repotrectinib given to adult subjects with advanced solid malignancies harboring an
ALK, ROS1, NTRK1, NTRK2, or NTRK3 gene rearrangement.
Midazolam DDI substudy will examine effect of of repotrectinib on CYP3A induction.
Phase 2 will determine the confirmed Overall Response Rate (ORR) as assessed by Blinded
Independent Central Review (BICR) of repotrectinib in each subject population expansion
cohort of advanced solid tumors that harbor a ROS1, NTRK1, NTRK2, or NTRK3 gene
rearrangement. The secondary objective will include the duration of response (DOR), time to
response (TTR), progression-free survival (PFS), overall survival (OS) and clinical benefit
rate (CBR) of repotrectinib in each expansion cohort of advanced solid tumors that harbor a
ROS1, NTRK1, NTRK2, or NTRK3 gene rearrangement.
1. Histologically or cytologically confirmed diagnosis of locally advanced, or metastatic
solid tumor (including primary CNS tumors) (Stage IV, American Joint Committee on
Cancer v.7) that harbors an ALK, ROS1, NTRK1, NTRK2, or NTRK3 gene rearrangement by
protocol specified tests.
2. ECOG PS 0-1.
3. Age ≥18 (or age ≥ 20 of age as required by local regulation).
4. Capability to swallow capsules intact (without chewing, crushing, or opening).
5. At least 1 measurable target lesion according to RECIST version 1.1. CNS-only
measurable disease as defined by RECIST version 1.1 is allowed.
6. Prior cytotoxic chemotherapy is allowed.
7. Prior immunotherapy is allowed.
8. Resolution of all acute toxic effects (excluding alopecia) of any prior anti-cancer
therapy to National Cancer Institute Common Terminology Criteria for Adverse Events
(NCI CTCAE) Version 4.03 Grade less than or equal to 1.
9. Patients with asymptomatic CNS metastases (treated or untreated) and/or asymptomatic
leptomeningeal carcinomatosis are eligible to enroll if they satisfy the protocol
specified criteria.
10. Baseline laboratory values fulfilling the following requirements:Absolute neutrophils
count (ANC) ≥1500/mm3 (1.5 × 109/L); Platelets (PLTs) ≥100,000/mm3 (100 × 109/L);
Hemoglobin ≥ 9.0 g/dL transfusions are allowed; Serum creatinine or creatinine
clearance Within normal limits or > 40 mL/min; Total serum bilirubin < 1.5 × ULN;
Liver transaminases (ASTs/ALTs) < 2.5 × ULN; < 5 × ULN if liver metastases are present
Alkaline phosphatase (ALP); < 2.5 × ULN; < 5 × ULN if liver and/or bone metastasis are
present; Serum calcium, magnesium, and potassium Normal or CTCAE grade ≤ 1 with or
without supplementation
11. Life expectancy ≥ 3 months.
PHASE 2 Key Inclusion Criteria
1. Histologically or cytologically confirmed diagnosis of locally advanced, or metastatic
solid tumor (including primary CNS tumors) that harbors a ROS1, or NTRK1-3 gene
fusion.
2. Subject must have a documented ROS1 or NTRK1-3 gene fusion determined by tissue-based
local testing using either:
1. a next-generation sequencing (NGS) or quantitative polymerase chain reaction
(qPCR) test will be accepted to determine molecular eligibility.
• Adequate tumor tissue needs to be sent to the Sponsor designated central
diagnostic laboratory for retrospective confirmation by a central diagnostic
laboratory test selected by the Sponsor.
OR
2. a fluorescence in situ hybridization (FISH) test AND prospective confirmation of
fusion status by a central diagnostic laboratory test selected by the Sponsor
PRIOR to enrollment will be accepted to determine molecular eligibility.
• Adequate tumor tissue must be sent to the Sponsor designated central
diagnostic laboratory for prospective confirmation by a central diagnostic
laboratory test selected by the Sponsor PRIOR to enrollment.
3. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1.
4. Age ≥12 (or age ≥ 20 as required by local regulation).
5. Willing and able to provide written institutional review board (IRB)/institutional
ethics committee-approved Informed Consent or an Assent signed by a parent or legal
guardian for subjects age 12 to 17.
6. At least 1 measurable target lesion according to RECIST (v1.1) prospectively confirmed
by Blinded Independent Central Radiology Review (BICR), selected by Sponsor, PRIOR to
enrollment. Subjects with CNS-only measurable disease ≥10 mm as defined by RECIST
(v1.1) are eligible.
7. Subjects with advanced solid tumors harboring ROS1, NTRK1, NTRK2, or NTRK3
rearrangement will be assigned into 6 distinct expansion (EXP) cohorts provided all
inclusion and exclusion criteria are met.
i. EXP-1: ROS1 TKI-naïve ROS1+ NSCLC ii. EXP-2: 1 Prior ROS1 TKI and 1 Platinum based
chemo ROS1+ NSCLC iii. EXP-3: 2 Prior ROS1 TKIs ROS1+ NSCLC (No Chemo or IO) iv.
EXP-4: 1 Prior ROS1 TKI ROS1+ NSCLC (No Chemo or IO) v. EXP-5: TRK TKI-naïve NTRK+
solid tumors vi. EXP-6: TRK TKI-pretreated NTRK+ solid tumors
8. Subjects with asymptomatic CNS metastases (treated or untreated) and/or asymptomatic
leptomeningeal carcinomatosis are eligible to enroll if they satisfy the protocol
specified criteria.
9. Baseline laboratory values fulfilling the following requirements:Absolute neutrophils
count (ANC) ≥1500/mm3 (1.5 × 109/L); Platelets (PLTs) ≥100,000/mm3 (100 × 109/L);
Hemoglobin ≥ 9.0 g/dL transfusions are allowed; Serum creatinine or creatinine
clearance > 40 mL/min; Total serum bilirubin < 1.5 × ULN; Liver transaminases
(ASTs/ALTs) < 2.5 × ULN; < 5 × ULN if liver metastases are present Alkaline
phosphatase (ALP); < 2.5 × ULN; < 5 × ULN if liver and/or bone metastasis are present;
Serum calcium, magnesium, and potassium Normal or CTCAE grade ≤ 1 with or without
supplementation
10. Life expectancy ≥ 3 months.
Key Exclusion Criteria PHASE 1 and PHASE 2
1. Concurrent participation in another therapeutic clinical trial.
2. Symptomatic brain metastases or leptomeningeal involvement.
3. History of previous cancer, except for squamous cell or basal-cell carcinoma of the
skin, or any in situ carcinoma that has been completely resected, requiring therapy
within the previous 2 years.
4. Major surgery within 4 weeks of start of repotrectinib treatment. Radiation therapy
(except palliative to relieve bone pain) within 2 weeks of study entry. Palliative
radiation (≤10 fractions) must have been completed at least 48 hours prior to study
entry
5. Clinically significant cardiovascular disease (either active or within 6 months prior
to enrollment): myocardial infarction, unstable angina, coronary/peripheral artery
bypass graft, symptomatic congestive heart failure (New York Heart Association
Classification Class ≥ II), cerebrovascular accident or transient ischemic attack,
symptomatic bradycardia, requirement for anti-arrhythmic medication. Ongoing cardiac
dysrhythmias of NCI CTCAE grade ≥2
6. Any of the following cardiac criteria:
Mean resting corrected QT interval (ECG interval measured from the onset of the QRS
complex to the end of the T wave) for heart rate (QTcF) > 470 msec obtained from 3
ECGs, using the screening clinic ECG machine-derived QTc value Any clinically
important abnormalities in rhythm, conduction or morphology of resting ECG (e.g.,
complete left bundle branch block, third degree heart block, second degree heart
block, PR interval > 250 msec) Any factors that increase the risk of QTc prolongation
or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT
syndrome, family history of long QT syndrome, or any concomitant medication known to
prolong the QT interval.
7. Known active infections (bacterial, fungal, viral including HIV positivity).
8. Gastrointestinal disease (e.g., Crohn's disease, ulcerative colitis, or short gut
syndrome) or other malabsorption syndromes that would impact drug absorption.
9. Peripheral neuropathy of CTCAE ≥grade 2.
10. History of extensive, disseminated, bilateral, or presence of CTCAE grade 3 or 4
interstitial fibrosis or interstitial lung disease including a history of pneumonitis,
hypersensitivity pneumonitis, interstitial pneumonia, interstitial lung disease,
obliterative bronchiolitis, and pulmonary fibrosis. Subjects with history of prior
radiation pneumonitis are not excluded.
Safety and Efficacy Study of IMSA101 in Refractory Malignancies
Open-label, dose escalation (Phase I) and dose expansion (Phase IIA) study of patients
receiving intra-tumoral IMSA101 alone or in combination with an immune checkpoint inhibitor
(ICI) (Phase I and II)
1. Signed informed consent and mental capability to understand the informed consent
2. Male or female patients > 18 years of age
3. Histologically or cytologically documented locally advanced or metastatic solid tumor
malignancies refractory to or otherwise ineligible for treatment with standard-of-care
agents/regimens, including but not limited to:
• Malignant melanoma
• Hormone receptor negative breast cancer
• Gastro-esophageal cancer
• Non-small cell lung cancer
• Head and neck cancer
• Hepatoma
• Renal cell carcinoma
4. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1
5. Evaluable or measurable disease as follows:
• A minimum of 3 RECIST-evaluable lesions: one that is suitable for injection and
biopsied; one non-injected that will be biopsied for abscopal effect; and one
measurable lesion that will be followed for response only.
• Injectable tumors shall be accessed by intralesional (cutaneous) or percutaneous
injection only, including those lesions that are visible, palpable, or detectable
by standard radiographic or ultrasound methods. Neither surgical procedures nor
endoscopically-guided injections including those to endobronchial, endoluminal,
or endosinusial spaces shall be allowed. While no anatomic locations are required
or disallowed, lesions selected for intratumoral injection must, in the opinion
of the investigator:
• Not be immediately adjacent to blood vasculature or other physiologic landmarks
in such a way that will accrue undue safety risk to the patient
• Have longest diameter ≥ 10 mm and ≤ 50 mm
• Be fully efficacy evaluable per RECIST v1.1 criteria
6. Life expectancy > 3 months (Phase I) and > 6 months (Phase IIA)
7. ECG without evidence of clinically meaningful conduction abnormalities or active
ischemia as determined by the investigator
8. Acceptable organ and marrow function as defined below:
• Absolute neutrophil count > 1,500 cells/μL
• Platelets > 50,000 cells/μL
• Total bilirubin ≤ 1.5 times the upper limit of normal (ULN)
• Aspartate aminotransferase (AST)/alanine transaminase (ALT) ≤ 2.5 times ULN. If
liver metastases are present, AST/ALT < 5 times ULN
• Serum creatinine < 1.5 mg/dL and a measured creatinine clearance ≥ 50 mL/min
using the Cockcroft-Gault formula
• Prothrombin time (PT)/partial thromboplastin time (PTT) ≤ 1.5 times ULN
9. Women of child-bearing potential (defined as a female who has experienced menarche and
who has not undergone successful surgical sterilization (hysterectomy, bilateral
salpingectomy, or bilateral oophorectomy) or is not postmenopausal (defined as
amenorrhea for at least 12 consecutive months with an appropriate clinical profile at
the appropriate age, e.g., greater than 45 years) must have a negative serum pregnancy
test prior to first dose of study drug
10. Male and female patients with reproductive potential must agree to use two forms of
highly effective contraception throughout the study
11. Phase I combination only: Demonstrated RECIST stable disease through ≥ 4 consecutive
cycles of an approved PD-1 or PD-L1 targeted ICI with no Grade ≥ 3 CTCAE events
considered by the investigator to be drug-related.
Exclusion Criteria:
1. Anti-cancer therapy within 4 weeks or < 5 half-lives of the first dose of study drug.
2. Failure to recover to Grade 1 or less from clinically significant AEs due to prior
anti-cancer therapy.
3. Known untreated brain metastases or treated brain metastases that have not been stable
(scan showing no worsening of central nervous system (CNS) lesion[s] and no
requirement of corticosteroids) ≥ 4 weeks prior to study enrollment
4. Baseline prolongation of QT/QTc interval (QTc interval > 470)
5. Uncontrolled intercurrent illness (including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations) that in opinion of the
investigator would limit compliance with study requirements
6. Women who are pregnant or breastfeeding
7. Phase I combination only: Prior tumor progression through PD-1 or PD-L1 targeted ICI
therapy.
• Histologically or cytologically documented locally advanced or metastatic solid tumor
malignancy.
• Progressed or was intolerant to all available therapies known to confer clinical
benefit appropriate for their tumor type, and for which the patient was eligible and
willing to receive, or refused SOC treatments that are perceived to have marginal
clinical benefit.
• Adequate bone marrow, kidney and liver function.
• Performance status of 0 or 1.
• Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade 1
except for AEs not constituting a safety risk by Investigator judgement.
Exclusion Criteria:
• Prior treatment targeting ILT2 and/or ILT4 or targeting HLA-G.
Drug: NGM707, Drug: NGM707 plus pembrolizumab, Drug: NGM707, Drug: NGM707, Drug: NGM707, Drug: NGM707 plus pembrolizumab, Drug: NGM707 plus pembrolizumab
Esophageal Cancer, Breast Cancer, Melanoma, Gastric Cancer, Colorectal Cancer, Ovarian Cancer, Glioblastoma, Cervical Cancer, Renal Cell Carcinoma, Non Small Cell Lung Cancer, Mesothelioma, Cholangiocarcinoma, Pancreatic Ductal Adenocarcinoma, Brain and Nervous System, Breast - Female, Breast - Male, Kidney, Liver, Lung/Thoracic, Melanoma, skin, Other Digestive Organ, Other Skin, Ovary, Pancreas, Squamous Cell Carcinoma of Head and Neck, Endocervical Cancer
Niraparib in the Treatment of Patients With Advanced PALB2 Mutated Tumors (PAVO)
The purpose of this study is to further evaluate the efficacy and safety of niraparib in
patients with locally advanced or metastatic solid tumors and a pathogenic or likely
pathogenic tumor PALB2 (tPALB2) mutation.
• Participants must be at least 18 years of age or older.
• Participants must have a histologically or cytologically confirmed diagnosis of
locally advanced or metastatic solid tumor(s).
• Participants must have tested positive for a pathogenic or likely pathogenic tPALB2
gene mutation using a CLIA-certified laboratory as described in the Next-Generation
Sequencing (NGS) Laboratory Manual.
• Participants who have stable and asymptomatic Central Nervous System (CNS) disease
must be receiving a stable (for at least 7 days) or decreasing corticosteroid dose at
the time of study entry.
• Participants must submit fresh or archived (collected within 24 months of enrollment)
Formalin-Fixed Paraffin-Embedded (FFPE) tumor sample to the central laboratory for
post-enrollment confirmation of tPALB2 status.
• Participants must have received all standard therapies appropriate for their tumor
type and stage of disease or, in the opinion of the Investigator, the patient would be
unlikely to tolerate or derive clinically meaningful benefit from appropriate standard
of care therapy, or the participant has no satisfactory alternative treatments.
Exclusion Criteria:
• Participants have other active concomitant malignancy that warrants systemic,
biologic, or hormonal therapy.
• Participants who have ovarian or prostate cancer.
• Participants who have variants of undetermined significance (VUS), but not pathogenic
variants of PALB2, at the time of screening.
• Participants who relapsed while receiving platinum based therapy in the
adjuvant/curative setting.
• Participants progressing within 14-18 weeks while receiving platinum based therapy in
the metastatic setting.
• Participants who have received Poly (ADP-ribose) polymerase (PARP) inhibitor(s) in
prior lines of treatment.
• Participants with leptomeningeal disease, carcinomatous meningitis, symptomatic brain
metastases, or radiologic signs of CNS hemorrhage.
• Participants with germline or somatic BRCA1 or BRCA2 mutations.
• Participant has systolic blood pressure (BP) over 140 mmHg or diastolic BP over 90
mmHg, despite optimal medical therapy.
• Participants have previously or are currently participating in a treatment study of an
investigational agent within 3 weeks of the first dose of therapy preceding the study.
• Participants have received prior systemic cytotoxic chemotherapy, biological therapy,
or hormonal therapy for cancer, or received radiation therapy within 3 weeks of the
first dose therapy preceding the study.
Drug: Niraparib
Endometrial Cancer, Esophageal Cancer, Melanoma, Pancreatic Cancer, Metastatic Cancer, Head and Neck Cancer, Solid Tumor, Breast - Female, Colon, Corpus Uteri, Esophagus, Lung/Thoracic, Melanoma, skin, Other Urinary, Pancreas, Breast Tumor, Colon Tumor, Malignant, Lung Tumor, Urologic Cancer, Locally Advanced Solid Tumor
PALB2, Solid Tumor, Metastatic Solid Tumor, Locally Advanced Solid Tumor, Advanced Solid Tumor, Local Solid Tumor, PALB2 Mutation, Niraparib, tPALB2, tPALB2 Mutation, Pathogenic tumor, Lung Tumor, Breast Tumor, Colon Tumor, Zejula, Pancreatic Cancer, Urologic Cancer, Melanoma, Metastatic Cancer, Head and Neck Cancer, Endometrial Cancer, Esophageal Cancer
Tabelecleucel for Solid Organ or Allogeneic Hematopoietic Cell Transplant Participants With Epstein-Barr Virus-Associated Post-Transplant Lymphoproliferative Disease (EBV+ PTLD) After Failure of Rituximab or Rituximab and Chemotherapy (ALLELE)
The purpose of this study is to determine the clinical benefit and characterize the safety
profile of tabelecleucel for the treatment of Epstein-Barr virus-associated post-transplant
lymphoproliferative disease (EBV+ PTLD) in the setting of (1) solid organ transplant (SOT)
after failure of rituximab and rituximab plus chemotherapy or (2) allogeneic hematopoietic
cell transplant (HCT) after failure of rituximab.
1. Prior SOT of kidney, liver, heart, lung, pancreas, small bowel, or any combination of
these (SOT cohort); or prior allogeneic HCT (HCT cohort)
2. A diagnosis of locally-assessed, biopsy-proven EBV+ PTLD
3. Availability of appropriate partially HLA-matched and restricted tabelecleucel has
been confirmed by the sponsor
4. Measurable, 18F-deoxyglucose (FDG)-avid (Deauville score ≥ 3) systemic disease using
Lugano Classification response criteria by positron emission tomography
(PET)-diagnostic computed tomography (CT), except when contraindicated or mandated by
local practice, then magnetic resonance imaging (MRI) may be used.For subjects with
treated central nervous system (CNS) disease, a head CT and/or brain/spinal MRI as
clinically appropriate will be required to follow CNS disease response per Lugano
Classification response criteria.
5. Treatment failure of rituximab or interchangeable commercially available biosimilar
monotherapy (SOT subgroup A or HCT cohort) or rituximab plus any concurrent or
sequentially administered chemotherapy regimen (SOT subgroup B) for treatment of PTLD.
6. Eastern Cooperative Oncology Group performance status ≤ 3 for subjects aged ≥ 16
years; Lansky score ≥ 20 for subjects < 16 years
7. For HCT cohort only: If allogeneic HCT was performed as treatment for an acute
lymphoid or myeloid malignancy, the underlying primary disease for which the subject
underwent transplant must be in morphologic remission
8. Adequate organ function
1. Absolute neutrophil count ≥ 1000/μL, (SOT cohort) or ≥ 500/μL (HCT cohort), with
or without cytokine support
2. Platelet count ≥ 50,000/μL, with or without transfusion or cytokine support. For
HCT cohort, platelet count < 50,000/μL but ≥ 20,000/μL, with or without
transfusion support, is permissible if the subject has not had grade ≥ 2 bleeding
in the prior 4 weeks (where grading of the bleeding is determined per the
National Cancer Institute's Common Terminology Criteria for Adverse Events
[CTCAE], version 5.0)
3. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total
bilirubin each < 5 × the upper limit of normal; however, ALT, AST, and total
bilirubin each ≤ 10 × upper limit of normal is acceptable if the elevation is
considered by the investigator to be due to EBV and/or PTLD involvement of the
liver as long as there is no known evidence of significant liver dysfunction
9. Subject or subject's representative is willing and able to provide written informed
consent
Exclusion Criteria:
1. Burkitt lymphoma, classical Hodgkin lymphoma, or any T cell lymphoma
2. Daily steroids of > 0.5 mg/kg prednisone or glucocorticoid equivalent, ongoing
methotrexate, or extracorporeal photopheresis
3. Untreated CNS PTLD or CNS PTLD for which the subject is actively receiving
CNS-directed chemotherapy (systemic or intrathecal) or radiotherapy at enrollment.
NOTE:Subjects with previously treated CNS PTLD may enroll if CNS-directed therapy is
complete.
4. Suspected or confirmed grade ≥ 2 graft-versus-host disease (GvHD) per the Center for
International Blood and Marrow Transplant Research consensus grading system at
enrollment
5. Ongoing or recent use of a checkpoint inhibitor agent (eg, ipilimumab, pembrolizumab,
nivolumab) within 3 drug half-lives from the most recent dose to enrollment
6. For HCT cohort: active adenovirus viremia
7. Need for vasopressor or ventilatory support
8. Antithymocyte globulin or similar anti-T cell antibody therapy ≤ 4 weeks prior to
enrollment
9. Treatment with Epstein-Barr virus cytotoxic T lymphocytes or chimeric antigen receptor
T cells directed against B cells within 8 weeks of enrollment (SOT or HCT cohorts), or
unselected donor lymphocyte infusion within 8 weeks of enrollment (HCT cohort only)
10. Female who is breastfeeding or pregnant or female of childbearing potential or male
with a female partner of childbearing potential unwilling to use a highly effective
method of contraception
11. Inability to comply with study-related procedures
Evaluation of [18F]FLT PET/CT as an Early Predictor of Outcome in Pediatric Solid Tumors
The experimental [18F]FLT-PET/CT will be completed before initiation of chemotherapy at
either diagnosis or initiation of salvage chemotherapy at relapse and prior to the third
cycle (or month) of chemotherapy. Laboratory analysis and correlative radiology, as directed
per clinical care based on the primary diagnosis, are required within 30 days of the baseline
[18F]FLT PET/CT. Follow-up will comprise 24 months of standard practice treatment and follow
up.
• Patients with histologically confirmed solid tumor malignancies with residual tumors
present that require standard of care chemotherapy for a minimum number of cycles. All
anatomical sites and all tumor histologies are eligible including central nervous
system tumors. Both newly diagnosed and/or newly relapsed patients are eligible.
• Patients ages 8 •25 years
• In the opinion of the investigator, patients must be thought to be able to lie still
for imaging without sedation for 20 •30 minutes.
• Patients must have a performance status of > 50% (Lansky or Karnofsky).
• Patients of childbearing potential must have a negative urine or serum pregnancy test
as per institution's standard of care within 7 days prior to [18F]FLT PET/CT imaging.
• Ability to understand and the willingness to sign a written informed consent/assent.
Exclusion Criteria:
• Patients with known allergic or hypersensitivity reactions to previously administered
radiopharmaceuticals of similar chemical or biologic composition to [18F]FLT
• Newly diagnosed subjects who had prior chemotherapy or radiotherapy before enrollment
in the study. Relapsed patients are eligible prior to starting their relapsed
chemotherapy regimen if they meet the other eligibility criteria.
• Subjects for whom chemotherapy is not a standard of care primary therapy option.
• Patients who are pregnant or breast-feeding.
• Patients with no residual tumor (i.e. complete resection at diagnosis or relapse).
Drug: [18F]FLT-PET/CT
Sarcoma, Solid Tumor, Brain and Nervous System, Eye and Orbit, Anus, Breast - Female, Breast - Male, Carcinoid Tumor, Cervix, Colon, Corpus Uteri, Ear, Esophagus, Gall Bladder, Head and Neck, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung/Thoracic, Melanoma, skin, Nose, Ovary, Pancreas, Prostate, Rectum, Stomach, Throat, Thyroid, Urinary Bladder, Uterine (Endometrial), Vulva, Small Intestine, Soft Tissue
Abatacept in Immune Checkpoint Inhibitor Myocarditis (ATRIUM)
The primary aim is to test whether abatacept, as compared to placebo, is associated with a
reduction in major adverse cardiac events (MACE) among participants hospitalized with
myocarditis secondary to an immune checkpoint inhibitor (ICI). The primary outcome, MACE, is
a composite of first occurrence of cardiovascular death, non-fatal sudden cardiac arrest,
cardiogenic shock, significant ventricular arrythmias, significant bradyarrythmias, or
incident heart failure.
1. Must have provided informed consent in a manner approved by the Investigator's
Institutional Review Board (IRB) prior to any study-related procedure being performed.
If a participant is unable to provide informed consent due to his/her medical
condition, the participant's legally authorized representative may consent on behalf
of the study participant, as permitted by local law and institutional Standard
Operating Procedures;
2. Aged greater than or equal to 18 years at the time of informed consent;
3. Recent use of an FDA-approved immune checkpoint inhibitor (ICI, defined as
administered an immune checkpoint inhibitor ≤ 6 months of myocarditis diagnosis),
alone or in combination with other cancer therapies (i.e. chemotherapy, radiation
therapy or targeted therapy). The FDA-approved ICI could be given as part of a
clinical trial but not in combination with a new investigational agent which may cause
myocarditis;
4. A diagnosis of myocarditis.
5. Hospitalized at the time of randomization;
6. On 1000 mg of solumedrol per day for myocarditis or with an intent to initiate 1000 mg
of solumedrol per day for myocarditis within 24 hours of first administration of study
drug;
7. Serum evidence of ongoing myocardial injury: Serum evidence of ongoing myocardial
injury will be defined as an institutional troponin (either conventional or
high-sensitivity troponin I or T, using the standard institutional assay) with a value
that is ≥5 times the upper limit of the reference standard normal for that
institution. The troponin assay may be adjusted based on sex depending on
institutional standards. This value of troponin of ≥5 times above the institutional
upper limits of normal value must be noted within 10 days prior to potential
randomization. The 10-day period can be in the outpatient or inpatient setting. For
example, a participant with a troponin value that on one occasion was ≥5 times the
upper limits of institutional normal in the 10-day window prior to potential
randomization (whether in the inpatient or outpatient setting), but later decreases
below that threshold, typically due to starting corticosteroids, would still be
considered eligible;
8. The following laboratory parameters, not older than 48 hours at the time of
randomization, and measured as part of usual care:
• Total white blood cell (WBC) count >2,500/μl
• Absolute neutrophil count (ANC) >1,500/μL
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) <20 times the
upper limit of the institutional normal ranges;
9. Women of childbearing potential (i.e., not postmenopausal, or surgically sterilized)
must have a negative highly sensitive urine or serum pregnancy test prior to
randomization. Participating women of childbearing potential must be willing to
consistently use effective methods of contraception from screening until at least 90
days after administration of the last dose of study drug. Participating men must also
be willing to consistently use effective methods of contraception from screening until
at least 90 days after administration of the last dose of study drug; and
10. Must be willing and able to abide by all study requirements and restrictions.
Exclusion Criteria:
1. Must not have experienced any of the following (as defined in the section on the
primary endpoint) in the 30-day period prior to randomization:
• A sudden cardiac arrest
• Cardiogenic shock as defined. A significant bradyarrhythmia (Mobitz type II
second degree atrioventricular block or third degree (complete) atrio-ventricular
(AV) block, for which an intervention with a temporary or permanent pacemaker is
completed or recommended).
• A significant tachyarrhythmia (ventricular fibrillation of any duration or
sustained ventricular tachycardia (>30 seconds, >120 beats per minute); or a
ventricular tachyarrhythmia requiring intervention.
2. Recent (≤2 month) exposure to abatacept or belatacept.
3. Concurrent or recent (≤2 month) use of the following non-corticosteroid
immunosuppressive therapies prior to randomization: mycophenolate, JAK STAT inhibitors
(including but not limited to upadacitinib, tofacitinib, baricitinib, and filgotinib),
tacrolimus, anti-thymocyte globulin, alemtuzumab, infliximab, and plasma exchange. The
use of intravenous immunoglobulin is permitted prior to randomization and during study
treatment.
4. Currently enrolled in another interventional study utilizing systemic agents for the
management of ICI-related toxicities.
5. Female who is pregnant, breastfeeding, or is considering becoming pregnant during the
study or for approximately 90 days after the last dose of study drug.
6. Male who is considering fathering a child or donating sperm during the study or for
approximately 30 days after the last dose of study drug.
7. Any active, chronic, or recurrent viral infection that, based on the investigator's
clinical assessment, makes the participant an unsuitable candidate for the study.
These may include hepatitis B virus (HBV) or hepatitis C virus (HCV), recurrent or
disseminated (even a single episode) herpes zoster, and disseminated (even a single
episode) herpes simplex. Active HBV and HCV are defined as: HBV: hepatitis B surface
antigen (HBs Ag) positive (+) or detected sensitivity on the HBV deoxyribonucleic acid
(DNA) polymerase chain reaction (PCR) qualitative test for Hepatitis B core antibody
(HBc Ab) positive (+) participants; HCV: HCV ribonucleic acid (RNA) detectable in any
participant with anti-HCV antibody (HCV Ab). Patients with active Covid-19 infection
will be excluded. This is defined as the period of ongoing symptoms in the setting of
a positive Covid-19 test, or until 10 days after symptom onset and after resolution of
fever for at least 24 hours, without the use of fever-reducing medications.
8. Known active tuberculosis (TB), history of incompletely treated TB, suspected or known
extrapulmonary TB, suspected or known systemic bacterial or fungal infections;
9. Receipt of any live vaccine within four weeks prior to the first dose of study drug,
or expected need of live vaccination during study participation including at least 90
days after the last dose of IV study drug.
10. Any medical condition that could interfere with, or for which the treatment might
interfere with, the conduct of the study or interpretation of the study results, or
that would, in the opinion of the Investigator, increase the risk of the participant
by participating in the study.
11. Any factors that, in the Investigator's opinion, are likely to interfere with study
procedures, such as history of noncompliance with scheduled appointments.
Drug: Abatacept plus, Drug: Placebo
Cancer, Brain and Nervous System, Eye and Orbit, Anus, Bones and Joints, Breast - Female, Breast - Male, Cervix, Colon, Corpus Uteri, Esophagus, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung/Thoracic, Melanoma, skin, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Rectum, Stomach, Thyroid, Urinary Bladder, Small Intestine, Soft Tissue, Unknown Sites, Myocarditis Acute
A Study of Selpercatinib (LOXO-292) in Participants With Advanced Solid Tumors, RET Fusion-Positive Solid Tumors, and Medullary Thyroid Cancer (LIBRETTO-001) (LIBRETTO-001)
This is an open-label, first-in-human study designed to evaluate the safety, tolerability,
pharmacokinetics (PK) and preliminary anti-tumor activity of selpercatinib (also known as
LOXO-292) administered orally to participants with advanced solid tumors, including
rearranged during transfection (RET)-fusion-positive solid tumors, medullary thyroid cancer
(MTC) and other tumors with RET activation.
For Phase 1:
• Participants with a locally advanced or metastatic solid tumor that:
• Has progressed on or is intolerant to standard therapy, or
• For which no standard therapy exists, or in the opinion of the Investigator, are not
candidates for or would be unlikely to tolerate or derive significant clinical benefit
from standard therapy, or
• Decline standard therapy
• Prior multikinase inhibitors (MKIs) with anti-RET activity are allowed
• A RET gene alteration is not required initially. Once adequate PK exposure is
achieved, evidence of RET gene alteration in tumor and/or blood is required as
identified through molecular assays, as performed for clinical evaluation
• Measurable or non-measurable disease as determined by RECIST 1.1 or RANO as
appropriate to tumor type
• Eastern Cooperative Oncology Group (ECOG) score of 0, 1, or 2 or Lansky Performance
Score (LPS) greater than or equal to (≥) 40 percent (%) (age less than [<] 16 years)
with no sudden deterioration 2 weeks prior to the first dose of study treatment
• Adequate hematologic, hepatic and renal function
• Life expectancy of at least 3 months
For Phase 2: As for phase 1 with the following modifications:
• For Cohort 1: Participants must have received prior standard therapy appropriate for
their tumor type and stage of disease, or in the opinion of the Investigator, would be
unlikely to tolerate or derive clinical benefit from appropriate standard of care
therapy
• Cohorts 1 and 2:
• Enrollment will be restricted to participants with evidence of a RET gene
alteration in tumor
• At least one measurable lesion as defined by RECIST 1.1 or RANO, as appropriate
to tumor type and not previously irradiated
• Cohorts 3 and 4: Enrollment closed
• Cohort 5:
• Cohorts 1-4 without measurable disease
• MCT not meeting the requirements for Cohorts 3 or 4
• MTC syndrome spectrum cancers (e.g., MTC, pheochromocytoma), cancers with
neuroendocrine features/differentiation, or poorly differentiated thyroid cancers
with other RET alteration/activation may be allowed with prior Sponsor approval
• cfDNA positive for a RET gene alteration not known to be present in a tumor
sample
• Cohort 6: Participants who otherwise are eligible for Cohorts 1, 2 or 5 who
discontinued another RET inhibitor may be eligible with prior Sponsor approval
• Cohort 7: Participants with a histologically confirmed stage IB-IIIA NSCLC and a RET
fusion; determined to be medically operable and tumor deemed resectable by a thoracic
surgical oncologist, without prior systemic treatment for NSCLC
Key Exclusion Criteria (Phase 1 and Phase 2):
• Phase 2 Cohorts 1 and 2: an additional known oncogenic driver
• Cohorts 3 and 4: Enrollment closed
• Cohorts 1, 2 and 5: prior treatment with a selective RET inhibitor Notes: Participants
otherwise eligible for Cohorts 1, 2, and 5 who discontinued another selective RET
inhibitor may be eligible for Phase 2 Cohort 6 with prior Sponsor approval
• Investigational agent or anticancer therapy (including chemotherapy, biologic therapy,
immunotherapy, anticancer Chinese medicine or other anticancer herbal remedy) within 5
half-lives or 2 weeks (whichever is shorter) prior to planned start of LOXO-292
(selpercatinib). In addition, no concurrent investigational anti-cancer therapy is
permitted Note: Potential exception for this exclusion criterion will require a valid
scientific justification and approval from the Sponsor
• Major surgery (excluding placement of vascular access) within 2 weeks prior to planned
start of LOXO-292 (selpercatinib)
• Radiotherapy with a limited field of radiation for palliation within 1 week of planned
start of LOXO-292 (selpercatinib), with the exception of participants receiving
radiation to more than 30% of the bone marrow or with a wide field of radiation, which
must be completed at least 4 weeks prior to the first dose of study treatment
• Any unresolved toxicities from prior therapy greater than Common Terminology Criteria
for Adverse Events (CTCAE) Grade 1 at the time of starting study treatment with the
exception of alopecia and Grade 2, prior platinum-therapy related neuropathy
• Symptomatic primary CNS tumor, metastases, leptomeningeal carcinomatosis, or untreated
spinal cord compression. Participants are eligible if neurological symptoms and CNS
imaging are stable and steroid dose is stable for 14 days prior to the first dose of
LOXO-292 (selpercatinib) and no CNS surgery or radiation has been performed for 28
days, 14 days if stereotactic radiosurgery (SRS)
• Clinically significant active cardiovascular disease or history of myocardial
infarction within 6 months prior to planned start of LOXO-292 (selpercatinib) or
prolongation of the QT interval corrected (QTcF) greater than (>) 470 milliseconds
(msec)
• Participants with implanted pacemakers may enter the study without meeting QTc
criteria due to nonevaluable measurement if it is possible to monitor for QT
changes.
• Participants with bundle branch block may be considered for study entry if QTc is
appropriate by a formula other than Fridericia's and if it is possible to monitor
for QT changes.
• Required treatment with certain strong cytochrome P450 3A4 (CYP3A4) inhibitors or
inducers and certain prohibited concomitant medications
• Phase 2 Cohort 7 (neoadjuvant treatment): Participant must not have received prior
systemic therapy for NSCLC.
Drug: LOXO-292
Lymphoma, Non-Small Cell Lung Cancer, Colon Cancer, Medullary Thyroid Cancer, Any Solid Tumor, Brain and Nervous System, Eye and Orbit, Anus, Bones and Joints, Breast - Female, Breast - Male, Cervix, Colon, Corpus Uteri, Esophagus, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung/Thoracic, Melanoma, skin, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Stomach, Thyroid, Urinary Bladder, Hodgkins Lymphoma, Small Intestine, Soft Tissue
LOXO-292, KIF5B-RET, M918T, CCDC6-RET, RET-PTC1, NCOA4-RET, RET-PTC, RET-PTC3, RET-PTC4, PRKAR1A-RET, RET-PTC2, GOLGA5-RET, RET-PTC5, ERC1-RET, KTN1-RET, RET-PTC8, HOOK3-RET, PCM1-RET, TRIM24-RET, RET-PTC6, TRIM27-RET, TRIM33-RET, RET-PTC7, AKAP13-RET, FKBP15-RET, SPECC1L-RET, TBL1XR1-RET, BCR-RET, FGRF1OP-RET, RFG8-RET, RET-PTC9, ACBD5-RET, MYH13-RET, CUX1-RET, KIAA1468-RET, FRMD4A-RET, SQSTM1-RET, AFAP1L2-RET, PPFIBP2-RET, EML4-RET, PARD3-RET, G533C, C609F, C609G, C609R, C609S, C609Y, C611F, C611G, C611S, C611Y, C611W, C618F, C618R, C618S, C620F, C620R, C620S, C630R, C630Y, D631Y, C634F, C634G, C634R, C634S, C634W, C634Y, K666E, E768D, L790F, V804L, V804M, A883F, S891A, R912P, CLIP1-RET, Y806C, RET fusion, RET alteration, RET mutation, RET rearrangement, RET translocation, Neoplasms by Site, Neoplasms, Non-Small Cell Lung Cancer, Lung Neoplasms, Carcinoma, Non-Small-Cell Lung, Cancer of Lung, Cancer of the Lung, Lung Cancer, Neoplasms, Lung, Neoplasms, Pulmonary, Pulmonary Cancer, Pulmonary Neoplasms, Respiratory Tract Neoplasms, Lung Diseases, Respiratory Tract Diseases, Carcinoma, Bronchogenic, Bronchial Neoplasms, Medullary Thyroid Cancer, Papillary Thyroid Cancer, Thyroid Diseases, Thyroid Neoplasms, Cancer of the Thyroid, Cancer of Thyroid, Neoplasms, Thyroid, Thyroid Ademona, Thyroid Cancer, Thyroid Carcinoma, Endocrine System Diseases, Endocrine Gland Neoplasms, Head and Neck Neoplasms, Thoracic Neoplasms, CNS tumor, Primary CNS tumor, Cancer of Colon, Cancer of the Colon, Colon Cancer, Colon Neoplasms, Colonic Cancer, Neoplasms, Colonic, Malignant tumor of Breast, Mammary Cancer, Mammary Carcinoma, Human, Mammary Neoplasm, Human, Neoplasms, Breast, Tumors, Breast, Human Mammary Carcinoma, Malignant Neoplasm of Breast, Breast Carcinoma, Breast Tumors, Cancer of the Breast, Breast Neoplasms, Breast Cancer, RET Inhibitor, MTC, NSCLC, selpercatinib, neo-adjuvant treatment in early stage NSCLC
A Study of LOXO-783 in Patients With Breast Cancer/Other Solid Tumors (PIKASSO-01)
The main purpose of this study is to learn more about the safety, side effects, and
effectiveness of LOXO-783. LOXO-783 may be used to treat breast cancer and other solid tumors
that have a change in a particular gene (known as the PIK3CA gene). Participation could last
up to 36 months (3 years) and possibly longer if the disease does not get worse.
• Have advanced breast cancer or another solid tumor with the presence of a PIK3CA
H1047R mutation (or other Sponsor and SRC-approved, activating PIK3CA mutations other
than H1047R mutation)
• Have adequate archival tumor tissue sample available or be approved by the Sponsor for
enrollment if no tumor sample is available.
• Have stopped all cancer treatment and have recovered from the major side effects
• Have adequate organ function, as measured by blood tests
• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)
scale
• Patients must have
• Measurable disease
--- Patients with non-breast tumor types must have at least 1 measurable lesion
• Non-measurable bone disease (at least one bone lesion in breast cancer patients
only)
• For patients with an ER+ breast cancer diagnosis:
• If female, must be postmenopausal
• If male, must agree to use hormone suppression
• Phase 1a:
-- Dose escalation and backfill patients:
• Advanced solid tumor
• Patients may have had up to 5 prior regimens for advanced disease
• Phase 1b:
• Part A:
• ER+/HER2- advanced breast cancer
• Patients may have had up to 2 prior regimens for advanced disease
• Prior cyclin dependent kinase (CDK)4/6 inhibitor therapy required
• Part B:
• ER+/HER2- advanced breast cancer
• Patients may have had up to 2 prior regimens for advanced disease.
• Part C:
• ER+/HER2- advanced breast cancer
• Patients may have had up to 5 prior regimens for advanced disease.
---- Prior CDK4/6 inhibitor therapy required.
• Have a diagnosis of diabetes mellitus Type 2
• Part D:
• Advanced breast cancer
• Patients may have had up to 5 prior regimens for advanced disease.
• Part E:
• Advanced solid tumor
• Patients may have had up to 3 prior regimens for advanced disease
Exclusion Criteria:
• Medical Conditions
• Colorectal cancer
• Endometrial cancers with specific concurrent oncogenic alterations
• A history of known active or suspected
• Diabetes mellitus Type 1 or
• Diabetes mellitus Type 2 requiring antidiabetic medication (Phase 1a and all
parts of Phase 1b except Part C).
• Serious concomitant systemic disorder
• Known or suspected history of untreated or uncontrolled central nervous system (CNS)
involvement.
• Active uncontrolled systemic bacterial, viral, fungal, or parasitic infection, or
other clinically significant active disease process
• Prior exposure to PI3K/AKT/mTOR inhibitor(s), except in certain circumstances
Breast Cancer, Brain and Nervous System, Eye and Orbit, Anus, Bones and Joints, Breast - Female, Breast - Male, Cervix, Colon, Corpus Uteri, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung/Thoracic, Melanoma, skin, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Rectum, Stomach, Thyroid, Kaposis sarcoma, Small Intestine, Soft Tissue, Unknown Sites
The iCat2, GAIN (Genomic Assessment Informs Novel Therapy) Consortium Study
This research study is evaluating the use of specialized testing of solid tumors including
sequencing. The process of performing these specialized tests is called tumor profiling. The
tumor profiling may result in identifying changes in genes of the tumor that indicate that a
particular therapy may have activity. This is called an individualized cancer therapy (iCat)
recommendation. The results of the tumor profiling and, if applicable, the iCat
recommendation will be returned.
• Age -- Age ≤ 30 years at time of initial qualifying solid tumor diagnosis
• Diagnosis -- Histologic diagnosis of solid malignancy (excluding brain tumors and
lymphoma) that meets at least one of the following criteria:
• Refractory, defined as tumor progression after initiation of standard first line
therapy without having achieved a prior partial or complete remission OR Biopsy
proven residual disease at the completion of planned standard initial front-line
therapy.
• Recurrent, defined as tumor progression after achieving a prior partial or
complete remission
• Newly diagnosed high risk disease, defined as having an expected event free
survival of < 50% at 2 years.
• Lacks definitive diagnosis or classical genomic findings after histologic review
and standard molecular testing (rare tumor group).
• Examples include (eligibility not limited to these examples):
• Histology typically associated with a fusion in which fusion is not detected.
• Ewing-like sarcoma
• Undifferentiated sarcoma
• Inflammatory myofibroblastic tumor without ALK fusion
• Infantile fibrosarcoma without NTRK fusion
• Specimen Samples
• Sufficient tumor specimen available to meet the minimum requirements for
profiling from diagnosis or progression / recurrence
--- OR
• Surgery / biopsy planned as part of clinical care that is anticipated to yield
sufficient material to meet the minimum requirements for profiling; OR
• Patient has already had molecular profiling and patient has not yet started
matched targeted therapy based on the report .
Exclusion Criteria:
• No Therapy Planned
-- Patients who have declined further anticancer therapy will be excluded.
• Performance Status
-- Patients with Lansky (age < 16 years) or Karnofsky (age ≥16 years) score < 50 will
be excluded.
• Life Expectancy -- Patients with anticipated life expectancy < 3 months will be
excluded.
Genetic: Genetic testing and GAIN report
Sarcoma, Pediatric Solid Tumor, Brain and Nervous System, Other, Eye and Orbit, Anklylosing Spondylitis, Anus, Bones and Joints, Breast - Female, Breast - Male, Carcinoid Tumor, Cervix, Colon, Corpus Uteri, Ear, Esophagus, Gall Bladder, Head and Neck, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung/Thoracic, Melanoma, skin, Nose, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Rectum, Stomach, Throat, Thyroid, Urinary Bladder, Uterine (Endometrial), Vulva, Heart, Kaposis sarcoma, Small Intestine, Soft Tissue, Ill - Defined Sites
Phase 1 Dose-escalating Study of MM-398 (Irinotecan Sucrosofate Liposome Injection) Plus Intravenous Cyclophosphamide in Recurrent or Refractory Pediatric Solid Tumors
This is a Phase 1 study of the combination of two drugs: MM-398 and Cyclophosphamide. The
goal is to find the highest dose of MM-398 that can be given safely when it is used together
with the chemotherapy drug Cyclophosphamide.
• Histologically or cytologically-confirmed Ewing sarcoma, rhabdomyosarcoma,
neuroblastoma, or osteosarcoma
• Disease progression after prior therapy in locally advanced or metastatic setting
• Measurable or evaluable disease based on the Response Evaluation Criteria in Solid
Tumors (RECIST v1.1) criteria
• Age 12 months to <21 years
• Adequate bone marrow reserves, hepatic function, and renal function
• Recovered from effects of any prior surgery or cancer therapy
• Patients 18 years or older will provide written consent. A parent or legal guardian of
a patient <18 years of age will provide informed consent and patients 11 to 18 years
of age will provide written assent or as per participating institutional policy.
Exclusion Criteria:
• Clinically significant gastrointestinal disorders
• NYHA Class III or IV congestive heart failure, ventricular arrhythmias or uncontrolled
blood pressure
• Active infection or unexplained fever
• Known hypersensitivity to any of the components of MM-398 or other liposomal products
• Recent Investigational therapy
• Pregnant or breast feeding; females of child-bearing potential must test negative for
pregnancy at the time of enrollment
Drug: MM-398 (Irinotecan Sucrosofate Liposome Injection) plus cyclophosphamide
Neuroblastoma, Sarcoma, Ewing Sarcoma, Mycosis Fungoides, Rhabdomyosarcoma, Osteosarcoma, Recurrent or Refractory Solid Tumors, Brain and Nervous System, Eye and Orbit, Anus, Bones and Joints, Breast - Female, Breast - Male, Cervix, Colon, Corpus Uteri, Ear, Esophagus, Gall Bladder, Head and Neck, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung/Thoracic, Melanoma, skin, Nose, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Rectum, Stomach, Throat, Thyroid, Urinary Bladder, Uterine (Endometrial), Vulva, Hodgkins Lymphoma, Kaposis sarcoma, Other Hematopoietic, Small Intestine, Soft Tissue
Testicular Tissue Cryopreservation for Fertility Preservation
Testicular tissue cryopreservation is an experimental procedure where a young boy's
testicular tissue is retrieved and frozen. This technique is reserved for young male patients
who are not yet producing mature sperm, with the ultimate goal that their tissue may be used
in the future to restore fertility when experimental techniques emerge from the research
pipeline.
• Be male at any age.
• Be scheduled to undergo surgery, chemotherapy, drug treatment and/or radiation for the
treatment or prevention of a medical condition or malignancy with risk of causing
permanent and complete loss of subsequent testicular function.
• Or, have a medical condition or malignancy that requires removal of all or part of one
or both testicles.
• Have newly diagnosed or recurrent disease. Those who were not enrolled at the time of
initial diagnosis (i.e., patients with recurrent disease) are eligible if they have
not previously received therapy that is viewed as likely to result in complete and
permanent loss of testicular function.
• Have two testicles if undergoing elective removal of all or part of a testicle for
fertility preservation only. Note: removal of both testicles will limit fertility
preservation options.
• Sign an approved informed consent and authorization permitting the release of personal
health information. The patient and/or the patient's legally authorized guardian must
acknowledge in writing that consent for specimen collection has been obtained, in
accordance with institutional policies approved by the U.S. Department of Health and
• Consent for serum screening tests for infectious diseases [HIV-1, HIV-2, Hepatitis B,
Hepatitis C], to be performed at the time of testicular tissue harvesting.
• Undergo a full history and physical examination and obtain standard pre-operative
clearance (based on the most recent ACC/AHA Guideline for Perioperative Cardiovascular
Evaluation for Noncardiac Surgery) as determined by their primary surgeon.
• Participating in long term follow-up is a requirement of the protocol.
Exclusion Criteria:
• Diagnosed with psychological, psychiatric, or other conditions which prevent giving
fully informed consent.
• Diagnosed with an underlying medical condition that significantly increases their risk
of complications from anesthesia and surgery.
Procedure: Testicular biopsy
Lymphoma, Sarcoma, Cancer, Mycosis Fungoides, Brain and Nervous System, Other, Eye and Orbit, Anklylosing Spondylitis, Anus, Bones and Joints, Breast - Male, Carcinoid Tumor, Cardiovascular, Colon, Esophagus, Gall Bladder, Head and Neck, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung/Thoracic, Nose, Other Digestive Organ, Other Endocrine System, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Pancreas, Prostate, Rectum, Stomach, Throat, Thyroid, Urinary Bladder, Leukemia, Other, Hodgkins Lymphoma, Heart, Leukemia, Not Otherwise Specified, Lymphoid Leukemia, Myeloid and Monocytic Leukemia, Non-Hodgkins Lymphoma, Other Hematopoietic, Small Intestine, Soft Tissue, Unknown Sites, Ill - Defined Sites, Autoimmune Disorders
Stereotactic Radiosurgery (SRS) Dose-Escalation Study for Brain Metastasis (SRS)
SRS dose escalation for brain metastases in radiation-naïve patients will establish true
tolerable doses, which may exceed the current standard doses. This may lead to an improvement
in local control, patient survival, and/or quality-of life.
Inclusion Criteria
1. Biopsy-proven non-hematopoietic malignancy, except for small cell lung cancer, germ
cell cancer, or unknown primary tumor.
2. Radiographic evidence by MRI (or by CT scan with CT contrast if ineligible or
intolerant of MRI) of brain metastasis. (If patient is unable to tolerate MRI
contrast, an MRI without contrast is acceptable if lesions are visible)
3. All brain metastases must be outside the brain stem (midbrain, pons and medulla).
4. Patient must have 10 or less brain metastases.
5. The maximum diameter of any lesion must be less than or equal to 3.0 cm.
6. Previous treatment with surgery, radiation, chemotherapy, immunotherapy or any
targeted agents are allowed provided that:
• Radiation was not to the brain.
• Surgery to the brain was > 7 days prior to SRS and there remains at least one
additional brain metastasis that can be targeted with SRS
7. Age ≥ 18 years.
8. ECOG Performance Score of 2 or better/Karnofsky Performance Status score of 50-60 or
better.
9. All men, as well as women of child-bearing potential must agree to use adequate
contraception (hormonal or barrier method of birth control; abstinence) prior to study
entry and for the duration of study participation. Should a woman become pregnant or
suspect she is pregnant while participating in this study, she should inform her
treating physician immediately.
A female of child-bearing potential is any woman (regardless of sexual orientation,
marital status, having undergone a tubal ligation, or remaining celibate by choice)
who meets the following criteria:
• Has not undergone a hysterectomy or bilateral oophorectomy; or
• Has not been naturally postmenopausal for at least 12 consecutive months (i.e.,
has had menses at any time in the preceding 12 consecutive months).
Medically acceptable birth control (contraceptives) includes:
• Approved hormonal contraceptives (such as birth control pills, patch, or ring:
Depo-Provera, Implanon), or
• Barrier methods (such as a condom or diaphragm) used with a spermicide (a
substance that kills sperm)
10. Ability to understand and the willingness to sign a written informed consent.
Exclusion Criteria
1. Patients had craniotomy and surgery to the brain within 7 days from the date of SRS.
2. Patients with leptomeningeal metastasis.
NOTE: For the purposes of exclusion, LMD is a clinical diagnosis, defined as positive
CSF cytology and/or equivocal radiologic or clinical evidence of leptomeningeal
involvement. Patients with leptomeningeal symptoms in the setting of leptomeningeal
enhancement by imaging (MRI) would be considered to have LMD even in the absence of
positive CSF cytology, unless a parenchymal lesion can adequately explain the
neurologic symptoms and/or signs. In contrast, an asymptomatic or minimally
symptomatic patient with mild or nonspecific leptomeningeal enhancement (MRI) would
not be considered to have LMD. In that patient, CSF sampling is not required to
formally exclude LMD, but can be performed at the investigator's discretion based on
level of clinical suspicion.
3. Patients with a contraindication to both MRI (with or without contrast) and CT scan
(with contrast)
4. Patients with life expectancy < 3 months.
5. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that, in the opinion of the
investigator, would limit compliance with study requirements.
6. Subjects must not be pregnant or nursing at the time of SRS treatment due to the
potential for congenital abnormalities and the potential of this regimen to harm
nursing infants.
Radiation: Stereotactic Radiosurgery
Brain Neoplasms, Adult, Malignant, Lymphoma, Sarcoma, Multiple Myeloma, Brain and Nervous System, Other, Eye and Orbit, Anklylosing Spondylitis, Anus, Bones and Joints, Breast - Female, Breast - Male, Cardiovascular, Cervix, Colon, Corpus Uteri, Ear, Esophagus, Gall Bladder, Head and Neck, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung/Thoracic, Melanoma, skin, Nose, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Rectum, Stomach, Throat, Thyroid, Urinary Bladder, Uterine (Endometrial), Vulva, Hodgkins Lymphoma, Lymphoid Leukemia, Small Intestine, Soft Tissue
UT Southwestern; Parkland Health & Hospital System
Study Of Palbociclib Combined With Chemotherapy In Pediatric Patients With Recurrent/Refractory Solid Tumors
A study to learn about safety and find out maximum tolerable dose of palbociclib given in
combination with chemotherapy (temozolomide with irinotecan or topotecan with
cyclophosphamide) in children, adolescents and young adults with recurrent or refractory
solid tumors (phase 1). Phase 2 to learn about the efficacy of palbociclib in combination
with irinotecan and temozolomide when compared with irinotecan and temozolomide alone in the
treatment of children, adolescents, and young adults with recurrent or refractory Ewing
sarcoma (EWS).
Inclusion:
1. Histologically confirmed relapsed or refractory solid tumor as follows:
• For dose escalation and dose determination parts: Histologically confirmed
relapsed or refractory solid tumor (including CNS tumors but not lymphomas).
Patients with Diffuse Intrinsic Pontine Glioma do not require histological only
radiographic confirmed relapse to enroll.
• For dose expansion and tumor specific cohorts: Histologically confirmed relapsed
or refractory solid tumor including but not limited to EWS, rhabdoid tumor,
rhabdomyosarcoma, neuroblastoma, and medulloblastoma. Patients with Diffuse
Intrinsic Pontine Glioma do not require histological only radiographic confirmed
relapse to enroll. EWS is not eligible for TOPO and CTX tumor-specific cohorts.
• For randomized Phase 2 part: Histologically confirmed Ewing sarcoma at diagnosis
or at relapse, with presence of EWSR1-ETS or FUS-ETS rearrangement.
Histopathology confirmation of both EWSR1-ETS or FUS-ETS rearrangement partners
is required OR availability of formalin fixed paraffin embedded (FFPE) tumor
tissue sample for central testing. Patient must have relapsed or have refractory
disease and at least evaluable disease in at least one site other than bone
marrow that can be followed by imaging.
2. Age ≥2 and <21 years at the time of study entry.
3. Lansky performance status ≥50% for patients ≤16 years of age, or Eastern Cooperative
Oncology Group (ECOG) 0, 1 or 2 for patients >16 years of age.
4. Adequate bone marrow function.
• Absolute neutrophil count ≥1000/mm3;
• Platelet count ≥100,000/mm3 (transfusion independent, no platelet transfusion in
past 7 days prior study entry);
• Hemoglobin ≥8.5 g/dL (transfusion allowed).
5. Adequate renal function: Serum creatinine level based on age/gender must within
protocol specified limits.
6. Adequate liver function, including:
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT)
≤2.5 × upper limit of normal (ULN) or ≤5 × ULN for age, if attributable to
disease involvement of the liver;
• Total bilirubin ≤1.5 × ULN for age, unless the patient has documented Gilbert's
syndrome.
7. Patients enrolled to Phase 1 portion of the study and tumor specific cohorts must have
measurable disease as defined by RECIST version 1.1 or modified RANO criteria for CNS
disease or INRC for neuroblastoma. Patients with EWS enrolled to Phase 2 portion of
the study are eligible with evaluable disease (eg, bone only disease with no soft
tissue component).
8. Recovered to CTCAE Grade ≤1, or to baseline, from any non-hematological acute
toxicities of prior surgery, chemotherapy, immunotherapy, radiotherapy,
differentiation therapy or biologic therapy, with the exception of alopecia.
9. Serum/urine pregnancy test (for all girls ≥8 years of age) negative at screening and
at the baseline visit.
Exclusion:
1. Phase 1 and tumor specific cohorts: For palbociclib with IRN and TMZ combination,
prior treatment with a CDK4/6 inhibitor or progression while on treatment with an
IRN-containing regimen that includes TMZ. Patients who have received the combination
of IRN and TMZ and did not progress while on these medications are eligible. For
patients enrolling in the palbociclib with TOPO and CTX combination, prior treatment
with a CDK4/6 inhibitor or progression while on treatment with a TOPO-containing
regimen that includes CTX. Patients who have received the combination of TOPO and CTX
and did not progress while on these medications are eligible. Phase 2 portion: prior
treatment with a CDK4/6 inhibitor or progression while on treatment with an
IRN-containing or TMZ-containing regimen. Patients who have received IRN and/or TMZ
and did not progress while on these medications are eligible.
2. Prior intolerability to IRN and/or TMZ plus/minus palbociclib with IRN and TMZ
combination and prior intolerability to TOPO and/or CTX for TOPO and CTX combination.
3. Use of strong cytochrome P450 (CYP) 3A inhibitors or inducers. Patients who are
receiving strong uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1) inhibitors
within 12 days of Cycle 1 Day 1 (C1D1) are not eligible for the palbociclib with IRN
and TMZ combination. Patients who are receiving strong UGT1A1 inhibitors within 12
days of C1D1 are eligible for the palbociclib with TOPO and CTX combination (See
Section 5.7.1 for list of products.)
4. Systemic anti cancer therapy within 2 weeks prior to study entry and 6 weeks for
nitrosoureas.
5. Prior irradiation to >50% of the bone marrow (see Appendix 9).
6. Participation in other studies involving investigational drug(s) within 2 weeks or 5
half lives, whichever is longer, prior to study entry.
7. Major surgery within 4 weeks prior to study entry. Surgical biopsies or central line
placement are not considered major surgeries.
8. For IRN and TMZ with/without palbociclib combinations: known or suspected
hypersensitivity to palbociclib, IRN and/or TMZ. For combination of palbociclib with
TOPO and CTX: known or suspected hypersensitivity to palbociclib, TOPO and/or CTX.
9. Patients with known symptomatic brain tumors or brain metastases and require steroids,
unless they have been on a stable or on a decreasing steroid dose for >14 days.
10. Patients with previously diagnosed brain metastases are eligible if they have
completed their prior treatment and have recovered from the acute effects of radiation
therapy or surgery prior to study entry for these metastases for at least 14 days post
radiation and 4 weeks post-surgery and are neurologically stable.
11. Hereditary bone marrow failure disorder.
12. QTc >470 msec.
13. History of clinically significant or uncontrolled cardiac disease, including:
• History of or active congestive heart failure; if patient had congestive heart
failure resolve and >1 year from resolution, patient will be considered eligible;
• Clinically significant ventricular arrhythmia (such as ventricular tachycardia,
ventricular fibrillation or Torsades de Pointes);
• Diagnosed or suspected congenital or acquired prolonged QT syndrome;
• Need for medications known to prolong the QT interval;
• Uncorrected hypomagnesemia or hypokalemia because of potential effects on the QT
interval;
• Left ventricular ejection fraction <50% or shortening fraction <28%.
14. Recent or ongoing clinically significant gastrointestinal disorder that may interfere
with absorption of orally administered drugs (eg, gastrectomy).
15. Severe acute or chronic medical or laboratory test abnormality that may increase the
risk associated with study participation or investigational product administration or
may interfere with the interpretation of study results, and in the judgment of the
Investigator, would make the patient inappropriate for entry into this study.
16. Investigator site staff members directly involved in the conduct of the study and
their family members, site staff members otherwise supervised by the investigator, or
patients who are Pfizer employees, including their family members, directly involved
in the conduct of the study.
Neuroblastoma, Sarcoma, Solid Tumors, Ewing Sarcoma, Medulloblastoma, Diffuse Intrinsic Pontine Glioma, Rhabdomyosarcoma, Rhabdoid Tumor, Brain and Nervous System, Eye and Orbit, Anus, Bones and Joints, Breast - Female, Breast - Male, Cervix, Colon, Corpus Uteri, Ear, Esophagus, Gall Bladder, Head and Neck, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung/Thoracic, Nose, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Rectum, Stomach, Throat, Thyroid, Urinary Bladder, Uterine (Endometrial), Vulva, Kaposis sarcoma, Small Intestine, Soft Tissue, Ill - Defined Sites
Nivolumab in Treating Patients With Autoimmune Disorders and Advanced, Metastatic, or Unresectable Cancer
This phase Ib trial studies the side effects of nivolumab and to see how well it works in
treating patients with autoimmune disorders and cancer that has spread to other places in the
body or cannot removed by surgery. Immunotherapy with monoclonal antibodies, such as
nivolumab, may help the body's immune system attack the cancer, and may interfere with the
ability of tumor cells to grow and spread.
• Patients can have either histologically confirmed malignancy that is radiologically
evaluable and metastatic or unresectable, or have a malignancy for which a PD-1/PD-L1
inhibitor has been approved in the adjuvant setting. Eligible tumor types include
solid tumors and malignancies in which there is known evidence of clinical activity
for single agent PD-1 or PD-L1 antibodies. Nivolumab is Food and Drug Administration
(FDA)-approved for the treatment of melanoma, non-small cell lung cancer (NSCLC),
Merkel cell cancer, bladder cancer, renal cell carcinoma (RCC), gastric cancer,
hepatocellular carcinoma (HCC), cervical cancer, head and neck cancer, Hodgkin
lymphoma (HL), metastatic small cell lung cancer (SCLC), and any solid tumor with
microsatellite instability (MSI)-high status confirmed. Patients with HL are eligible
but must follow standard response criteria. Additional tumor types may be eligible on
a case by case basis upon discussion with principal investigator (PI). Patients
enrolling on the trial for adjuvant use will be restricted to those with histology for
which a PD-1/PD-L1 inhibitor has been approved in the adjuvant setting including but
not limited to NSCLC, melanoma, RCC, cervical cancer, and bladder cancer
• Patients who have previously received other forms of immunotherapy (high-dose [HD]
IL-2, IFN, CTLA-4) are allowed. Patients must not have received cytokine immunotherapy
for at least 4 weeks before nivolumab administration. Patients who have received prior
anti-CTLA4 will be allowed and the washout period is 6 weeks
• Age >= 18 years; children are excluded from this study but may be eligible for future
pediatric phase 1 combination trials
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 (Karnofsky >=
60)
• Life expectancy of greater than 12 weeks
• Leukocytes >= 1,000/mcL
• Absolute neutrophil count >= 500/mcL
• Platelets >= 50,000/mcL
• Total bilirubin =< 2 x institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
=< 5 x institutional ULN or < 8 x institutional ULN for patients with liver metastases
or an autoimmune disease that is contributing to the elevation of these values
• Creatinine ULN OR glomerular filtration rate (GFR) >= 30 mL/min (if using the
Cockcroft-Gault formula)
• Human immunodeficiency virus (HIV)-infected patients on effective antiretroviral
therapy with undetectable viral load within 6 months are eligible for this trial
• If evidence of chronic hepatitis B virus (HBV) infection, HBV viral load must be
undetectable on suppressive therapy if indicated
• If history of hepatitis C virus (HCV) infection, must be treated with undetectable HCV
viral load
• Patients with new or progressive brain metastases (active brain metastases) or
leptomeningeal disease are eligible if the treating physician determines that
immediate central nervous system (CNS) specific treatment is not required and is
unlikely to be required for at least 4 weeks (or scheduled assessment after the first
cycle of treatment), and a risk-benefit analysis (discussion) by the patient and the
investigator favors participation in the clinical trial
• The effects of nivolumab on the developing human fetus are unknown. For this reason,
women of child-bearing potential (WOCBP) and men must agree to use adequate
contraception (hormonal or barrier method of birth control; abstinence) prior to study
entry and for the duration of study participation. WOCBP receiving nivolumab will be
instructed to adhere to contraception for a period of 5 months after the last dose of
investigational product. Men receiving nivolumab and who are sexually active with
WOCBP will be instructed to adhere to contraception for a period of 7 months after the
last dose of investigational product. Women of childbearing potential must have a
negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent
units of human chorionic gonadotropin [HCG]) within 24 hours prior to the start of
nivolumab. Women must not be breastfeeding. Women who are not of childbearing
potential (i.e., who are postmenopausal or surgically sterile as well as azoospermic
men) do not require contraception. WOCBP is defined as any female who has experienced
menarche and who has not undergone surgical sterilization (hysterectomy or bilateral
oophorectomy) or who is not postmenopausal. Menopause is defined clinically as 12
months of amenorrhea in a woman over 45 in the absence of other biological or
physiological causes. In addition, women under the age of 55 must have a documented
serum follicle stimulating hormone (FSH) level less than 40 mIU/mL. These durations
have been calculated using the upper limit of the half-life for nivolumab (25 days)
and are based on the protocol requirement that WOCBP use contraception for 5
half-lives plus 30 days, and men who are sexually active with WOCBP use contraception
for 5 half-lives plus 90 days. Should a woman become pregnant or suspect she is
pregnant while she or her partner is participating in this study, she (or the
participating partner) should inform the treating physician immediately
• Ability to understand and the willingness to sign a written informed consent document
• Patients with more than one autoimmune disease are eligible. The treating physician
would determine which autoimmune disease is dominant and the patient would be treated
under that specific cohort
Exclusion Criteria:
• Patients who have had chemotherapy or radiotherapy within 2 weeks (6 weeks for
nitrosoureas or mitomycin C) prior to entering the study or those who have not
recovered from adverse events (AEs) due to agents administered more than 4 weeks
earlier have not resolved or stabilized. Palliative (limited-field) radiation therapy
(RT) is permitted (2 week washout from start of treatment), if all of the following
criteria are met:
• Repeat imaging demonstrates no new sites of bone metastases
• The lesion being considered for palliative radiation is not a target lesion
• Patients with prior therapy with an anti-PD-1 or anti-PD-L1
• Patients with prior allogeneic hematologic transplant
• Patients who are receiving any other anticancer investigational agents
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements
• Patients who have had evidence of active or acute diverticulitis, intra-abdominal
abscess, gastrointestinal (GI) bleeding, obstruction, and abdominal carcinomatosis
which are known risk factors for bowel perforation should be evaluated for the
potential need for additional treatment before coming on study. For the IBD (UC and
CD) cohort, an endoscopic assessment, disease activity index, and disease specific
inclusion/exclusion criteria will substitute for these factors in determining
eligibility with the exception of abdominal carcinomatosis, which should prompt
further evaluation
Olanzapine Versus Megestrol Acetate for the Treatment of Loss of Appetite Among Advanced Cancer Patients
This phase III trial compares the effects of olanzapine versus megestrol acetate in treating
loss of appetite in patients with cancer that has spread to other places in the body
(advanced). Olanzapine may stimulate and increase appetite. This study aims to find out if
olanzapine is better than the usual approach (megestrol acetate) for stimulating appetite and
preventing weight loss.
• Women and men of reproductive potential should agree to use an appropriate method of
birth control throughout their participation in this study due to the teratogenic
potential of the therapy utilized in this trial. Appropriate methods of birth control
include abstinence, oral contraceptives, implantable hormonal contraceptives or double
barrier method (diaphragm plus condom)
• Diagnosis of advanced cancer
• Patient-reported 2-month weight loss of at least 5 pounds (2.3 kilograms) and/or
physician-estimated caloric intake of less than 20 calories/kilogram of body weight
per day
• The patient must perceive loss of appetite and/or weight as a problem; and have an
appetite score of 4 or worse on the "Please rate your appetite…." question that
requires a patient response on a 0-10 numeric rating scale
• Not receiving ongoing tube feedings or parenteral nutrition at the time of
registration
• Not currently using systemic adrenal steroids (with the exception of short-term
dexamethasone within 3 days of chemotherapy for control of chemotherapy side effects)
• No use of androgens, progesterone analogs, or other appetite stimulants within the
past month
• Patient should not have poorly controlled hypertension or congestive heart failure at
registration
• Patient should not have an obstruction of the alimentary canal, malabsorption, or
intractable vomiting (defined as vomiting more than 3 times per day over the preceding
week)
• Not currently using olanzapine for another medical condition or had previously used
olanzapine for chronic nausea or for any pre-existing psychotic disorder
• Patient should not have had a previous blood clot at any time in the past
• No history of poorly controlled diabetes
• No symptomatic leptomeningeal disease or known brain metastases as these patients may
have difficulty taking oral medications
• No history of hypersensitivity to olanzapine or megestrol acetate
• No COVID-19 infection in the past that, in the opinion of the treating physician, had
left patients with compromised taste, which has not resolved at the time of
registration
• Not pregnant and not nursing, because this study involves an investigational agent
whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn
are unknown. Therefore, for women of childbearing potential only, a negative urine or
serum pregnancy test done =< 14 days prior to registration is required
• Age >= 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2
• Estimated life expectancy of 3 months or longer
• Serum creatinine =< 2.0 mg/dL
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =< 3 x upper limit
of normal (ULN)
• Fasting glucose > 1410 mg/dl
• Granulocytes > 1000/hpf
• No treatment with another antipsychotic agent, such as risperidone, quetiapine,
clozapine, butyrophenone within 30 days of enrollment
• In order to complete the mandatory patient-completed measures, participants must be
able to speak and/or read English or Spanish. Sites seeking to enroll Spanish-speaking
patients should have access to Spanish speaking staff on site or through the use of a
translation service to be able to conduct the informed consent discussion in Spanish,
and to conduct the weekly phone calls
Exclusion Criteria:
• Psychiatric illness which would prevent the patient from giving informed consent
• Medical condition such as uncontrolled infection (including human immunodeficiency
virus [HIV]), uncontrolled diabetes mellitus or cardiac disease which, in the opinion
of the treating physician, would make this protocol unreasonably hazardous for the
patient
• Patients who cannot swallow oral formulations of the agents
• Patients with impaired decision-making capacity (such as with a diagnosis of dementia
or memory loss) are not eligible for this study
• No presence of a hormone-sensitive tumor, such as breast, endometrial, or prostate
cancer (this exclusion criterion is intended to circumvent any confounding
antineoplastic effects of megestrol acetate)
[18F]PT2385 PET/CT in Patients With Renal Cell Carcinoma
This is an exploratory study to assess [18F]PT2385 Positron Emission Tomography/Computed
Tomography (PET/CT) in patients with renal cell carcinoma (RCC). This is an open-label,
nontherapeutic trial. The main objective is to correlate hypoxia-inducible factor-2alpha
(HIF2α) levels as determined by an investigational [18F]PT2385 PET/CT scan with the levels on
subsequently obtained tissue by HIF2α immunohistochemistry (IHC). There will be three
cohorts. The first pre-surgical cohort will have [18F]PT2385 PET/CT prior to nephrectomy. The
uptake and retention on Positron Emission Tomography (PET), quantified as standardized uptake
value (SUV) max and mean, abbreviated SUV henceforth will be correlated with HIF2α levels by
IHC on the primary tumor. The second cohort will comprise patients with metastatic clear cell
renal carcinoma (ccRCC). SUV will be correlated with HIF2α levels measured by IHC on a biopsy
sample from a metastasis. Both low- and high-avidity sites will be biopsied and tracer uptake
correlated with HIF2α IHC. A third cohort will include patients with Von Hippel-Lindau (VHL)
syndrome and any of the following disease manifestations - RCC, central nervous system (CNS)
hemangioblastoma, and/or pancreatic neuroendocrine tumor(s). Investigational imaging will
evaluate HIF2α expression within a tumor type and across different tumor types. A biopsy is
encouraged but not mandatory for this cohort.
• Ability to understand and the willingness to sign a written informed consent that
includes study interventions (PET/CT and, if cohort 2, mandatory biopsy).
• Ability to lie still for a 30- to 60-minute PET/CT scan.
• One of the following:
1. Cohort 1. Patients with suspected RCC planned for surgery.
2. Cohort 2. Patients with metastatic ccRCC or VHL syndrome and RCC. Biopsy is
required (planned resection for treatment reasons of a metastatic site is
acceptable in lieu of the biopsy).
3. Cohort 3. Patients with VHL syndrome with RCC, CNS hemangioblastoma, and/or
pancreatic neuroendocrine tumor(s) planning to start belzutifan.
• Women of child-bearing potential must agree to undergo and have documented a negative
pregnancy test on the day of [18F]PT2385 administration. A female of child-bearing
potential is any woman (regardless of sexual orientation, having undergone a tubal
ligation, or celibate by choice) who meets the following criteria:
1. Has not undergone a hysterectomy or bilateral oophorectomy; or
2. Has not been naturally postmenopausal for at least 12 consecutive months (i.e.,
has had menses at any time in the preceding 12 consecutive months).
Exclusion Criteria:
• Uncontrolled severe and irreversible intercurrent illness or psychiatric
illness/social situations that would limit compliance with study requirements.
• Subjects must not be pregnant or nursing due to the potential for congenital
abnormalities and the potential of this regimen to harm nursing infants.
• Claustrophobia or other contraindications to PET/CT.
• Subjects must not weigh more than the maximum weight limit for the table for the
PET/CT scanner where the study is being performed (>200 kilograms or 440 pounds).
• For cohort 2 patients, lack of suitable sites for mandatory biopsy. For example,
patients with metastatic disease restricted to the lungs that would require
percutaneous biopsies with associated risk of bleeding and pneumothorax will be
excluded.