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.
Safety and Efficacy of Retifanlimab (INCMGA00012) Alone or in Combination With Other Therapies in Participants With Advanced or Metastatic Endometrial Cancer Who Have Progressed on or After Platinum-based Chemotherapy. (POD1UM-204)
This is a multicenter, open-label, nonrandomized, Phase 2 umbrella study of retifanlimab in
participants who have advanced or metastatic endometrial cancer that has progressed on or
after platinum-based chemotherapy. retifanlimab will be administered as monotherapy or in
combination with other immunotherapy or targeted agents.
• Ability to comprehend and willingness to sign a written ICF for the study. Women 18
years of age or older (or as applicable per local country requirements).
• Histologically confirmed diagnosis of advanced or metastatic endometrial cancer with
disease progression on or after treatment with at least 1 platinum-containing regimen
for advanced or metastatic disease.
• Groups A and B: Have not been previously treated with a PD-(L)1 inhibitor.
• Group A only: Tumor tissue tested as MSI-High
• Group B only: Tumor tissue tested as deficient MMR or an ultra-mutated POLE tumor.
• Group D only: Tumor tissue tested as having an FGFR 1,2,3 mutation or alteration
characterized as per protocol.
• Must have at least 1 measurable tumor lesion per RECIST v1.1.
• Willing to provide tumor tissue sample (fresh or archived).
• ECOG performance status 0 to 1.
• Willingness to avoid pregnancy.
Exclusion Criteria:
• Group A only: Histologically confirmed diagnosis of carcinosarcoma of the uterus.
• Histologically confirmed diagnosis of sarcoma of the uterus.
• Has disease eligible for potentially curative treatment.
• Receipt of anticancer therapy within 28 days of the first administration of study
treatment, with the exception of localized radiotherapy.
• Toxicity of prior therapy that has not recovered to ≤ Grade 1 or baseline unless
approved by the medical monitor.
• Groups C and D (combinations): limiting immune-related toxicity during prior
checkpoint inhibitor therapy.
• Has an active autoimmune disease requiring systemic immunosuppression with
corticosteroids (> 10 mg/day of prednisone or equivalent) or immunosuppressive drugs
within 14 days before the first dose of study treatment.
• Receiving chronic systemic steroids (> 10 mg/day of prednisone or equivalent):
• Known active CNS metastases and/or carcinomatous meningitis.
• Has known active hepatitis B or C.
• Has received a live vaccine within 28 days of the planned start of study treatment.
• Evidence of interstitial lung disease or active, noninfectious pneumonitis.
• Participants who are known to be HIV-positive with some protocol exceptions.
Testing the Combination of Olaparib and Durvalumab, Cediranib and Durvalumab, Olaparib and Capivasertib, and Cediranib Alone in Recurrent or Refractory Endometrial Cancer Following the Earlier Phase of the Study That Tested Olaparib and Cediranib in Comparison to Cediranib Alone, and Olaparib Alone
This phase II trial studies the effects of the combination of olaparib and durvalumab,
cediranib and durvalumab, olaparib and capivasertib, and cediranib alone in treating patients
with endometrial cancer that has come back (recurrent) or does not respond to treatment
(refractory). Olaparib, cediranib, and capivasertib may stop the growth of tumor cells by
blocking some of the enzymes needed for cell growth. Durvalumab is a monoclonal antibody that
may interfere with the ability of tumor cells to grow and spread. Testing the combinations
may lower the chance of endometrial cancer growing or spreading compared to usual care.
• Patients must have recurrent or persistent endometrial carcinoma, which is refractory
to curative therapy or established treatments; histologic confirmation of the original
primary tumor is required; patients with the following histologic epithelial cell
types are eligible: endometrioid adenocarcinoma, serous adenocarcinoma,
undifferentiated carcinoma, mixed epithelial carcinoma, adenocarcinoma not otherwise
specified (N.O.S.); NOTE: clear cell histology is excluded
• Patients must have evaluable disease as defined by Response Evaluation Criteria in
Solid Tumors (RECIST) 1.1 or non-measurable (detectable) disease
• Measurable disease is defined as at least one lesion that can be accurately
measured in at least one dimension (longest diameter to be recorded); each lesion
must be >= 10 mm when measured by computed tomography (CT), magnetic resonance
imaging (MRI) or caliper measurement by clinical exam; or >= 20 mm when measured
by chest x-ray; lymph nodes must be > 15 mm in short axis when measured by CT or
MRI; patients with measurable disease must have at least one "target lesion" to
be used to assess response on this protocol as defined by RECIST version 1.1;
tumors within a previously irradiated field will be designated as "non-target"
lesions unless progression is documented or a biopsy is obtained to confirm
persistence at least 90 days following completion of radiation therapy
• Non-measurable (detectable) disease in a patient is defined in this protocol as
one who does not have measurable disease but has at least one of the following
conditions:
• Ascites and/or pleural effusion attributed to tumor;
• Solid and/or cystic abnormalities on radiographic imaging that do not meet
RECIST 1.1 definitions for target lesions
• Patients must have signed an approved informed consent and authorization permitting
release of personal health information
• Patients must have had one prior chemotherapeutic regimen for management of
endometrial carcinoma; initial treatment may include chemotherapy, chemotherapy and
radiation therapy, and/or consolidation/maintenance therapy; chemotherapy administered
in conjunction with primary radiation as a radio-sensitizer WILL be counted as a
systemic chemotherapy regimen
• Patients are allowed to receive, but are not required to receive, one additional
cytotoxic regimen for management of recurrent or persistent disease according to the
following definition: cytotoxic regimens include any agent that targets the genetic
and/or mitotic apparatus of dividing cells, resulting in dose-limiting toxicity to the
bone marrow and/or gastrointestinal mucosa; Note: patients on this non-cytotoxic study
are allowed to receive one additional cytotoxic chemotherapy regimen for management of
recurrent or persistent disease, as defined above; however, patients are encouraged to
enroll on second-line non-cytotoxic studies prior to receiving additional cytotoxic
therapy
• Patients may have received non cytotoxic therapy including immunotherapy (1 prior line
in either upfront or recurrent setting) but excluding cediranib, olaparib, AZD5363
(capivasertib), durvalumab (MEDI4736), or the combination of lenvatinib and
pembrolizumab for the management of recurrent or persistent disease; prior hormonal
therapy is allowed; hormonal therapy for grade 1 endometrial cancers with low volume
or indolent disease is encouraged
• Bevacizumab, or one course of single-agent immune-checkpoint therapy, excluding
durvalumab (MEDI4736), is permitted prior to enrollment on this trial
• Body weight > 30 kg
• Age >= 18
• The trial is open to females only (including women with an intact uterus with uterine
cancer); fertile females of childbearing potential need to agree to use adequate
contraceptive measures from 2 weeks prior to the study and until 1 month after study
treatment discontinuation, and have a negative serum or urine pregnancy test within 3
days prior to the start of study treatment
• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of
0,1 or 2 (Karnofsky >= 60%) within 7 days prior to registration; patients should have
no deterioration over the previous two weeks
• Hemoglobin >= 10 mg/dL with no blood transfusion in the past 28 days (within 28 days
prior to administration of study drug)
• Platelet count >= 100 x 10^9/L (within 28 days prior to administration of study drug)
• Absolute neutrophil count (ANC) >= 1.5 x 10^9/L (within 28 days prior to
administration of study drug)
• Patients must have creatinine clearance estimated of >= 51 mL/min using the Cockcroft
Gault equation or based on a 24-hour urine test (within 28 days prior to
administration of study drug)
• Serum bilirubin =< 1.5 X upper limit of normal (ULN) (within 28 days prior to
administration of study drug)
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x ULN (within
28 days prior to administration of study drug)
• Urine protein: creatinine (UPC) < 1 or < 2+ proteinuria on two consecutive dipsticks
taken no less than 1 week apart. Patients with 2+ proteinuria on dipstick must also
have UPC < 0.5 on 2 consecutive samples (within 28 days prior to administration of
study drug)
• Patients must be able to swallow and retain oral medications and without
gastrointestinal illnesses that would preclude absorption of cediranib, olaparib, or
AZD5363 (capivasertib)
• Patients must have adequately controlled blood pressure (BP), with a BP no greater
than 140 mmHg (systolic) and 90 mmHg (diastolic) for eligibility; patients must have a
BP of =< 140/90 mmHg taken in the clinic setting by a medical professional within 2
weeks prior to starting study; patients with hypertension may be managed with up to a
maximum of three antihypertensive medications; it is strongly recommended that
patients who are on three antihypertensive medications be followed by a cardiologist
or blood pressure specialist for management of blood pressure while on protocol
• Note: Patients must be willing and able to check and record daily blood pressure
readings
• The patient or a legally authorized representative must provide study-specific
informed consent prior to study entry
• Adequately controlled thyroid function, with no symptoms of thyroid dysfunction
• Postmenopausal or evidence of non-childbearing status for women of childbearing
potential as confirmed by a negative urine or serum pregnancy test within 7 days prior
to start of investigational products (IPs); postmenopausal is defined as:
• Age >= 60 years, or
• Age < 60 with any one or more of the conditions below:
• Amenorrheic for >= 1 year in the absence of chemotherapy and/or hormonal
treatments,
• Luteinizing hormone and/or follicle stimulating hormone and/or estradiol
levels in the post-menopausal range
• Radiation-induced oophorectomy with last menses > 1 year ago,
• Chemotherapy-induced menopause with > 1 year interval since last menses,
• Surgical sterilization (bilateral oophorectomy or hysterectomy)
• Patients must have a life expectancy of greater than 16 weeks
• Patients with a previous diagnosis of immune or inflammatory colitis or chronic
diarrhea > 1 month without immune or inflammatory colitis are eligible with adequately
controlled colitis (no diarrhea greater than grade 1 for at least 28 days) and in the
absence of symptoms related to colonic dysfunction; patients who required steroids for
prior immune related colitis are not eligible
• Females of child-bearing potential should use two forms of highly reliable methods of
contraception from the time of screening until 4 weeks after discontinuing study
treatment.
• Acceptable methods of contraception include:
• Established use of oral, injected or implanted hormonal methods of
contraception.
• Placement of an intrauterine device or intrauterine system.
• Barrier methods of contraception: condom or occlusive cap (diaphragm or
cervical/vault caps) with spermicidal foam/gel/film/cream/suppository.
• Male partner sterilization (with the appropriate post-vasectomy
documentation of the absence of sperm in the ejaculate).
• True abstinence (i.e., not engaging in sexual activity for the total
duration of study treatment and the treatment washout period is an
acceptable practice; however, periodic abstinence, the rhythm method, and
the withdrawal method are not acceptable methods of birth control).
• Bilateral tubal occlusion or salpingectomy
• Acceptable non-hormonal birth control methods include:
• Total/True abstinence: When the patient refrains from any form of sexual
intercourse and this is in line with their usual and/or preferred lifestyle;
this must continue for the total duration of the trial and for at least 1
month after the last dose of study drug <>. [Periodic abstinence (e.g., calendar, ovulation,
symptothermal, post-ovulation methods, or declaration of abstinence solely
for the duration of a trial) and withdrawal are not acceptable methods of
contraception]
• Vasectomised sexual partner PLUS male condom. With participant assurance
that partner received post-vasectomy confirmation of azoospermia.
• Tubal occlusion PLUS male condom
• Intrauterine device (IUD) PLUS male condom. Provided coils are
copper-banded.
• Acceptable hormonal methods:
• Normal and low dose combined oral pills PLUS male condom.
• Cerazette (desogestrel) PLUS male condom. Cerazette is currently the only
highly efficacious progesterone-based pill.
• Hormonal shot or injection (e.g., Depo-Provera) PLUS male condom.
• Etonogestrel implants (e.g., Implanon, Norplant) PLUS male condom.
• Norelgestromin/EE transdermal system PLUS male condom
• Intrauterine system [IUS] device (e.g., levonorgestrel releasing IUS
-Mirena) PLUS male condom.
• Intravaginal device (e.g., EE and etonogestrel) PLUS male condom
Exclusion Criteria:
• Prior enrollment into a clinical trial including cediranib or olaparib; Note: prior
bevacizumab is not an exclusion criterion
• Prior enrollment into a clinical trial including cediranib, olaparib, AZD5363
(capivasertib), durvalumab (MEDI4736), or the combination of lenvatinib and
pembrolizumab. Note: Prior bevacizumab or single-agent immune checkpoint blockade,
excluding durvalumab (MEDI4736), is not an exclusion criterion
• Prior chemotherapy, endocrine therapy, radiotherapy, or investigational agents within
4 weeks
• More than one prior line of treatment with immune checkpoint blockade therapy
• Current signs/symptoms of bowel obstruction and/or signs/symptoms of bowel obstruction
within the preceding 3 months
• History of gastrointestinal perforation; patients with a history of abdominal fistula
will be considered eligible if the fistula was surgically repaired or has healed,
there has been no evidence of fistula for at least 6 months, and patient is deemed to
be at low risk of recurrent fistula
• Uncontrolled intercurrent illness including, but not limited to known ongoing or
active infection, symptomatic congestive heart failure, unstable angina pectoris,
cardiac arrhythmia, extensive interstitial bilateral lung disease on high resolution
computed tomography (HRCT) scan or psychiatric illness/social situations that would
limit compliance with study requirements
• Concomitant use of known strong cytochrome (CYP) 3A inhibitors (e.g., itraconazole,
telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or
cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate
CYP3A inhibitors (e.g. ciprofloxacin, erythromycin, diltiazem, fluconazole,
verapamil); the required washout period prior to starting study treatments is 2 weeks
for strong inhibitors, and at least 1 week for moderate inhibitors
• Concomitant use of potent inhibitors or inducers of CYP3A4 within 2 weeks before the
start of study treatment (3 weeks for St John's wort), or sensitive substrates of
CYP3A4, CYP2C9 and/or CYP2D6 with a narrow therapeutic window within 1 week before the
start of study treatment. Concomitant use of drugs known to prolong the QT interval
within 5 half-lives of the first dose of study treatment
• Pregnant women are excluded from this study because cediranib and olaparib are agents
with the potential for teratogenic or abortifacient effects; because there is an
unknown but potential risk of adverse events in nursing infants secondary to treatment
of the mother with cediranib and olaparib, breastfeeding should be discontinued if the
mother is treated with cediranib or olaparib; these potential risks may also apply to
other agents used in this study; for women of childbearing capacity a negative
pregnancy test is required
• Known human immunodeficiency virus (HIV)-positive individuals are ineligible because
of the potential for pharmacokinetic interactions between many anti-HIV drugs and
cediranib, olaparib, and/or AZD5363 (capivasertib); in addition, these individuals are
at increased risk of lethal infections when treated with marrow-suppressive therapy
• Known active hepatitis B or hepatitis C infection on antiviral treatment
• Prior history of stroke or transient ischemic attack within the last 6 months
• Left ventricular ejection fraction (LVEF) < lower limit of normal (LLN) per
institutional guidelines, or < 55%, if threshold for normal not otherwise specified by
institutional guidelines, for patients with the following risk factors:
• Prior treatment with anthracyclines
• Prior treatment with trastuzumab
• Prior central thoracic radiation therapy (RT), including exposure of heart to
therapeutic doses of ionizing RT
• History of myocardial infarction within 6-12 months prior to start of IPs
• Prior history of other significant impaired cardiac function
• Patients with any of the following:
• History of myocardial infarction within 6 months prior to starting treatment
• Unstable angina
• Resting electrocardiogram (ECG) with clinically significant abnormal findings or
with corrected QT interval (QTc) > 470 msec on 2 or more time points within a 24
hour period or family history of long QT syndrome
• New York Heart Association functional classification of III or IV
• Prior history of hypertensive crisis or hypertensive encephalopathy
• Major surgical procedure within 4 weeks prior to starting treatment; patients must
have recovered from any effects of any major surgery and surgical wound should have
healed prior to starting treatment
• History of intra-abdominal abscess within 3 months prior to starting treatment
• Patients may not use any complementary or alternative medicines including natural
herbal products or folk remedies as they may interfere with the effectiveness of the
study treatments
• No prior allogeneic bone marrow transplant or double umbilical cord blood
transplantation (dUBCT)
• Whole blood transfusions in the last 120 days prior to entry to the study (packed red
blood cells and platelet transfusions are acceptable)
• Patients with myelodysplastic syndrome (MDS)/treatment-related acute myeloid leukemia
(t-AML) or with features suggestive of MDS/AML
• Central nervous system metastases:
• Symptomatic uncontrolled brain metastases requiring corticosteroid treatment;
history of spinal cord compression unless after definitive treatment the patient
has clinically stable disease (SD) for at least 28 days prior to starting IPs; in
the absence of these features and in an asymptomatic patient a scan to confirm
the absence of brain metastases is not required
• Other malignancy within the last 5 years except for:
• Curatively treated basal cell or squamous cell carcinoma of skin; in situ cancer
of the cervix, ductal carcinoma in situ of the breast or stage 1, grade 1
endometrial carcinoma
• Curatively treated other solid tumors including lymphomas (without bone marrow
involvement) with no evidence of disease for >= 5 years prior to start of IPs
• Persisting >= grade 2 Common Terminology Criteria for Adverse Events (CTCAE) toxicity
(except alopecia and grade 2 peripheral neuropathy) from previous anti-cancer
treatment(s)
• History of allergic reactions attributed to compounds of similar chemical or biologic
composition to cediranib, olaparib, AZD5363 (capivasertib), or durvalumab (MEDI4736)
• Pneumonitis or moderate-severe pre-existing pulmonary disease
• Patients who have a diagnosis of immunodeficiency or are receiving systemic steroid
therapy or any other form of immunosuppressive therapy within 7 days of enrollment.
• Premedication with steroids for CT scan contrast is allowed.
• Inhaled or topical corticosteroids are allowed.
• The use of mineralocorticoids (e.g., fludrocortisone) for patients with
orthostatic hypotension or adrenocortical insufficiency is allowed.
• The use of physiologic doses of corticosteroids may be approved after
consultation with the study chair
• Patients with active autoimmune disease or history of autoimmune disease that might
recur, which may affect vital organ function or require immune suppressive treatment
including systemic corticosteroids. This includes, but is not limited to, patients
with a history of immune related neurologic disease, multiple sclerosis, autoimmune
(demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis; systemic
autoimmune disease such as SLE, connective tissue diseases, scleroderma, inflammatory
bowel disease (IBD), Crohn's, ulcerative colitis, hepatitis; and patients with a
history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid
syndrome because of the risk of recurrence or exacerbation of disease
• Patients with vitiligo, endocrine deficiencies including type I diabetes mellitus,
thyroiditis managed with replacement hormones including physiologic corticosteroids
are eligible
• Patients with rheumatoid arthritis and other arthropathies, Sjogren's syndrome and
psoriasis controlled with topical medication and patients with positive serology, such
as antinuclear antibodies (ANA), anti-thyroid antibodies should be evaluated for the
presence of target organ involvement and potential need for systemic treatment but
should otherwise be eligible
• Active infection including tuberculosis (clinical evaluation that includes clinical
history, physical examination and radiographic findings, and tuberculosis [TB] testing
in line with local practice)
Endometrial Undifferentiated Carcinoma, Endometrioid Adenocarcinoma, Stage IVA Uterine Corpus Cancer AJCC v7, Stage IVB Uterine Corpus Cancer AJCC v7, Stage IV Uterine Corpus Cancer AJCC v7, Recurrent Uterine Corpus Cancer, Recurrent Endometrial Serous Adenocarcinoma
A Study of LY3484356 in Participants With Advanced or Metastatic Breast Cancer or Endometrial Cancer (EMBER)
The reason for this study is to see if the study drug LY3484356 alone or in combination with
other anticancer therapies is safe and effective in participants with advanced or metastatic
breast cancer or endometrial cancer.
All study parts:
• Participants must be willing to provide adequate archival tissue sample
• Participants must be willing to use highly effective birth control
• Participants must have adequate organ function
• Participants must be able to swallow capsules
Dose escalation- Participants must have one of the following:
• Parts A and B: ER+ HER2- breast cancer with evidence of locally advanced unresectable
or metastatic disease who have had the following:
• Part A: may have had up to 1 prior regimen of any kind for in the advanced/metastatic
setting and no prior cyclin-dependent kinase 4/6 (CDK4/6) inhibitor therapy.
• Part B: may have had up to 2 prior regimens, no more than 1 of which may be endocrine
therapy in the advanced/metastatic setting, and must have received a prior CDK4/6
inhibitor
• Cohort E4: No prior everolimus.
• Cohort E5: No prior alpelisib and must have a phosphatidylinositol 3-kinase catalytic
α (PIK3Cα) mutation as determined by local testing.
• Part C: ER+, human epidermal growth factor receptor 2 positive (HER2+) breast cancer
with evidence of locally advanced unresectable or metastatic disease who have had at
least 2 HER2-directed therapies in any setting.
• Part D: ER+, EEC that has progressed after platinum containing chemotherapy and no
prior fulvestrant or aromatase inhibitor therapy.
• Part E: ER+ and HER2+ breast cancer with evidence of locally advanced, unresectable,
or metastatic disease.
• Part E: Participants must have received induction taxane chemotherapy combined with
trastuzumab + pertuzumab as first-line treatment for advanced/metastatic disease and
must not have progressed on this regimen.
• Part E: Participants must not have received more than 1 HER2-directed regimen or any
endocrine therapy for advanced disease or any prior CDK4/6 inhibitor therapy.
Participants with ER+/HER2- breast cancer enrolled in this study must have had evidence of
clinical benefit while on endocrine therapy for at least 24 months in the adjuvant setting
or at least 6 months in the advanced/metastatic setting or have untreated de novo
metastatic breast cancer
Exclusion Criteria:
• Participants must not have certain infections such as hepatitis or tuberculosis or HIV
that are not well controlled
• Participants must not have another serious medical condition
• Participants must not have cancer of the central nervous system that is unstable
• Participants must not be pregnant or breastfeeding
A Phase 1 Dose Escalation and Cohort Expansion Study of TSR-042, an Anti-PD-1 Monoclonal Antibody, in Patients With Advanced Solid Tumors (GARNET)
This is a multicenter, open-label, first-in-human Phase 1 study evaluating the
anti-programmed death receptor 1 (anti-PD-1) antibody TSR-042 in patients with advanced solid
tumors who have limited available treatment options. The study will be conducted in 2 parts:
dose escalation and cohort expansion. The cohort expansion may include up to 5 tumor types,
including endometrial and Non-Small Cell Lung cancer.
• Patient is at least 18 years of age
• Patient with advanced or metastatic solid tumor and has disease progression after
treatment with available therapies that are known to confer clinical benefit or who
are intolerant to treatment that meets the following requirements for the part of the
study they will participate in:
1. Part 1: Patient with any advanced or metastatic solid tumor
2. Part 2A: Patient with any advanced or metastatic solid tumor
3. Part 2B: Patient with Non-Small Cell Lung Cancer (NSCLC) and Endometrial cancers
• Female patients, if of childbearing potential, must have a negative serum pregnancy
test within 72 hours prior to the date of the first dose of study medication.
• Female patients of childbearing potential must agree to use 2 adequate methods of
contraception with their partner starting with the screening visit through 150 days
after the last dose of study therapy.
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2 for Part 1 and ≤ 1
for Part 2. Adequate organ function.
Exclusion Criteria:
• Patient has received prior therapy with an anti- programmed death receptor 1
(anti-PD-1), anti-PD-1- ligand-1 (anti-PD-L1), or anti-PD-1 ligand-2 (anti-PD- L2)
agent.
• Known uncontrolled central nervous system (CNS) metastases and/or carcinomatous
meningitis. Note: Patients with previously treated brain metastases may participate
provided they are stable (without evidence of progression by imaging for at least 4
weeks prior to the first dose of study treatment and any neurologic symptoms have
returned to baseline), have no evidence of new or enlarging brain metastases, and are
clinically stable off steroids for at least 7 days prior to study treatment.
Carcinomatous meningitis precludes a patient from study participation regardless of
clinical stability.
• Known additional malignancy that progressed or required active treatment within the
last 2 years. Exceptions include basal cell carcinoma of the skin, squamous cell
cancer (SqCC) of the skin that has undergone potentially curative therapy, or in situ
cervical cancer.
• Known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies).
• Known active hepatitis B (eg, hepatitis B surface antigen [HBsAg] reactive) or
hepatitis C (eg, hepatitis C virus ribonucleic acid (HCV RNA) (qualitative) is
detected).
• Active autoimmune disease that has required systemic treatment in the past 2 years
(ie, with use of disease- modifying agents, corticosteroids, or immunosuppressive
drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid
replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
form of systemic treatment.
• History of interstitial lung disease.
• Histological confirmed primary SCC of the vulva
• T1 tumor, not encroaching urethra/vagina/anus
• Depth of invasion > 1mm
• Tumor diameter < 4cm
• Unifocal tumor
• No enlarged (>1.5cm) or suspicious inguinofemoral lymph nodes at imaging
(CT/MRI/ultrasound)
• Possibility to obtain informed consent
• Metastatic sentinel lymph node; size of metastasis > 2mm and / or extracapsular
extension, or
• Metastatic sentinel lymph node: more than 1 SN with metastasis ≤ 2mm
• Patients are able to understand requirements of study, provide written informed
consent and comply with the study and follow-up procedures
• Adequate bone marrow, renal and liver function:
• Absolute neutrophil count ≥ 1.5 x 109 /L
• Platelet count ≥ 100 x 109 /L
• Creatinine clearance ≥ 40 ml/min measured by the Cockroft Gault formula
• Total bilirubin < 1.25 x ULN Aspartate transaminase (AST) and alanine
transaminase (ALT) ≤ 2.5 x ULN
• Performance status of 0, 1 or 2 on the Eastern Cooperative Oncology Group (ECOG) Scale
(Appendix A)
• Age 18 years or older
• Life expectancy of ≥ 12 weeks
• Written informed consent
Exclusion Criteria:
• Inoperable tumors and tumors > 4cm
• Multifocal tumors
• Tumors with other pathology than squamous cell carcinoma
• Patients with enlarged / suspicious lymph nodes which are proven metastatic after fine
needle aspiration cytology
• No other carcinomas, other than basal cell carcinomas, within last 5 years
• History of pelvic radiotherapy
• History of any infection requiring hospitalization or antibiotics within 2 weeks
before enrollment
• Pregnant female or nursing mother
• Desire to become pregnant
• Known brain or spinal cord metastases unless adequately treated (surgery or
radiotherapy) with no evidence of progression and neurologically stable off
anticonvulsants and steroids
• Unstable angina, myocardial infarction, cerebrovascular accident, > Class II
congestive heart failure according to the New York Heart Association Classification
for Congestive Heart Failure (see Appendix B) within 6 months before enrollment
Radiation: Radiotherapy combined with cisplatin, Drug: Cisplatin
Phase 1/2a Evaluation of Adding AL3818 to Standard Platinum-Based Chemotherapy in Subjects With Recurrent or Metastatic Endometrial, Ovarian, Fallopian, Primary Peritoneal or Cervical Carcinoma (AL3818-US-002) (AL3818)
This trial is a Phase 1b/2a trial designed to evaluate the safety and efficacy of adding oral
AL3818 to standard platinum-based chemotherapy concurrently and continued as a maintenance
therapy for up to 12 months.
• Female ≥ 18 years
• Previously histologically proven diagnosis of
a. Endometrial Cancer: recurrent or persistent endometrial carcinoma refractory to
conventional therapy or established treatments with the following histologic
epithelial cell types i. Endometrioid adenocarcinoma, serous adenocarcinoma,
undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma,
adenocarcinoma not otherwise specified, mucinous adenocarcinoma, squamous cell
carcinoma, and transitional cell carcinoma b. Ovarian Cancer: recurrent or persistent
ovarian or primary peritoneal cancer refractory to established treatments with the
following histologic epithelial cell types i. Endometrioid adenocarcinoma, serous
adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed
epithelial carcinoma, adenocarcinoma not otherwise specified.
c. Cervical cancer: squamous cell carcinoma of the cervix refractory to conventional
therapy or established treatments with the following histologic epithelial cell types:
i. Squamous cell carcinoma, adenosquamous carcinoma or adenocarcinoma Measurable
disease defined as at least one lesion that can be accurately measured in at least one
dimension (longest dimension to be recorded). Each lesion must be ≥ 20mm when measured
by conventional techniques, including palpation, plain x-ray, CT, and MRI or ≥ 10mm
when measured by spiral CT.
• Life expectancy ≥ 3 months
• Able to take orally administered study medication
• Must sign approved informed consent and authorization permitting release of personal
health information.
• Patient must have adequate:
1. Bone marrow function: absolute neutrophil count (ANC) ≥ 1,500/mm^3, equivalent to
Common Toxicity Criteria (CTC) grade 1, platelets ≥ 100,000/mm^3
2. Renal function: creatinine ≤ 1.5 x institutional upper limit normal (ULN), CTC
grade 1. Note: If creatinine is > 1.5 x ULN, creatinine clearance must be > 50
mL/min.
3. Hepatic function: bilirubin ≤ 1.5 x ULN (CTC grade 1) or ≤ 3.0 x ULN for subjects
with Gilbert Syndrome; AST and ALT ≤ 3.0 ×ULN.
4. Coagulation profile: PT such that international normalized ratio (INR) is ≤ 1.55
(or an in-range INR, usually between 2 and 3, if a patient is on a stable dose of
therapeutic warfarin or low molecular weight heparin) and a PTT < 1.2 times
control.
5. ECOG performance ≤ 2
• Patient of child-bearing potential must agree to use contraceptive measures starting 1
week before the administration of the first dose of AL3818 until 4 weeks after
discontinuing study drug and have a negative serum pregnancy test prior to study entry
and cannot be lactating.
• Ability and willingness to comply with the study protocol for the duration of the
study and with follow-up procedures.
Exclusion Criteria:
• Patients with serious, non-healing wound, ulcer or bone fracture.
• Patients with active bleeding or pathologic conditions that carry high risk of
bleeding, such as known bleeding disorder, coagulopathy, or tumor involving major
vessels.
• Patient with history or evidence upon physical examination of CNS disease, including
primary brain tumor, seizures not controlled with standard medical therapy, any brain
metastases or history of cerebrovascular accident (CVA, stroke) transient ischemic
attack (TIA) or subarachnoid hemorrhage within 6 months of the first date of treatment
on this study.
a. Patients with metastatic CNS tumors may participate in this trial, if the patient
is > 4 weeks from therapy completion (including radiation and/or surgery), is
clinically stable at the time of study entry and is not receiving corticosteroid
therapy.
• Patients with proteinuria: patients discovered to have a urine protein of 1+ on
dipstick or ≥ 30 mg/dl at baseline should undergo a 24-hour urine collection, which
must be an adequate collection and must demonstrate < 1000 mg protein/24 hours to
allow participation in the study.
• Patients with clinically significant cardiovascular disease including uncontrolled
hypertension, myocardial infarction or unstable angina within 6 months prior to
registration. New York Heart Association (NYHA) Grade II or greater congestive heart
failure, Serious cardiac arrhythmia requiring medication, Grade II or greater
peripheral vascular disease.
• Patients who are pregnant or nursing.
• Women of childbearing potential who are unable to use contraceptive measures during
study therapy and for at least 3 months after completion of AL3818 therapy.
• Patients with uncontrolled hypokalemia, hypomagnesaemia, and/or hypocalcaemia.
• Hemoptysis within 3 months prior to first scheduled dose of AL3818.
• Patients with acute or chronic liver disease, active hepatitis A or B with known
cirrhosis or liver dysfunction.
• Cytotoxic chemotherapy, immunotherapy, or radiotherapy within 4 weeks (6 weeks in
cases of mitomycin C, nitrosourea, lomustine) prior to first scheduled dose of AL3818
or a major surgical procedure within 28 days or minor surgical procedure performed
within 7 days prior to first scheduled dose of AL3818.
• Concomitant treatment with strong inhibitors or inducers of CYP3A4, CYP2C9 and CYP2C19
who cannot be switched to other alternative medications .
• Known history of human immunodeficiency virus infection (HIV).
• Subjects with active bacterial infections (other than uncomplicated urinary tract
infection) and/or receiving systemic antibiotics.
• Patients with other invasive malignancies, with the exception of non-melanoma skin
cancer, who had (or have) any evidence of other cancer present within the last 5 years
or whose previous cancer treatment contraindicates this protocol therapy.
• History of non-malignant GI bleeding, gastric stress ulcerations, or peptic ulcer
disease within the past 3-months that in the opinion of the investigator may place the
patient at risk of side effects on an anti-angiogenesis product.
• History of significant vascular disease (e.g. aortic aneurysm, aortic dissection).
• Intra-abdominal abscess within the last 3 months.
• Pre-existing uncontrolled hypertension as documented by 2 baseline BP readings taken
at least one hour apart, defined as systolic bloodpressure (BP) >160 mm Hg or
diastolic BP > 90 mm Hg pressure.
• QTcF>470 msec on screening ECG.
• A history of additional risk factors for TdP (e.g., heart failure, hypokalemia, family
history of Long QT Syndrome).
• The use of concomitant medications that prolong the QT/QTc interval. Baseline
echocardiogram (within 2 months) with left ventricular ejection fraction (LVEF) < 50%.
• History of difficulty swallowing, malabsorption, active partial or complete bowel
obstruction, or other chronic gastrointestinal disease or condition that may hamper
compliance and/or absorption of AL3818.
• History of pancreatitis and/or renal disease or pancreatitis that includes
histologically confirmed glomerulonephritis, biopsy proven tubulointerstitial
nephritis, crystal nephropathy, or other renal insufficiencies.
• Treatment with an investigational agent within the longest time frame of either 5
half- lives or 30 days of initiating study drug.
• Known recreational substance abuse.
• Known hypersensitivity to AL3818 or components of the formulation.
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
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
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
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
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)
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