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.
Effect of Tumor Treating Fields (TTFields, 200 kHz) Concomitant With Weekly Paclitaxel for the Treatment of Recurrent Ovarian Cancer (ENGOT-ov50 / GOG-3029 / INNOVATE-3)
The study is a prospective, randomized controlled phase III trial aimed to test the efficacy
and safety of Tumor Treating Fields (TTFields) concomitant with weekly paclitaxel for the
treatment of recurrent ovarian cancer . The device is an experimental, portable, battery
operated device for chronic administration of alternating electric fields (termed TTFields or
TTF) to the region of the malignant tumor, by means of surface, insulated electrode arrays.
1. 18 years of age and older
2. Epithelial histology of ovarian/primary peritoneal or fallopian tube carcinoma at the
time of diagnosis
3. Life expectancy of ≥ 12 weeks
4. Maximum two prior lines of systemic therapy following diagnosis of platinum-resistance
5. Maximum total of 5 prior lines of systemic therapy
6. Amenable to receive weekly paclitaxel and able to operate the NovoTTF-100L(O) System
7. ECOG 0-1
8. Evaluable (measurable or non-measurable) disease in the abdominal/pelvic region per
RECIST V1.
9. Signed informed consent form for the study protocol
Exclusion Criteria:
1. Primary platinum-refractory disease (progression per RECIST V1.1 during or within 1
month after first line therapy), while secondary platinum-refractory disease is
allowed
2. Prior disease progression on a weekly paclitaxel for recurrent disease
3. Brain metastasis or leptomeningeal spread of the tumor
4. Albumin level <25 gram/liter (subjects should not receive total parenteral nutrition
or albumin within 2 weeks of the test)
5. CTCAE V5.0 Grade 3 or higher peripheral neuropathy
6. Implantable electrical medical devices
7. Known allergies to medical adhesives or hydrogel
8. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to paclitaxel or
drugs similar or related to paclitaxel, except for cases that were able to undergo
desensitization per investigator
9. Prior malignancies treated primarily or for recurrence within 2 years prior to
inclusion in this study, except for completely resected non-melanomatous skin
carcinoma, or successfully treated in situ carcinoma of the skin, breast or cervix of
the uterus
10. Serious co-morbidities
11. Concurrent anti-tumor therapy beyond weekly paclitaxel, excluding hormonal therapy for
breast cancer
12. Concurrent active treatment in another clinical trial. However prior participation in
clinical trials is allowed as well as participation during survival follow-up
13. Pregnancy or breast-feeding (female patients with reproductive potential and their
partners must accept to use effective contraception throughout the entire study period
and for 3 months after the end of treatment). All patients who are capable of becoming
pregnant must take a pregnancy test which is negative within 72 hours before beginning
treatment. The definition of effective contraception is left up to the decision of the
investigator
14. Admitted to an institution by administrative or court order
A Study to Compare Two Surgical Procedures in Women With BRCA1 Mutations to Assess Reduced Risk of Ovarian Cancer (SOROCk)
This trial studies how well two surgical procedures (bilateral salpingectomy and bilateral
salpingo-oophorectomy) work in reducing the risk of ovarian cancer for women with BRCA1
mutations. Bilateral salpingectomy involves the surgical removal of fallopian tubes, and
bilateral salpingo-oophorectomy involves the surgical removal of both the fallopian tubes and
ovaries. This study may help doctors determine if the two surgical procedures are nearly the
same for ovarian cancer risk reduction for women with BRCA1 mutations.
• Patients who have declined or elected to defer risk-reducing salpingo-oophorectomy
(RRSO) after proper counselling to clearly explain the standard of care for BRCA1
mutation carriers (for the BLS with delayed oophorectomy arms) or patients who are
undergoing RRSO (for the RRSO arm)
• At least one intact ovary and fallopian tube
• Positive Clinical Laboratory Improvement Act (CLIA)-approved test results for
pathogenic or likely pathogenic germline BRCA1 mutation in the patient herself.
Documentation of the result is required
• Premenopausal; defined as < 12 months of amenorrhea. However, for those patients with
>= 12 months of amenorrhea who may be pre-menopausal or patients with a prior
hysterectomy with at least one retained ovary/tube, levels of follicle stimulating
hormone (FSH), luteinizing hormone (LH), and in the premenopausal range per local
institutional standards will be acceptable
• Concurrently planned or prior hysterectomy is permitted as long as at least one
fallopian tube and one ovary had been retained
• Transvaginal ultrasound (TVUS) and CA-125 within 180 days of registration
• The patient or a legally authorized representative must provide study-specific
informed consent prior to study entry
• Patient must have negative urine pregnancy test within 14 days prior to registration
based on local institutional policies
Exclusion Criteria:
• Women with a history of any prior cancer who have received chemotherapy within the
past 12 months, hormonal therapy in the past 90 days, or radiotherapy to abdomen or
pelvis at any prior time
• Prior history of ovarian cancer, including low malignant potential neoplasms (LMP),
primary peritoneal carcinoma, or fallopian tube carcinoma
• Patients medically unfit for the planned surgical procedure
• Patients with abnormal screening tests (TVUS, CA-125) suspicious for occult or gross
pelvic malignancy or neoplasm within the past 180 days
• An abnormal TVUS is defined as morphologic or structural variations suspicious
for ovarian malignancy or complex cystic lesions (simple cysts < 5 cm in maximal
diameter are not exclusionary)
• An abnormal CA-125 is defined as a level > 50 U/ml in this study population of
premenopausal women if they are not current users of oral contraceptives; an
abnormal CA-125 is defined as a level > 40 U/ml for premenopausal women who are
current users of oral contraceptives
• Women who are currently pregnant or plan to become pregnant in the future
PARP Inhibition During Pre-surgical Window in Breast/Ovary Cancer
Study involves surgery for cytoreduction or laparoscopy to determine if you are a candidate
for tumor debulking or a tissue biopsy. Following this surgery you will receive chemotherapy.
This study will administer 7 days of treatment with a targeted therapy called Lynparza.
Lynparza and/or other PARP inhibitors have been FDA approved for the treatment of ovarian and
breast cancer. Tissue biopsy will be done before a 7 day course of Lynparza in order to
correlate molecular changes to response to treatment. Participation in this trial will
require an additional tumor biopsy which will occur either before or after treatment of
Lynparza.
• All patients must have cytology/ biopsy proven diagnosis of a mullerian carcinoma,
high clinical index of suspicion for ovarian cancer OR triple negative, BRCA mutated
breast cancer.
• Patients may not have received prior treatment for breast or ovarian cancer.
• All patients must be of at least 18 years of age.
• ECOG Performance status must be 0,1 or 2.
• Patients must not have received a prior PARP inhibitor
• Adequate organ and marrow function as defined below:
• absolute neutrophil count >/= 1500/mcL
• Platelets > /= 100,000 /mcl
• Hemoglobin >/= 8 g/dl
• Total bilirubin = 1.5 x the institutional ULN
• AST, ALT = 3 x the institutional ULN
• Creatinine = the institutional ULN
• Women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control; abstinence) prior to study entry, for
the duration of study participation, and for 90 days following completion of therapy.
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,
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).
• Patients must be able to swallow and retain oral medications.
• Ability to understand and the willingness to sign a written informed consent.
Exclusion Criteria:
• Chemotherapy, radiotherapy, or other cancer therapy within 4 weeks prior to starting
study treatment. Subjects must have recovered from prior treatment-related to
toxicities to grade 1 or baseline (excluding alopecia and clinically stable toxicities
requiring ongoing medical management, such as hypothyroidism from prior immune
checkpoint inhibitor treatment).
• Subjects may not be receiving any other investigational agents for the treatment of
the cancer under study.
• Brain metastases
• History of allergic reactions attributed to compounds of similar chemical or biologic
composition to Lynparza or other agents used in study.
• 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.
• Subjects must not be pregnant or nursing due to the potential for congenital
abnormalities and the potential of this regimen to harm nursing infants.
Drug: Lynparza
Breast Cancer, Ovarian Cancer, Breast - Female, Ovary
Use of the CA 125 Algorithm for the Early Detection of Ovarian Cancer in Low Risk Women
The goal of this clinical research study is to evaluate a method involving a blood test,
called CA-125, that may be helpful in the early detection of ovarian cancer in women who are
at low risk.
1. Female, >/= 50 years old or less than 75 years old.
2. Postmenopausal (>/= 12 months amenorrhea).
3. Have at least one ovary.
4. Cancer-free and have not received any chemotherapy or radiation therapy for >/=12
months prior to enrolling on this study.
5. Willingness to return for CA 125 blood tests annually or earlier if indicated.
6. Willingness to return to undergo transvaginal ultrasound if indicated.
7. Women need to provide the name of a gynecologist or qualified healthcare professional
willing to provide appropriate follow-up care if indicated
Exclusion Criteria:
1. Female: Less than 50 years old or older than 75 years at the time of enrollment.
2. Psychiatric or psychological or other conditions which prevent a fully informed
consent.
3. Prior removal of both ovaries.
4. Active non-ovarian malignancy.
5. Women who have a history of non-ovarian malignancy will be eligible if they have no
persistent or recurrent disease and have not received treatment for >12 months. If
they are on SERMS (i.e. tamoxifen or aromatase inhibitors) they will not be excluded.
Women maybe undergoing or have had treatment <12 months prior to study entry for basal
cell carcinoma only.
6. High risk for ovarian cancer due to familial predisposition as defined by the
following: a. Known mutation in BRCA1 of BRCA2. b. Two 1st or 2nd degree relatives of
same lineage who have: two ovarian cancers; one ovarian cancer & one pre-menopausal
breast cancer; two pre-menopausal breast cancers; one pre-menopausal & one
post-menopausal breast cancer. (These conditions can also be met using the patient and
one 1st or 2nd degree female relative.) c. Ashkenazi Jewish descent with one 1st
degree or two 2nd degree relatives with pre-menopausal breast or ovarian cancer or
participant has had pre-menopausal breast cancer. d. 1st or 2nd degree male relative
with breast cancer diagnosed at any age. (First degree relative defined as children,
siblings and parents. Second degree relative defined as half-siblings, aunts, uncles,
nieces, nephews, grandparents, and grandchildren.)
7. Hereditary Nonpolyposis Colorectal Cancer (HNPCC)/Lynch Syndrome: known genetic
mutation, presumed HNPCC carrier, Amsterdam criteria.
Behavioral: Questionnaire
Ovarian Cancer, Ovary
Ovarian Cancer, CA 125 Algorithm, Cancer Detection, Questionnaire, Survey
Study of Chemotherapy With Pembrolizumab (MK-3475) Followed by Maintenance With Olaparib (MK-7339) for the First-Line Treatment of Women With BRCA Non-mutated Advanced Epithelial Ovarian Cancer (EOC) (MK-7339-001/KEYLYNK-001/ENGOT-ov43/GOG-3036)
The purpose of this study is to assess the efficacy and safety of treatment with
carboplatin/paclitaxel* PLUS pembrolizumab (MK-3475) and maintenance olaparib (MK-7339) in
women with epithelial ovarian cancer (EOC), fallopian tube cancer, or primary peritoneal
cancer.
The primary study hypotheses are that the combination of pembrolizumab plus
carboplatin/paclitaxel* followed by continued pembrolizumab and maintenance olaparib is
superior to carboplatin/paclitaxel alone with respect to Progression Free Survival (PFS) per
Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in participants with
programmed death-ligand 1 (PD-L1)-positive tumors (Combined Positive Score [CPS]≥10) and in
all participants, and that the combination of pembrolizumab plus carboplatin/paclitaxel
followed by continued pembrolizumab is superior to carboplatin/paclitaxel alone with respect
to PFS per RECIST 1.1 in participants with PD-L1-positive tumors (CPS≥10) and in all
participants.
• Has histologically confirmed International Federation of Gynecology and Obstetrics
(FIGO) Stage III or Stage IV EOC (high-grade predominantly serous, endometrioid (any
grade), carcinosarcoma, mixed mullerian with high-grade serous component, clear cell,
or low-grade serous OC), primary peritoneal cancer, or fallopian tube cancer
• Has just completed primary debulking surgery or is eligible for primary debulking
surgery or is a potential candidate for interval debulking surgery
• Is a candidate for carboplatin and paclitaxel chemotherapy, to be administered in the
adjuvant or neoadjuvant setting
• Candidates for neoadjuvant chemotherapy, has a cancer antigen 125 (CA-125)
(kilounits/L):carcinoembryonic antigen (CEA; ng/mL) ratio greater than or equal to 25
• Is able to provide a newly obtained core or excisional biopsy of a tumor lesion for
prospective testing of BRCA1/2 and Programmed Cell Death-Ligand 1 (PD-L1) tumor
markers status prior to randomization
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, as
assessed within 7 days prior to initiating chemotherapy in the lead-in period and
within 3 days prior to Day 1 of Cycle 1
• Female participants are not pregnant, not breastfeeding, and at least 1 of the
following conditions applies: a.) Not a woman of childbearing potential (WOCBP) OR b.)
Is a WOCBP and using a contraceptive method that is highly effective, with low user
dependency, or be abstinent from heterosexual intercourse as their preferred and usual
lifestyle, during the Treatment Period and for at least 120 days following the last
dose of pembrolizumab (or pembrolizumab placebo) and bevacizumab (if administered), at
least 180 days following the last dose of olaparib (or olaparib placebo), and at least
210 days following the last dose of chemotherapy and agrees not to donate eggs (ova,
oocytes) to others or freeze/store for her own use for the purpose of reproduction
during this period. The investigator should evaluate the potential for contraceptive
method failure in relationship to the first dose of study treatment. A WOCBP must have
a negative highly sensitive pregnancy test within either 24 hours (urine) or 72 hours
(serum) before the first dose of study treatment. If a urine test cannot be confirmed
as negative, a serum pregnancy test is required. The investigator is responsible for
review of medical history, menstrual history, and recent sexual activity to decrease
the risk for inclusion of a woman with an early undetected pregnancy. Contraceptive
use by women should be consistent with local regulations regarding the methods of
contraception for those participating in clinical studies
• Has adequate organ function
Exclusion Criteria:
• Has mucinous, germ cell, or borderline tumor of the ovary
• Has a known or suspected deleterious mutation (germline or somatic) in either BRCA1 or
BRCA2
• Has a history of non-infectious pneumonitis that required treatment with steroids or
currently has pneumonitis
• Has either myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or has features
suggestive of MDS/AML
• Has a known additional malignancy that is progressing or has required active treatment
in the last 3 years Note: Participants with basal cell carcinoma of the skin, squamous
cell carcinoma of the skin, or carcinoma in situ (e.g. ductal carcinoma in situ,
cervical carcinoma in situ) that has undergone potentially curative therapy are not
excluded.
• Has ongoing Grade 3 or Grade 4 toxicity, excluding alopecia, following chemotherapy
administered during the lead-in period
• Has known active central nervous system metastases and/or carcinomatous meningitis.
Participants with brain metastases may participate provided they were previously
treated (except with chemotherapy) and are radiologically stable, clinically stable,
and no steroids were used for the management of symptoms related to brain metastases
within 14 days prior to randomization. Stable brain metastases should be established
prior to the first dose of study medication lead-in chemotherapy
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
(dosing >10 mg daily of prednisone equivalent) or any other form of immunosuppressive
therapy within 7 days prior to randomization
• Has an active autoimmune disease that has required systemic treatment in the past 2
years (i.e., with use of disease modifying agents, corticosteroids or
immunosuppressive drugs) Note: Replacement therapy (e.g. thyroxine, insulin, or
physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency)
is not considered a form of systemic treatment and is allowed.
• Has a known history of active tuberculosis (TB; Bacillus Tuberculosis)
• Has an active infection requiring systemic therapy
• Has received colony-stimulating factors (eg, granulocyte colony stimulating factor
[G-CSF], granulocyte macrophage colony-stimulating factor [GM-CSF] or recombinant
erythropoietin) within 4 weeks prior to receiving chemotherapy during the lead-in
period
• Is considered to be of poor medical risk due to a serious, uncontrolled medical
disorder, non-malignant systemic disease or active, uncontrolled infection
• Has had surgery to treat borderline tumors, early stage EOC, or early stage fallopian
tube cancer <6 months prior to screening
• Has a known history of human immunodeficiency virus (HIV) infection
• Has a known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg]
reactive) or known active hepatitis C virus (defined as HCV RNA [qualitative] is
detected) infection. Testing for hepatitis B or hepatitis C is required at screening
only if mandated by local health authority. Note: Participants with a history of
hepatitis B but who are HBsAg negative are eligible for the study
• Is either unable to swallow orally administered medication or has a gastrointestinal
(GI) disorder affecting absorption (e.g. gastrectomy, partial bowel obstruction,
malabsorption)
• Has uncontrolled hypertension
• Has current, clinically relevant bowel obstruction (including sub-occlusive disease),
abdominal fistula or GI perforation, related to underlying EOC (for participants
receiving bevacizumab)
• Has a history of hemorrhage, hemoptysis or active GI bleeding within 6 months prior to
randomization (for participants receiving bevacizumab)
• Is a WOCBP who has a positive urine pregnancy test within 72 hours before the first
dose of chemotherapy in the lead-in period and within 72 hours prior to Day 1 of Cycle
1, is pregnant or breastfeeding, or is expecting to conceive children within the
projected duration of the study, starting with screening through 120 days following
the last dose of pembrolizumab (or pembrolizumab placebo) and bevacizumab (if
administered), at least 180 days following the last dose of olaparib (or olaparib
placebo), and at least 210 days following the last dose of chemotherapy
• Has received prior treatment for any stage of OC, including radiation or systemic
anti-cancer therapy (e.g. chemotherapy, hormonal therapy, immunotherapy,
investigational therapy)
• Has received prior therapy with an anti-Programmed Cell Death-1 (anti-PD-1),
anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or
co-inhibitory T-cell receptor (e.g. cytotoxic T lymphocyte antigen-4 [CTLA-4], OX 40,
CD137)
• Has received prior therapy with either olaparib or any other poly(adenosine-ribose)
polymerase (PARP) inhibitor
• Has intraperitoneal chemotherapy planned or has been administered as first-line
therapy
• Has received a live vaccine within 30 days prior to the first dose of study treatment
on Day 1 of Cycle 1
• Has severe hypersensitivity (≥Grade 3) to pembrolizumab, olaparib, carboplatin,
paclitaxel or bevacizumab (if using) and/or any of their excipients
• Is currently receiving either strong (e.g. itraconazole, telithromycin,
clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir,
saquinavir, nelfinavir, boceprevir, telaprevir) or moderate (eg, ciprofloxacin,
erythromycin, diltiazem, fluconazole, verapamil) inhibitors of cytochrome P450
(CYP)3A4 that cannot be discontinued for the duration of the study
• Is currently receiving either strong (e.g. phenobarbital, phenytoin, rifampicin,
rifabutin, rifapentine, carbamazepine, nevirapine, and St John's Wort) or moderate
(e.g. bosentan, efavirenz, modafinil) inducers of CYP3A4 that cannot be discontinued
for the duration of the study
• Has received whole blood transfusions in the last 120 days prior to randomization
• Is currently participating or has participated in a study of an investigational agent
or has used an investigational device within 4 weeks (28 days) of starting
chemotherapy in the Lead-in Period
• Has resting electrocardiogram (ECG) indicating uncontrolled, potentially reversible
cardiac conditions or participant has congenital long QT syndrome
• Has had an allogenic tissue/solid organ transplant, has received previous allogenic
bone-marrow transplant, or has received double umbilical cord transplantation
• Either has had major surgery within 3 weeks of randomization or has not recovered from
any effects of any major surgery
Biological: Pembrolizumab, Drug: Placebo for pembrolizumab, Drug: Carboplatin, Drug: Paclitaxel, Drug: Olaparib, Drug: Placebo for olaparib, Biological: Bevacizumab, Drug: Docetaxel
The main purpose of this study is to monitor the safety and tolerability of avelumab in
participants with solid tumors who continue treatment with avelumab under the same treatment
regimen as in the parent avelumab study.
• Participants under enrollment and treatment in an avelumab clinical study under the
sponsorship of EMD Serono Research & Development Institute, Inc. / Merck KGaA,
Darmstadt, Germany
• Merck Serono Co., Ltd (Japan)
• Participants currently enrolled in an avelumab parent study and are on active
treatment with avelumab or in long-term survival follow-up after treatment
• Participants on active treatment must agree to continue to use highly effective
contraception (that is, methods with a failure rate of less than 1% per year) for both
male and female participants if the risk of conception exists
• Other protocol defined inclusion criteria could apply.
Exclusion Criteria:
• Participants who are pregnant or breastfeeding
• Participants still on active treatment: Known hypersensitivity to any of the study
intervention ingredients
• Participant has been enrolled in the comparator arm of avelumab parent study
• Participant has been withdrawn from avelumab parent study for any reason
• Any other reason that, in the opinion of the Investigator, precludes the participant
from participating in the study
• Other protocol defined exclusion criteria could apply.
Drug: Avelumab
Solid Tumors, Stomach
Avelumab, Non-small cell lung cancer (NSCLC), Renal cell carcinoma (RCC), Urothelial carcinoma (UC), Ovarian cancer
Study of Cabozantinib in Combination With Atezolizumab to Subjects With Locally Advanced or Metastatic Solid Tumors
This is a multicenter Phase 1b, open-label study to assess safety, tolerability, preliminary
efficacy, and pharmacokinetics (PK) of cabozantinib taken in combination with atezolizumab in
subjects with multiple tumor types, including advanced urothelial carcinoma (UC) (including
bladder, renal pelvis, ureter, urethra), renal cell carcinoma (RCC), castration-resistant
prostate cancer (CRPC), non-small-cell lung cancer (NSCLC), triple negative breast cancer
(TNBC), ovarian cancer (OC), endometrial cancer (EC), hepatocellular cancer (HCC), gastric
cancer and gastroesophageal junction cancer (GC/GEJC), colorectal cancer (CRC), head and neck
(H&N) cancer, and differentiated thyroid cancer (DTC). The study consists of two stages: in
the Dose Escalation Stage, an appropriate recommended cabozantinib dose for the combination
with standard dosing regimen of atezolizumab will be established; in the Expansion Stage,
tumor-specific cohorts will be enrolled in order to further evaluate the safety and efficacy
of the combination treatment in these tumor indications. Two exploratory single-agent
cabozantinib (SAC) cohorts will also be enrolled with UC or NSCLC subjects.
1. Cytologically or histologically and radiologically confirmed solid tumor that is
inoperable, locally advanced, metastatic, or recurrent:
• Dose-Escalation Stage:
• Subjects with UC (including renal pelvis, ureter, bladder, urethra) after
prior platinum-based therapy, or
• Subjects with RCC (clear cell, non-clear cell histology) with or without
prior systemic anticancer therapy
• Expansion Stage:
• Inoperable locally advanced or metastatic solid tumor (UC, RCC, CRPC, NSCLC,
TNBC, OC, EC, HCC, GC/GEJC, CRC, H&N cancer, and DTC as outlined above)
2. Measurable disease per RECIST 1.1 as determined by the investigator.
3. Tumor tissue material available (archival or recent tumor biopsy)
4. Recovery to baseline or ≤ Grade 1 CTCAE v4 from toxicities related to any prior
treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive
therapy.
5. Age eighteen years or older on the day of consent.
6. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
7. Adequate organ and marrow function.
8. Sexually active fertile subjects and their partners must agree to use medically
accepted methods of contraception.
9. Female subjects of childbearing potential must not be pregnant at screening.
Exclusion Criteria:
1. Prior treatment with cabozantinib or immune checkpoint inhibitors including
anti-CTLA-4, anti-PD-1, anti-PD-L1, or anti-PD-L2 therapy except in Expansion Cohorts
5, 7,19 and 20. Other restrictions regarding prior therapy may apply.
2. Known brain metastases or cranial epidural disease unless adequately treated and
stable for at least 4 weeks before first dose of study treatment.
3. Concomitant anticoagulation with oral anticoagulants.
4. Subject is receiving systemic steroid therapy or any other form of immunosuppressive
therapy within 2 weeks prior to first dose of study treatment.
5. Administration of a live, attenuated vaccine within 30 days before first dose of study
treatment.
6. The subject has uncontrolled, significant intercurrent or recent illness, including,
but not limited to, an active or history of autoimmune disease or immune deficiency;
idiopathic pulmonary fibrosis, organizing pneumonia, pneumonitis; active infection
requiring systemic treatment, infection with human immunodeficiency virus (HIV),
AIDS-related illness, acute or chronic hepatitis B or C infection, positive test for
tuberculosis, moderate to severe hepatic impairment (Child-Pugh B or C).
7. Pregnant or lactating females.
8. Previously identified allergy or hypersensitivity to components of the study treatment
formulations.
9. Diagnosis of another malignancy within 2 years before first dose of study treatment.
Active Surveillance, Bleomycin, Carboplatin, Etoposide, or Cisplatin in Treating Pediatric and Adult Patients With Germ Cell Tumors
This phase III trial studies how well active surveillance, bleomycin, carboplatin, etoposide,
or cisplatin work in treating pediatric and adult patients with germ cell tumors. Active
surveillance may help doctors to monitor subjects with low risk germ cell tumors after their
tumor is removed. Drugs used in chemotherapy, such as bleomycin, carboplatin, etoposide, and
cisplatin, 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.
• There is no age limit for the low risk stratum (stage I ovarian immature teratoma and
stage I non-seminoma or seminoma malignant GCT [all sites])
• Standard risk 1: Patient must be < 11 years of age at enrollment
• Standard risk 2: Patients must be >= 11 and < 25 years of age at enrollment
• Patients enrolling on one of the low risk arms must be newly diagnosed with a stage I
germ cell tumor; for the standard risk arms, patients must be newly diagnosed with
metastatic germ cell tumor (stage II or higher); histologic confirmation of a primary
extracranial germ cell tumor in any of the categories outlined below is required of
all patients at enrollment except for those who were initially diagnosed with stage I
non-seminoma malignant GCT and later recur during observation post surgery off study;
for these patients, if elevated tumor markers rise to > 5 x upper limit of normal
(ULN) on at least 2 measurements taken at least 1 week apart, a diagnostic biopsy is
not required for enrollment
• Low risk stage I immature teratoma (IT); site: ovarian; stage: Children's Oncology
Group (COG) stage I, Federation of Gynecology and Obstetrics (FIGO) stage IA and IB;
grade: 2 or 3; histology: pure immature teratoma (may contain microscopic foci of yolk
sac tumor), mixed immature and mature teratoma, (no pathological evidence of MGCT);
tumor markers: alpha-FP =< 1,000 ng/mL, beta-HCG institutional normal; all ages
• Low risk stage I non-seminoma MGCT; site: ovarian, testicular, or extragonadal; stage:
COG stage I, FIGO stage IA and IB, American Joint Committee on Cancer (AJCC)
testicular stage IA, IB and IS; histology: must contain at least one of the following:
yolk sac tumor, embryonal carcinoma, or choriocarcinoma (pure or mixed); all ages
• Low risk stage I seminoma-MGCT; site: testicular; stage: COG stage I; AJCC testicular
stage IA IB, and IS; histology: must contain at least one of the following: may
contain immature/mature teratoma; may NOT contain yolk sac tumor, embryonal carcinoma,
or choriocarcinoma; all ages
• Standard risk 1 (SR1); site: ovarian, testicular, or extragonadal; stage: COG stage
II-IV, FIGO stage IC, FIGO stage II-IV (International Germ Cell Consensus
Classification [IGCCC] criteria DO NOT apply); histology: must contain at least one of
the following: yolk sac tumor, embryonal carcinoma, or choriocarcinoma; age (years) <
11
• Standard risk 2 (SR2)
• Site: ovarian; stage: COG stage II and III, FIGO stage IC, II and III; histology:
must contain at least one of the following: yolk sac tumor, embryonal carcinoma,
or choriocarcinoma; age (years) >= 11 and < 25
• Site: testicular; stage: COG stage II-IV, AJCC stage II, III, IGCCC good risk;
histology: must contain at least one of the following: yolk sac tumor, embryonal
carcinoma, or choriocarcinoma; tumor markers: must be IGCCC good risk; post op:
alpha-FP < 1,000 ng/mL, beta-HCG < 5,000 IU/mL and lactate dehydrogenase (LDH) <
3.0 x normal; age (years) >= 11 and < 25
• Site: extragonadal; stage: COG stage II; histology: must contain at least one of
the following: yolk sac tumor, embryonal carcinoma, or choriocarcinoma; age
(years) >= 11 and < 25
• Notes:
• IGCCC criteria only apply to SR2 patients with a testicular primary tumor
• Use post-op tumor marker levels to determine IGCCC risk group
• Stage 1 seminoma patients are not eligible for the standard risk arms of the
study
• For the low risk stage I non-seminoma MGCT and the standard risk arms, components
of yolk sac tumor, embryonal carcinoma, or choriocarcinoma can be mixed with
other forms of GCT, such as seminoma or mature or immature teratoma; if yolk sac
tumor is the only malignant component present, then it must be deemed by the
pathologist to be greater than a "microscopic component" of yolk sac tumor
• Patients must have a performance status corresponding to Eastern Cooperative Oncology
Group (ECOG) scores of 0, 1, 2 or 3; use Karnofsky for patients > 16 years of age and
Lansky for patients =< 16 years of age
• Organ function requirements apply ONLY to patients who will receive chemotherapy (SR1
and SR2 patients)
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70
mL/min/1.73 m^2
• A serum creatinine based on age/gender as follows: (mg/dL)
• 1 month to < 6 months male: 0.4 female: 0.4
• 6 months to < 1 year male: 0.5 female: 0.5
• 1 to < 2 years male: 0.6 female: 0.6
• 2 to < 6 years male: 0.8 female: 0.8
• 6 to < 10 years male: 1 female: 1
• 10 to < 13 years male: 1.2 female: 1.2
• 13 to < 16 years: male: 1.5 female: 1.4
• >= 16 years male: 1.7 female: 1.4
• Total bilirubin =< 1.5 x upper limit of normal (ULN) for age
• Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or
serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 2.5 x
upper limit of normal (ULN) for age (for the purpose of this study, the ULN for SGPT
is 45 U/L)
• Peripheral absolute neutrophil count (ANC) >= 1,000/mm^3
• Platelet count >= 100,000/mm^3
• Patients enrolling on the standard risk arms must be medically fit to receive protocol
treatment and with no contraindications to protocol treatment
• Eligibility criteria to participate in the pilot study of the AYA-Hears instrument
(patient reported outcomes [PROs] of ototoxicity) Note: participants in group 1 will
not receive AGCT1531 protocol-directed therapy; all other AYA-HEARS patients must be
enrolled on the AGCT1531 SR2 arm in order to participate
• >= 11 and < 25 years old at enrollment
• Able to fluently speak and read English
• Has received prior cisplatin- or carboplatin-based chemotherapy regimen for malignancy
including diagnoses other than germ cell tumor
• Followed for cancer or survivorship care at one of the following institutions:
• Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
• Dana Farber/Harvard Cancer Center
• Hospital for Sick Children
• Children's Hospital of Eastern Ontario
• Oregon Health and Science University
• Seattle Children's Hospital
• Yale University
Exclusion Criteria:
• Patients with any diagnoses not listed including:
• Stage I testicular cancer patients who have undergone primary RPLND
(retroperitoneal lymph node dissection)
• Pure dysgerminoma
• Pure mature teratoma
• Pure immature teratoma COG stage I, grade I
• Pure immature teratoma COG stage I, grade 2,3 with alpha-fetoprotein (AFP) >=
1000 ng/mL
• Pure immature teratoma COG stage II •IV or FIGO stage IC to IV
• "Poor risk" GCT (age >= 11 years old and COG stage IV ovarian, COG stage III or
IV EG, or IGCCC intermediate or poor risk testicular), or
• Primary central nervous system (CNS) germ cell tumor
• Germ cell tumor with somatic malignant transformation
• Spermatocytic seminoma
• Patients must have had no prior systemic therapy for the current cancer diagnosis
• Patients must have had no prior radiation therapy with the exception of CNS
irradiation of brain metastases; (this exception only applies to SR1 patients; any
patients over age 11 with distant metastases to brain [stage IV disease] would be
considered poor risk and therefore not eligible for this trial)
• Patients with significant, pre-existing co-morbid respiratory disease that
contraindicate the use of bleomycin, are ineligible for the standard risk arms of the
trial
• Female patients who are pregnant since fetal toxicities and teratogenic effects have
been noted for several of the study drugs; a pregnancy test is required for female
patients of childbearing potential; (this criteria applies ONLY to patients who will
receive chemotherapy [SR1 and SR2 patients])
• Lactating females who plan to breastfeed their infants; (this criteria applies ONLY to
patients who will receive chemotherapy [SR1 and SR2 patients])
• Sexually active patients of reproductive potential who have not agreed to use an
effective contraceptive method for the duration of their study participation; (this
criteria applies ONLY to patients who will receive chemotherapy [SR1 and SR2
patients])
Childhood Extracranial Germ Cell Tumor, Malignant Germ Cell Tumor, Germ Cell Tumor, Extragonadal Embryonal Carcinoma, Stage I Ovarian Choriocarcinoma, Stage II Ovarian Choriocarcinoma, Stage III Ovarian Choriocarcinoma, Stage IV Ovarian Choriocarcinoma, Testicular Mixed Choriocarcinoma and Embryonal Carcinoma, Testicular Mixed Choriocarcinoma and Teratoma, Testicular Mixed Choriocarcinoma and Yolk Sac Tumor, Stage I Testicular Choriocarcinoma AJCC v6 and v7, Stage I Testicular Embryonal Carcinoma AJCC v6 and v7, Stage I Testicular Yolk Sac Tumor AJCC v6 and v7, Stage II Testicular Choriocarcinoma AJCC v6 and v7, Stage II Testicular Embryonal Carcinoma AJCC v6 and v7, Stage II Testicular Yolk Sac Tumor AJCC v6 and v7, Stage III Testicular Choriocarcinoma AJCC v6 and v7, Stage III Testicular Embryonal Carcinoma AJCC v6 and v7, Stage III Testicular Yolk Sac Tumor AJCC v6 and v7, Malignant Ovarian Teratoma, Stage I Ovarian Embryonal Carcinoma AJCC v6 and v7, Stage I Ovarian Teratoma AJCC v6 and v7, Stage I Ovarian Yolk Sac Tumor AJCC v6 and v7, Stage II Ovarian Embryonal Carcinoma AJCC v6 and v7, Stage II Ovarian Yolk Sac Tumor AJCC v6 and v7, Stage III Ovarian Embryonal Carcinoma AJCC v6 and v7, Stage III Ovarian Yolk Sac Tumor AJCC v6 and v7, Stage IV Ovarian Embryonal Carcinoma AJCC v6 and v7, Stage IV Ovarian Yolk Sac Tumor AJCC v6 and v7, Other Female Genital, Other Male Genital, Ovary, Unknown Sites, Stage I Testicular Seminoma AJCC v6 and v7
UT Southwestern; Children’s Health; Parkland Health & Hospital System
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.
Pegylated Liposomal Doxorubicin Hydrochloride With Atezolizumab and/or Bevacizumab in Treating Patients With Recurrent Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
This phase II/III trial studies how well pegylated liposomal doxorubicin hydrochloride with
atezolizumab and/or bevacizumab work in treating patients with ovarian, fallopian tube, or
primary peritoneal cancer that has come back (recurrent). Chemotherapy drugs, such as
pegylated liposomal doxorubicin hydrochloride, 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. Immunotherapy with monoclonal antibodies, such as atezolizumab and
bevacizumab, may help the body's immune system attack the cancer, and may interfere with the
ability of tumor cells to grow and spread. It is not yet known which combination will work
better in treating patients with ovarian, fallopian tube, or primary peritoneal cancer.
• Patients must have the psychological ability and general health that permits
completion of the study requirements and required follow up
• Administration of study drugs (pegylated liposomal doxorubicin, bevacizumab,
atezolizumab) may have an adverse effect on pregnancy and poses a risk to the human
fetus, including embryo-lethality; women of child-bearing potential (WOCBP) must agree
to use adequate contraception (hormonal or barrier method of birth control;
abstinence) prior to study entry, for the duration of study participation, and for 5
months (150 days) after the last dose of study agent; should a woman become pregnant
or suspect she is pregnant while she is participating in this study, she should inform
her treating physician immediately. (06/29/2017)
• Submission of tumor tissue is required for all patients; investigators should check
with their site pathology department regarding release of biospecimens before
approaching patients about participation in the trial
• High grade ovarian cancer, including high grade serous; clear cell; endometrioid,
grade 3; and others (adenocarcinoma, not otherwise specified [NOS]; mixed epithelial
carcinoma; undifferentiated carcinoma); NOTE: low grade serous, mucinous and
carcinosarcoma histologies are excluded due to their different underlying genomic
features and/or clinical behavior; ovarian cancer = ovarian, fallopian tube or primary
peritoneal cancer; required data element: submission of pathology report
• Recurrent, platinum resistant ovarian cancer (defined as progression within < 6 months
from completion of platinum based therapy; the date should be calculated from the last
administered dose of platinum therapy)
• 1-2 prior regimens (including primary therapy); hormonal therapies (e.g., tamoxifen,
aromatase inhibitors) will not count toward the prior regimen limit; PARP inhibitors
given in the maintenance setting post response to platinum-based therapy will not
count as a separate regimen from the preceding platinum-based therapy. (30-OCT-2020)
• Measurable disease (defined by RECIST v1.1) or evaluable disease (defined as solid
and/or cystic abnormalities on radiographic imaging that do not meet RECIST 1.1
definitions for target lesions OR ascites and/or pleural effusion that has been
pathologically demonstrated to be disease related in the setting of cancer antigen
[CA] 125 >= 2 x upper limit of normal [ULN])
• Performance status 0, 1 or 2
• Absolute neutrophil count (ANC) >= 1,500/mcl (within 14 days prior to registration)
• Platelets >= 100,000/mcl (within 14 days prior to registration)
• Hemoglobin (Hgb) >= 8 g/dl (within 14 days prior to registration)
• Creatinine =< 1.5 x institutional upper limit of normal (ULN) (within 14 days prior to
registration)
• Urine protein creatinine (UPC) ratio must be < 1.0 (within 14 days prior to
registration); if UPC ratio >= 1, collection of 24-hour urine measurement of urine
protein is recommended (24-hour urine protein level must be < 1000 mg for patient
enrollment); If UPC ratio cannot be calculated because the urine protein is below the
lower limit of detection of the assay this will not exclude the patient (10/22/2018)
(30-OCT-2020); UPC ratio of spot urine is an estimation of the 24-hour urine protein
excretion •a UPC ratio of 1 is roughly equivalent to a 24-hour urine protein of 1 gm
• Total bilirubin =< 1.5 x ULN (patients with known Gilbert disease who have serum
bilirubin level =< 3 x ULN may be enrolled) (within 14 days prior to registration)
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3 x ULN (AST and/or
ALT =< 5 x ULN for patients with liver involvement) (within 14 days prior to
registration)
• International normalized ratio (INR) and activated partial thromboplastin time (aPTT)
=< 1.5 x ULN (or on stable dose of therapeutic anticoagulation, such as
low-molecular-weight heparin, warfarin or rivaroxaban) (10/16/2017)
• Thyroid-stimulating hormone (TSH) within normal limits (Euthyroid patients on thyroid
replacement therapy allowed provided TSH < ULN) (02/20/2019)
• The patient or legally authorized representative must provide study-specific informed
consent prior to study entry and, for patients treated in the United States (U.S.),
authorization permitting release of personal health information
Exclusion Criteria:
• Patients with prior allogeneic bone marrow transplantation or prior solid organ
transplantation
• Patients who have had systemic anticancer therapy (e.g., chemotherapy, targeted
therapy including PARP inhibitors or bevacizumab) within 3 weeks prior to entering the
study (30-OCT-2020)
• Patients who have had hormonal therapy (e.g., tamoxifen, aromatase inhibitor) within 1
week prior to entering the study
• Patients with prior treatment with anti-programmed cell death (PD)-1, anti- programmed
cell death ligand (PD-L)1 or anti-cytotoxic T-lymphocyte-associated protein (CTLA)-4
therapeutic antibody or other similar agents (10/16/2017)
• Patients with prior treatment with bevacizumab (or any other anti vascular therapy,
e.g., cediranib) for platinum resistant recurrence; (Note: prior bevacizumab in
initial therapy and/or platinum sensitive recurrent setting is allowed)
• Patients with prior treatment with PLD
• Prior radiotherapy to the abdomen or pelvis
• Patients who have not recovered from adverse events to =< grade 1 (other than
alopecia) due to agents administered more than 3 weeks earlier (10/16/2017); however,
the following therapies are allowed:
• Hormone replacement therapy or oral contraceptives
• Herbal therapy > 1 week prior to cycle 1, day 1 (herbal therapy intended as
anticancer therapy must be discontinued at least 1 week prior to cycle 1, day 1)
• Palliative radiotherapy for bone metastases > 2 weeks prior to cycle 1, day 1
• Treatment with any other investigational agent within 4 weeks prior to cycle 1, day 1
• Treatment with systemic immunostimulatory agents (including, but not limited to,
interferon [IFN]-alpha or interleukin [IL]-2) within 6 weeks prior to cycle 1, day 1
• Treatment with systemic immunosuppressive medications (including, but not limited to,
prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor
necrosis factor [anti-TNF] agents) within 2 weeks prior to cycle 1, day 1
• Patients who have received acute, low dose, systemic immunosuppressant
medications (e.g., a one-time dose of dexamethasone for nausea or steroids as
computed tomography [CT] scan contrast premedication) may be enrolled
• The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone)
for patients with orthostatic hypotension or adrenocortical insufficiency is
allowed
• Patients taking bisphosphonate therapy for symptomatic hypercalcemia within the past
28 days; use of bisphosphonate therapy for other reasons (e.g., bone metastasis or
osteoporosis) is allowed
• Patients with known primary central nervous system (CNS) malignancy or symptomatic CNS
metastases are excluded, with the following exceptions:
• Patients with asymptomatic untreated CNS disease may be enrolled, provided all of
the following criteria are met:
• Evaluable or measurable disease outside the CNS
• No metastases to brain stem, midbrain, pons, medulla, cerebellum, or within
10 mm of the optic apparatus (optic nerves and chiasm)
• No history of intracranial hemorrhage or spinal cord hemorrhage
• No ongoing requirement for dexamethasone for CNS disease; patients on a
stable dose of anticonvulsants are permitted
• No neurosurgical resection or brain biopsy within 28 days prior to cycle 1,
day 1
• Patients with asymptomatic treated CNS metastases may be enrolled, provided all
the criteria listed above are met as well as the following:
• Radiographic demonstration of improvement upon the completion of CNS
directed therapy and no evidence of interim progression between the
completion of CNS directed therapy and the screening radiographic study
• No stereotactic radiation or whole-brain radiation within 28 days prior to
cycle 1, day 1
• Screening CNS radiographic study >= 4 weeks from completion of radiotherapy
and >= 2 weeks from discontinuation of corticosteroids
• Known hypersensitivity to Chinese hamster ovary cell products or other recombinant
human antibodies
• History of severe allergic, anaphylactic, or other hypersensitivity reactions to
chimeric or humanized antibodies or fusion proteins
• Patients requiring treatment with a receptor activator of nuclear factor kappa-B
ligand (RANKL) inhibitor (e.g. denosumab) who cannot discontinue it before treatment
with atezolizumab
• Known clinically significant liver disease, including active viral, alcoholic, or
other hepatitis; cirrhosis; fatty liver; and inherited liver disease
• Patients with past or resolved hepatitis B infection (defined as having a
negative hepatitis B surface antigen [HBsAg] test and a positive anti-HBc
[antibody to hepatitis B core antigen] antibody test) are eligible
• Patients positive for hepatitis C virus (HCV) antibody are eligible only if
polymerase chain reaction (PCR) is negative for HCV ribonucleic acid (RNA)
• History or risk of autoimmune disease, including but not limited to systemic lupus
erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis
associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjogren's
syndrome, Guillain-Barre syndrome, multiple sclerosis, autoimmune thyroid disease,
vasculitis, or glomerulonephritis (02/20/2019)
• Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid
replacement hormone are eligible
• Patients with controlled type 1 diabetes mellitus on a stable insulin regimen, or
type 2 diabetes mellitus are eligible
• Patients with eczema, psoriasis, lichen simplex chronicus or vitiligo with
dermatologic manifestations only (e.g., patients with psoriatic arthritis would
be excluded) are permitted provided that they meet the following conditions:
• Patients with psoriasis must have a baseline ophthalmologic exam to rule out
ocular manifestations
• Rash must cover less than 10% of body surface area (BSA)
• Disease is well controlled at baseline and only requiring low potency
topical steroids (e.g., hydrocortisone 2.5%, hydrocortisone butyrate 0.1%,
fluocinolone 0.01%, desonide 0.05%, alclometasone dipropionate 0.05%)
• No acute exacerbations of underlying condition within the last 12 months
(not requiring psoralen plus ultraviolet A radiation [PUVA], methotrexate,
retinoids, biologic agents, oral calcineurin inhibitors; high potency or
oral steroids)
• History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced),
organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing
pneumonia, etc.), or evidence of active pneumonitis on screening chest computed
tomography (CT) scan; history of radiation pneumonitis in the radiation field
(fibrosis) is permitted
• Patients with active tuberculosis (TB) are excluded
• Severe infections within 4 weeks prior to cycle 1, day 1, including but not limited to
hospitalization for complications of infection, bacteremia, or severe pneumonia
• Signs or symptoms of infection within 2 weeks prior to cycle 1, day 1
• Received oral or intravenous (IV) antibiotics within 2 weeks prior to cycle 1, day 1;
patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract
infection or chronic obstructive pulmonary disease) are eligible
• Major surgical procedure within 28 days prior to cycle 1, day 1 or anticipation of
need for a major surgical procedure during the course of the study
• Administration of a live, attenuated vaccine within 4 weeks before cycle 1, day 1 or
anticipation that such a live, attenuated vaccine will be required during the study
and up to 5 months after the last dose of atezolizumab (06/29/2017)
• Influenza vaccination should be given during influenza season only (approximately
October to March); patients must not receive live, attenuated influenza vaccine
within 4 weeks prior to cycle 1, day 1 or at any time during the study
• 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
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral
therapy with undetectable viral load within 6 months are eligible for this trial
(08-JAN-2021)
• Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free
for a minimum of 3 years, with the exception of those with a negligible risk of
metastases or death, such as carcinoma in situ of the breast or cervix
• Severe, active co-morbidity defined as follows:
• Current (within 28 days of cycle 1, day 1) signs and/or symptoms of bowel
obstruction
• Patients who require parental hydration and/or nutrition
• Patients who require drainage gastrostomy tube
• Evidence of bleeding diathesis or clinically significant coagulopathy
• Serious, non-healing or dehiscing wound, active ulcer or untreated bone fracture
• History of hemoptysis (>= 1/2 teaspoon of bright red blood per episode) within 1
month of study enrollment
• Significant cardiovascular or cerebrovascular disease including:
• Uncontrolled hypertension (systolic blood pressure [SBP] >= 150 and/or diastolic
blood pressure [DBP] >= 90)
• History of myocardial infarction within 6 months
• Unstable angina
• New York Heart Association functional classification II, III or IV
• Baseline ejection fraction =< 50% as assessed by echocardiogram or multi-gated
acquisition (MUGA)
• Cerebral vascular accident (CVA) or transient ischemic attack (TIA) within 6
months
• Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or
peripheral arterial thrombosis) within 6 months
• History of abdominal/pelvic or tracheoesophageal fistula or gastrointestinal
perforation and/or abdominal/pelvic abscess within 6 months prior to initiation of
treatment (02/20/2019)
• Pregnant or lactating patients
A Study to Evaluate ONM-100, an Intraoperative Fluorescence Imaging Agent for the Detection of Cancer
This study is to evaluate diagnostic performance, safety and timing of post-dose imaging of
ONM-100, an intraoperative fluorescence imaging agent for the detection of cancer in patients
with solid tumors undergoing routine surgery.
• Biopsy-confirmed diagnosis of primary or recurrent respective tumor type and scheduled
to undergo surgical resection
• Part 1: Biopsy-confirmed diagnosis of head and neck squamous cell carcinoma (HNSCC) or
breast cancer
• Part 2: Biopsy-confirmed diagnosis of HNSCC, breast cancer, colorectal cancer,
prostate cancer, ovarian cancer, urothelial carcinoma and non-small cell lung cancer.
• Part 3: Stage 2 to 4 HNSCC Including T0 or Tx unknown Primary cancers
Exclusion Criteria:
• Histologically diagnosed by an excisional biopsy procedure
• Tumors at sites of which the surgeon would assess that in vivo intraoperative imaging
would not be feasible
• Life expectancy <12 weeks
• Hepatic impairment (Child-Pugh score >5) or significant liver disease including active
hepatitis or cirrhosis
Drug: ONM-100
Prostate Cancer, Non-Small Cell Lung Cancer, Breast Cancer, Colorectal Cancer, Ovarian Cancer, Head and Neck Squamous Cell Carcinoma, Urothelial Carcinoma, Breast - Female, Colon, Ovary, Prostate
1. Have histologically confirmed advanced or metastatic castration-resistant prostate
cancer, bladder cancer, melanoma, non-small cell lung cancer, pancreatic cancer,
colorectal cancer, gastric cancer, esophageal cancer, ovarian cancer, and head neck
squamous cell carcinoma.
Or,
Have histologically confirmed metastatic pancreatic adenocarcinoma. Recurrent
unresectable pancreatic cancer is acceptable as long as the treatment is first-line.
2. Have not received any approved chemotherapy, except in the adjuvant setting.
Exclusion Criteria:
1. Subject was using immunosuppressive medications within 14 days before Screening with
the exception of topical (intranasal, inhaled, and local injection), systemic
(prednisone equivalent 10 mg/day or less), or as needed for hypersensitivity reactions
such as computed tomography (CT) scan premedication.
2. Subject has active infections or other serious underlying significant medical illness,
abnormal and clinically significant laboratory findings or psychiatric illness/social
situation.
3. Subject is using a pacemaker, implantable cardiac defibrillator, neurostimulator,
cochlear implants, cochlear implants, or other electronic medical equipment.
4. Subject has documented immunodeficiency or organ transplant.
5. Subject has an untreated central nervous system disease, leptomeningeal disease or
cord compression.
6. Subject has a history, or presence, of significant cardiovascular diseases; including
uncontrolled hypertension, clinically relevant cardiac arrhythmia, unstable angina or
myocardial infarction within 6 months before randomization, congestive heart failure >
New York Heart Association Class II, severe peripheral vascular disease, corrected QT
(QTc) prolongation >470 msec, clinically significant pericardial effusion.
7. Subject has a history or presence of documented inflammatory bowel disease.
8. Subject is known to be positive for human immunodeficiency virus infection.
-