Brief Title
BrUOG 354 Nivolumab +/- Ipilimumab for Ovarian and Extra-renal Clear Cell Carcinomas
Official Title
BrUOG 354: A Phase II Randomized Trial of Nivolumab +/- Ipilimumab for Ovarian and Extra-renal Clear Cell Carcinomas
Brief Summary
Preclinical and early-phase clinical data suggest that immune modulation represents a
treatment strategy that is worthy of further investigation in relapsed epithelial ovarian
cancer. One method by which tumor cells may evade immune surveillance is by activation of the
programmed cell death (PD-1) pathway, mediated by expression of PD-1 on the surface of T
lymphocytes, which conveys an inhibitory signal after binding to its ligand PD-L1 on the
surface of tumor cells. Nivolumab and Ipilimumab have shown activity as monotherapies in
solid tumors and very early data suggest that nivolumab may be particularly active for
ovarian clear cell carcinoma.(Hamanishi et al., 2015). Given the uniformly poor prognosis for
patients with clear cell carcinoma in general, we are interested in formally evaluating this
agent in all extra-renal clear cell carcinomas.
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
Proportion of patients who have objective tumor response (complete or partial) by modified RECIST 1.1 in patients with clear cell carcinomas treated with nivolumab or the combination of nivolumab and ipilimumab
Secondary Outcome
Compare median PFS for patients treated with nivolumab (Arm 1) and the combination of nivolumab and ipilimumab (Arm 2)
Condition
Ovarian Cancer
Intervention
Nivolumab
Study Arms / Comparison Groups
Arm 1 Nivolumab Ovarian
Description: Nivolumab 240 mg Day 1 Cycle = 2 weeks
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
62
Start Date
April 30, 2018
Completion Date
February 2023
Primary Completion Date
December 2021
Eligibility Criteria
Inclusion Criteria:
- Patients must have a recurrent, advanced, or metastatic pure clear cell carcinoma of
ovarian, fallopian tube, primary peritoneal, or extra-renal origin.
- All patients must submit representative tissue from their malignancy.
- Participants must have measurable disease, defined as at least one lesion that can be
accurately measured in at least one dimension (longest diameter to be recorded for
non-nodal lesions and short axis for nodal lesions) as ≥20 mm with conventional
techniques or as ≥10 mm with spiral CT scan, MRI, or calipers by clinical exam.
- Patients with a clear cell carcinoma of ovarian, fallopian or primary peritoneal
origin must have progressed after at least one prior platinum and taxane based
chemotherapy regimen. Patients with extra-renal clear cell cancer (including other
GYN) cancers must have progressed after at least one prior regimen for
advanced/metastatic disease. Radiation therapy (including the use of chemotherapy as a
radiosensitizer) will not count as a prior systemic regimen.
- No prior anti-PD-1, PD-L1 or CTLA-4 antibody.
- Age ≥ 18
- ECOG performance status 0 to 1
- Participants must have normal organ and marrow function as defined below:
leukocytes ≥3,000/mcL absolute neutrophil count ≥1,500/mcL platelets ≥100,000/mcL total
bilirubin within normal institutional limits EXCEPTIONS: conjugated hyperbilirubinemia;
Gilbert's syndrome, both of which will allow a total bilirubin <3.0mg/dL <5xULN is liver
metastases are present A value below the LLN is acceptable if confirmed appropriate by the
treating MD AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal creatinine ≤ 1.5
X ULN (upper limit of normal) OR creatinine clearance ≥50 mL/min
- Adequate thyroid function within 28 days prior to registration defined as serum TSH in
normal range. Patients on thyroid hormone supplementation are allowed provided the
serum TSH is within normal limits.
- Subjects must have a resting baseline O2 saturation by pulse oximetry of ≥92% at rest.
This should be documented within two weeks of registration.
- Reproductive status:
- Women of childbearing potential (WOCBP) must use method(s) of contraception. Given
there is insufficient information to assess teratogenicity (preclinical studies have
not been done), a highly effective method(s) of contraception (failure rate of less
than 1% per year) is required as determined by the treating investigator. WOCBP must
follow instructions for birth control. For all women who discontinue protocol
treatment, contraception should be continued for five months following the last dose
of therapy.
- WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L
or equivalent units of HCG) within 7 days prior to the start of registration.
- Women who are not of childbearing potential (ie, who are postmenopausal (lack of
menses > 24 months) or surgically sterile) and azospermic men do not require
contraception.
- Women must not be breastfeeding (document for all).
- Men who are sexually active with WOCBP must use any contraceptive method with a
failure rate of less than 1 % per year. The investigator shall review contraception
methods and the time period that contraception must be followed.
- Men that are sexually active with WOCBP must follow instructions for birth control
when the half life of the investigational drug is greater than 24 hours, contraception
should be continued for a period of 7 months after discontinuation of treatment.
- Ability to understand and the willingness to sign a written informed consent document.
Exclusion Criteria:
- Participants who have had prior therapy with nivolumab or with an anti-PD-1,
anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug
specifically targeting T-cell co-stimulation or immune check point pathways.
- Participants who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
nitrosoureas or mitomycin C) prior to entering the study. Patients using endocrine
therapy as treatment for their index cancer must be off of treatment for one week (7
days) prior to entering the study.
- Participants who have not recovered from clinically significant adverse events to
350, with no detectable viral load on quantitative PCR
within 4 weeks of registration.
- Patients with treated hepatitis virus infections (Hepatitis B or Hepatitis C) are
eligible if they have been definitively treated for 6 months, have no detectable viral
load on quantitative PCR, and LFTs meet eligibility requirements within 4 weeks of
screening.
- 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, should be excluded.
- Patients should be excluded if they have a condition requiring systemic treatment with
either corticosteroids (>10 mg daily prednisone equivalents) or other
immunosuppressive medications within 14 days of day 1 study drug administration.
- Any other medical condition that will prevent the safe administration of study drugs
in the opinion of the treating physician.
- Planned concomitant, non-protocol directed anti-cancer therapy during the trial.
- Grade ≥2 peripheral neuropathy
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Don Dizon, MD, 401-863-3000, [email protected]
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT03355976
Organization ID
BrUOG 354
Responsible Party
Sponsor-Investigator
Study Sponsor
Don Dizon
Collaborators
Bristol-Myers Squibb
Study Sponsor
Don Dizon, MD, Principal Investigator, Brown University Oncology Research Group (BrUOG) & Lifespan Cancer Institute
Verification Date
August 2021