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BrUOG 354 Nivolumab +/- Ipilimumab for Ovarian and Extra-renal Clear Cell Carcinomas

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03355976
Recruitment Status : Recruiting
First Posted : November 29, 2017
Last Update Posted : August 3, 2020
Sponsor:
Collaborators:
Bristol-Myers Squibb
Rhode Island Hospital
The Miriam Hospital
Brown University
Women and Infants Hospital of Rhode Island
Information provided by (Responsible Party):
Don Dizon, Brown University

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.

Condition or disease Intervention/treatment Phase
Ovarian Cancer Fallopian Tube Cancer Primary Peritoneal Carcinoma Extra Renal Origin Clear Cell Adenocarcinoma Drug: Nivolumab Drug: Ipilimumab Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 62 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: BrUOG 354: A Phase II Randomized Trial of Nivolumab +/- Ipilimumab for Ovarian and Extra-renal Clear Cell Carcinomas
Actual Study Start Date : April 30, 2018
Estimated Primary Completion Date : February 2021
Estimated Study Completion Date : February 2023


Arm Intervention/treatment
Experimental: Arm 1 Nivolumab Ovarian
Nivolumab 240 mg Day 1 Cycle = 2 weeks
Drug: Nivolumab
240mg flat dose every 2 weeks

Experimental: Arm 2 Nivolumab and Ipilimumab Ovarian
Nivolumab 240 mg every 2 weeks Ipilimumab 1mg/kg day 1 Cycle=6 weeks
Drug: Nivolumab
240mg flat dose every 2 weeks

Drug: Ipilimumab
Ipilimumab 1mg/kg every 6 weeks

Experimental: Arm 1 Nivolumab Extra-renal
Nivolumab 240 mg Day 1 Cycle = 2 weeks
Drug: Nivolumab
240mg flat dose every 2 weeks

Experimental: Arm 2 Nivolumab and Ipilimumab Extra-renal
Nivolumab 240 mg every 2 weeks Ipilimumab 1mg/kg day 1 Cycle=6 weeks
Drug: Nivolumab
240mg flat dose every 2 weeks

Drug: Ipilimumab
Ipilimumab 1mg/kg every 6 weeks




Primary Outcome Measures :
  1. 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 [ Time Frame: Every 8 weeks during treatment then every 12 weeks in follow-up for up to 2 years (once off study) and until progression. ]
    RECIST 1.1 and immune mediated RECIST. Confirmatory scans are required. Patients may remain on study post initial progression, but are required to be removed from treatment if they progress an additional 10%.


Secondary Outcome Measures :
  1. Compare median PFS for patients treated with nivolumab (Arm 1) and the combination of nivolumab and ipilimumab (Arm 2) [ Time Frame: To be assessed throughout the trial, but specifically at the DSMB meetings bi-annually and after follow-up has been completed. Follow-up is for up to 2 years post last treatment. ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 <grade 2 and which are related to prior treatment agents administered.
  • Participants who are receiving any other investigational agents.
  • Participants with known brain metastases are excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
  • History of severe hypersensitivity reaction to any monoclonal antibody.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring antibiotics, symptomatic congestive heart failure, unstable angina pectoris, serious cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Pregnant women are excluded from this study
  • Patients with a history of other invasive malignancies, with the exception of non-melanoma skin cancer are excluded if there is any evidence of other malignancy being present within the last three years. However, patients with a malignancy that is not-likely to require treatment in the next 2 years, such as a completely resected, early stage breast cancer, are eligible.
  • Patients who have received prior chemotherapy within the last three years for any other cancer other than for clear cell cancer.
  • In order for patients with known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) to be eligible, they must be on a stable highly active antiretroviral therapy (HAART) regimen, have CD4 counts > 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03355976


Contacts
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Contact: Roxanne Wood, BA 401-863-3000 roxanne_wood@brown.edu

Locations
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United States, Rhode Island
Rhode Island Hospital Recruiting
Providence, Rhode Island, United States, 02903
Contact: Roxanne Wood, BA    401-863-3000    roxanne_wood@brown.edu   
Contact: Amy Webber, BA    4018633000    Amy_Webber@brown.edu   
Principal Investigator: Don Dizon, MD         
Women & Infants Hospital Recruiting
Providence, Rhode Island, United States, 02905
Contact: Roxanne L Wood, BA    401-863-3000    roxanne_wood@brown.edu   
Contact: Amy Webber, BA    4018633000    Amy_Webber@brown.edu   
Principal Investigator: Katina Robison, MD         
The Miriam Hospital Recruiting
Providence, Rhode Island, United States, 02906
Contact: Roxanne Wood, BA    401-863-3000    roxanne_wood@brown.edu   
Contact: Amy Webber, BA    4018633000    Amy_Webber@brown.edu   
Principal Investigator: Don Dizon, MD         
Sponsors and Collaborators
Don Dizon
Bristol-Myers Squibb
Rhode Island Hospital
The Miriam Hospital
Brown University
Women and Infants Hospital of Rhode Island
Investigators
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Principal Investigator: Don Dizon, MD Brown University Oncology Research Group (BrUOG) & Lifespan Cancer Institute
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Responsible Party: Don Dizon, Principal Investigator, Brown University
ClinicalTrials.gov Identifier: NCT03355976    
Other Study ID Numbers: BrUOG 354
First Posted: November 29, 2017    Key Record Dates
Last Update Posted: August 3, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Don Dizon, Brown University:
recurrent
advanced
metastatitic
Additional relevant MeSH terms:
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Carcinoma
Fallopian Tube Neoplasms
Adenocarcinoma, Clear Cell
Adenomyoepithelioma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Neoplasms by Site
Adnexal Diseases
Genital Neoplasms, Female
Urogenital Neoplasms
Fallopian Tube Diseases
Neoplasms, Complex and Mixed
Nivolumab
Ipilimumab
Antineoplastic Agents, Immunological
Antineoplastic Agents