Clinical Trials /

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

NCT03355976

Description:

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.

Related Conditions:
  • Clear Cell Adenocarcinoma
  • Fallopian Tube Carcinoma
  • Ovarian Clear Cell Adenocarcinoma
  • Primary Peritoneal Clear Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: BrUOG 354
  • NCT ID: NCT03355976

Conditions

  • Ovarian Cancer
  • Fallopian Tube Cancer
  • Primary Peritoneal Carcinoma
  • Extra Renal Origin
  • Clear Cell Adenocarcinoma

Interventions

DrugSynonymsArms
NivolumabArm 1 Nivolumab Ovarian
IpilimumabArm 2 Nivolumab and Ipilimumab Ovarian

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Arm 1 Nivolumab OvarianExperimentalNivolumab 240 mg Day 1 Cycle = 2 weeks
  • Nivolumab
Arm 2 Nivolumab and Ipilimumab OvarianExperimentalNivolumab 240 mg every 2 weeks Ipilimumab 1mg/kg day 1 Cycle=6 weeks
  • Nivolumab
  • Ipilimumab
Arm 1 Nivolumab Extra-renalExperimentalNivolumab 240 mg Day 1 Cycle = 2 weeks
  • Nivolumab
Arm 2 Nivolumab and Ipilimumab Extra-renalExperimentalNivolumab 240 mg every 2 weeks Ipilimumab 1mg/kg day 1 Cycle=6 weeks
  • Nivolumab
  • Ipilimumab

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 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 investigational
             product.

          -  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 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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.
Safety Issue:
Description: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

Measure: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.
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Don Dizon

Trial Keywords

  • recurrent
  • advanced
  • metastatitic

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