Clinical Trials /

NIMBUS: Nivolumab Plus Ipilimumab in Metastatic Hypermutated HER2-negative Breast Cancer

NCT03789110

Description:

This research study is studying a drug combination of nivolumab and ipilimumab as a possible treatment for hypermutated HER2 negative breast cancer. The drugs involved in this study are: - Nivolumab (Opdivo ®) - Ipilimumab (Yervoy ®)

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: NIMBUS: A Phase II Study of Nivolumab Plus Ipilimumab in Metastatic Hypermutated HER2-negative Breast Cancer
  • Official Title: NIMBUS: A Phase II Study of Nivolumab Plus Ipilimumab in Metastatic Hypermutated HER2-negative Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: 18-561
  • NCT ID: NCT03789110

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
NivolumabOpdivoNivolumab+Ipilimumab
IpilimumabYervoyNivolumab+Ipilimumab

Purpose

This research study is studying a drug combination of nivolumab and ipilimumab as a possible treatment for hypermutated HER2 negative breast cancer. The drugs involved in this study are: - Nivolumab (Opdivo ®) - Ipilimumab (Yervoy ®)

Detailed Description

      This research study is a Phase II clinical trial. Phase II clinical trials test the safety
      and effectiveness of an investigational drug to learn whether the drug works in treating a
      specific disease. "Investigational" means that the drug is being studied.

      Nivolumab is called an anti- PD-1 or a checkpoint inhibitor and is an antibody (a type of
      human protein) designed to allow the body's own immune system to destroy tumors. Ipilimumab
      is called an anti-CTLA-4 and is a type of antibody that works to prevent your body's immune
      system from stopping to fight this specific cancer.

      The U.S. Food and Drug Administration (FDA) has not approved nivolumab for this specific
      disease but it has been approved for other uses including but not limited to non-small cell
      lung cancer, melanoma and renal cell carcinoma.

      The U.S. Food and Drug Administration (FDA) has not approved ipilimumab for this specific
      disease but it has been approved for other uses such as melanoma and renal cell carcinoma.

      The combination of nivolumab with ipilimumab may or may not increase anti-cancer activity by
      further boosting the immune system. At this time, the FDA has not approved nivolumab in
      combination with ipilimumab for this specific disease although these drugs have been approved
      for other uses such as melanoma and renal cell carcinoma.

      The purpose of this research study is to determine how nivolumab together with ipilimumab,
      works in treating breast cancer that has spread to other parts of the body. The investigators
      are also investigating whether there are certain DNA or protein markers in the blood or tumor
      tissue that may indicate whether the combination will work in future patients
    

Trial Arms

NameTypeDescriptionInterventions
Nivolumab+IpilimumabExperimentalIpilimumab is administered intravenously every 6 weeks Nivolumab is administered intravenously every 2 weeks
  • Nivolumab
  • Ipilimumab

Eligibility Criteria

        Inclusion Criteria:

          -  Participants must have histologically or cytologically confirmed invasive breast
             cancer, with metastatic disease. Participants without pathologic or cytologic
             confirmation of metastatic disease should have unequivocal evidence of metastasis from
             physical examination or radiologic evaluation.

          -  Breast cancer must be HER2-negative by IHC or non-amplified as determined by the
             current ASCO-CAP criteria. If patient has more than one histological result, the most
             recent one will be usedfor inclusion. Participants may be ER/PR positive or negative.

          -  Patients must harbor tumors with total mutational burden of at least 10 mutations per
             megabase assessed by a cancer-gene panel containing more than 300 genes, and performed
             in a CLIA verified laboratory. Tests like Foundation One, Oncopanel (DFCI), or IMPACT
             (MSKCC) are acceptable for including patients on this trial.

          -  Participants must have measurable disease by RECIST version 1.1.

          -  Participants must agree to undergo a research biopsy, if tumor is safely accessible,
             at baseline and at day 29 cycle 1 (+14 scheduling window). Participants for whom
             newly-obtained samples cannot be provided (e.g. inaccessible or participant safety
             concern) may submit an archived specimen (block or if not possible, 20 unstained
             slides).

          -  Prior chemotherapy: Participants may have received 0-3 prior chemotherapeutic regimens
             for metastatic breast cancer and must have been off treatment with chemotherapy for at
             least 14 days prior to study treatment initiation.

          -  Patients with hormone receptor positive breast cancer must have progressed on at least
             one prior line of endocrine therapy in the metastatic setting or have disease
             recurrence while on adjuvant endocrine therapy.

          -  Participants should also be adequately recovered from acute toxicities of prior
             treatment, with the exception of alopecia and peripheral sensory neuropathy.

          -  Prior biologic therapy: Patients must have discontinued all biologic therapy at least
             14 days prior to study treatment initiation.

          -  Prior radiation therapy: Patients may have received prior radiation therapy in either
             the metastatic or early-stage setting. Radiation therapy must be completed 14 days
             prior to study treatment initiation.

          -  In all cases, there must be no ongoing complications from prior radiotherapy.

          -  The subject is ≥18 years old.

          -  ECOG performance status ≤1(Karnofsky ≥70%, see Appendix A).

          -  Participants must have normal organ and marrow function as defined below:

               -  absolute neutrophil count ≥1,000/mcL

               -  platelets ≥100,000/mcL

               -  hemoglobin ≥ 8 g/dl

               -  total bilirubin ≤1.5 × institutional upper limit of normal (ULN) (or ≤ 2.0 x ULN
                  in patients with documented Gilbert's Syndrome)

               -  AST(SGOT)/ALT(SGPT) ≤2.5 × institutional ULN or (≤ 3 × institutional ULN for
                  participants with documented liver metastases)

               -  creatinine ≤1.5 × institutional ULN OR creatinine clearance ≥ 40 mL/min (using
                  Cockcroft-Gault formula) for participants with creatinine levels above
                  institutional ULN.

          -  Female subjects of childbearing potential must have a negative pregnancy test (serum
             or urine) at screening.

          -  Childbearing potential is defined as: participants who have not reached a
             postmenopausal state (≥ 12 continuous months of amenorrhea with no identified cause
             other than menopause) and has not undergone surgical sterilization (removal of ovaries
             and/or uterus).

          -  Female and male participants of childbearing potential must agree to use an adequate
             method of contraception. For women, contraception is required starting with the first
             dose of study medication through 150 days (5 months) after the last dose of study
             medication. For men who are sexuall active with women of childbearing potential,
             contraception is required starting with the first dose of study medication for a
             period of 7 months after the last dose of nivolumab. Examples of contraceptive methods
             with a failure rate of < 1% per year include bilateral tubal ligation, male
             sterilization, established and proper use of hormonal contraceptives that inhibit
             ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices.
             The reliability of sexual abstinence should be evaluated in relation to the duration
             of the clinical trial and the preferred and usual lifestyle of the patient. Periodic
             abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and
             withdrawal are not acceptable methods of contraception.

          -  Participants on bisphosphonates may continue receiving bisphosphonate therapy during
             study treatment. Initiation of bisphosphonate or RANKL agent is allowed on study.

          -  The participant is capable of understanding and complying with the protocol and has
             signed the informed consent document.

        Exclusion Criteria:

          -  Major surgery within 2 weeks before the first dose of study treatment.

          -  Concurrent administration of other anti-cancer therapy within 14 days of starting
             protocol therapy and during the course of this study.

          -  The participant has received another investigational agent within 14 days of the first
             dose of study drug.

          -  Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, or
             anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody.

          -  Known brain metastases that are untreated, symptomatic, or require therapy to control
             symptoms. Participants with a history of treated central nervous system (CNS)
             metastases are eligible. Treated brain metastases are defined as those having no
             evidence of progression for ≥ 2 weeks after treatment, and no ongoing requirement for
             corticosteroids, as ascertained by clinical examination and brain imaging (magnetic
             resonance imaging or CT scan) completed during screening. Subject must be either off
             corticosteroids, or on a stable or decreasing dose of ≤ 10 mg daily (or equivalent)
             for at least 7 days prior to first study treatment. Treatment for brain metastases may
             include whole brain radiotherapy, radiosurgery, or a combination as deemed appropriate
             by the treating physician. Participants with CNS metastases treated by neurosurgical
             resection or brain biopsy performed within 28 days before study treatment initiation
             will be excluded.

          -  The subject has uncontrolled, significant intercurrent or recent illness. Individuals
             with a history of different malignancy are ineligible except for the following
             circumstances. Individuals with a history of other malignancies are eligible if they
             have been disease-free for at least 3 years or are deemed by the investigator to be at
             low risk for recurrence of that malignancy.

          -  Participant has an active infection requiring IV antibiotics at initiation of study
             therapy.

          -  Patient has a medical condition that requires chronic systemic steroid therapy or on
             any other form of immunosuppressive medication. For example, participants with
             autoimmune disease that requires systemic steroids or immunosuppression agents should
             be excluded. Replacement therapy (eg., thyroxine, insulin, or physiologic
             corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is
             not considered a form of systemic treatment.

          -  Subjects with current pneumonitis, or requiring supplementary O2 therapy.

          -  The participant is known to be positive for human immunodeficiency virus (HIV),
             HepBsAg, or HCV RNA. HIV-positive participants on combination antiretroviral therapy
             are ineligible

          -  Participants with any other active malignancy requiring concurrent intervention.

          -  Known hypersensitivity to any of the components of ipilimumab or nivolumab.

          -  The participant has received a live vaccine within 28 days prior to the first dose of
             trial treatment and while participating in the trial. Examples of live vaccines
             include, but are not limited to, the following: measles, mumps, rubella,
             varicella/zoster, yellow fever, rabies, BCG, and typhoid vaccine. The use of the
             inactivated seasonal influenza vaccine (Fluzone®) is allowed.

          -  The participant is pregnant or breastfeeding.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Response Rate of nivolumab in combination with ipilimumab
Time Frame:2 years
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Overall Response Rate of the combination according to immune-related response criteria
Time Frame:2 years
Safety Issue:
Description:
Measure:Clinical Benefit Rate
Time Frame:2 Years
Safety Issue:
Description:
Measure:Progression Free Survival
Time Frame:2 years
Safety Issue:
Description:
Measure:Overall Survival
Time Frame:2 years
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Dana-Farber Cancer Institute

Trial Keywords

  • Breast Cancer

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