Carboplatin +/- Nivolumab in Metastatic Triple Negative Breast Cancer

NCT03414684 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 2 other identifiers: 17-512CA209-9JX
• Study Type: interventional
• Target: 78
• Locations: 1 country
• Sites: 10

Brief Summary

This research study is studying a drug called Carboplatin with or without another study drug, Nivolumab as a possible treatment for triple-negative breast cancer that has spread to other parts of the body. The interventions involved in this study are:

• Carboplatin
• Nivolumab

Conditions

Breast Cancer

Keywords

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival

  Defined as the time from randomization to the earlier of progression or death due to any cause. Participants alive without disease progression are censored at date of last disease evaluation

  Assessed from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, up to 3.5 years

Secondary Outcomes (27)

• Objective Response Rate by Response Evaluation Criteria in Solid Tumours (RECIST) 1.1

  Assessed from the start of treatment until disease progression, complete response (after at least 24 weeks of treatment), intercurrent illness, unacceptable toxicity, noncompliance/withdrawal, or general/specific worsening of condition, up to 3.5 years

• Objective Response Rate by Immune-Related Response Criteria (irRC)

  Assessed from the start of treatment until disease progression, complete response (after at least 24 weeks of treatment), intercurrent illness, unacceptable toxicity, noncompliance/withdrawal, or general/specific worsening of condition, up to 3.5 years

• Overall Survival

  Assessed from date of randomization until the date of death from any cause, up to 3.5 years

• Clinical Benefit Rate

  Assessed from the start of treatment until disease progression, complete response (after at least 24 weeks of treatment), intercurrent illness, unacceptable toxicity, noncompliance/withdrawal, or general/specific worsening of condition, up to 3.5 years

• Duration of Response

  Assessed from the time measurement criteria are met for CR or PR by RECIST 1.1 (whichever is first recorded) to the time of first progression, up to 2.75 years

Study Arms (2)

Carboplatin + Nivolumab

EXPERIMENTAL

* Nivolumab is administered every three weeks intravenously * Nivolumab dosage is 360mg * Carboplatin is administered every three weeks intravenously * Carboplatin dosage is pre-determined by the PI

Drug: Carboplatin; Drug: Nivolumab

Carboplatin

ACTIVE COMPARATOR

* Carboplatin is administered every three weeks intravenously * Carboplatin dosage is pre-determined by the PI

Drug: Carboplatin

Interventions

Carboplatin DRUG

Carboplatin interferes with the development of the genetic material in a cell, which will cause the cancer cells to die.

Carboplatin; Carboplatin + Nivolumab

Nivolumab DRUG

Nivolumab works by attaching to and blocking a molecule called PD-1. PD-1 is a different molecule that can turn off the immune system by interacting with PD-L1 on the cancer cells

Also known as: Opdivo

Carboplatin + Nivolumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must have histologically or cytologically confirmed invasive breast cancer, with unresectable locally advanced or metastatic disease. Participants without pathologic or cytologic confirmation of metastatic disease should have unequivocal evidence of metastasis from physical examination or radiologic evaluation.
• Participants must have PD-L1 status available at the time of registration. Standard local testing with any PD-L1 antibody that has been validated in a CLIA-certified environment will be acceptable for including patients on trial.. Primary or metastatic samples may be tested for PD-L1 status.
• Participants must have measurable or evaluable disease by RECIST version 1.1.
• Participants must agree to undergo a research biopsy, if tumor is safely accessible, at baseline. Previously collected archival tissue will also be obtained on all participants. For participants for whom newly-obtained samples cannot be provided (e.g. inaccessible or participant safety concern) the archival tissue alone will be acceptable. Tissue needs to be located and availability confirmed at time of registration (See Section 9 for more details). Participants must agree to a mandatory repeat biopsy 3-6 weeks after starting treatment, if tumor is safely accessible. For patients randomized to carboplatin alone who decide to crossover to nivolumab and nab-paclitaxel at time of progression, a mandatory biopsy will be required if tumor is safely accessible prior to initiating crossover treatment; participants must also agree to undergo this biopsy, if applicable.
• Prior chemotherapy: Participants must have received 0 prior chemotherapeutic regimens for metastatic breast cancer. Prior platinum in the neo/adjuvant setting is permissible, if at least 6 months elapsed since the end of adjuvant systemic therapy to the development of metastatic disease. All toxicities related to prior chemotherapy must have resolved to CTCAE v4.0 grade 1 or lower, unless otherwise specified.
• Prior biologic therapy: Prior poly-ADP ribose polymerase (PARP) inhibitors are not allowed in the metastatic setting. Prior PARP inhibitors in the neo/adjuvant setting are permissible, if at least 6 months elapsed since the end of adjuvant systemic therapy to the development of metastatic disease. All toxicities related to prior biologic therapy must have resolved to CTCAE v4.0 grade 1 or lower, unless otherwise specified.
• Prior radiation therapy: Patients may have received prior radiation therapy. Radiation therapy must be completed at least 14 days prior to registration, and all toxicities related to prior radiation therapy must have resolved to CTCAE v4.0 grade 1 or lower, unless otherwise specified in 3.1.10. Patients may not have had \>25% of their bone marrow radiated.
• The subject is ≥18 years old.
• ECOG performance status ≤1 (Karnofsky \>60%, see Appendix A).
• Participants must have normal organ and marrow function as defined below:
• Absolute neutrophil count ≥1,500/mcL
• Platelets ≥100,000/mcL
• Hemoglobin ≥ 9.0 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

You may not qualify if:

• Concurrent administration of any other anti-cancer therapy during the course of this study (bisphosphonates and RANK ligand inhibitors are allowed).
• Prior hypersensitivity to platinum chemotherapy or to any of the excipients of platinum or nivolumab therapy.
• Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including pembrolizumab, ipilimumab, and any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
• 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 without ongoing requirement for corticosteroids, as ascertained by clinical examination and brain imaging (magnetic resonance imaging or CT scan) completed during screening. Any corticosteroid use for brain metastases must have been discontinued without the subsequent appearance of symptoms for ≥7 days prior to registration. Treatment for brain metastases may include whole brain radiotherapy, radiosurgery, surgery or a combination as deemed appropriate by the treating physician. Radiation therapy must be completed at least 7 days prior to registration
• Major surgery within 2 weeks prior to registration. Patients must have recovered from any effects of any major surgery.
• Uncontrolled, significant intercurrent or recent illness including, but not limited to, ongoing or active infection, uncontrolled non-malignant systemic disease, uncontrolled seizures, or psychiatric illness/social situation that would limit compliance with study requirements in the opinion of the treating investigator.
• Participant has a medical condition that requires chronic systemic steroid therapy (\> 10 mg of prednisone daily or equivalent) or any other form of immunosuppressive medication (including disease modifying agents) and has required such therapy in the last 2 years. Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic therapy.
• Participant has documented history of autoimmune disease or syndrome that currently requires systemic steroids or immunosuppressive agents.
• History or evidence of active, non-infectious pneumonitis or interstitial lung disease.
• Individuals with a history of a second 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. Individuals with the following cancers that have been diagnosed and treated within the past 3 years are eligible: cervical/prostate carcinoma in situ, superficial bladder cancer, non-melanoma cancer of the skin. Patients with other cancers diagnosed within the past 3 years and felt to be at low risk of recurrence should be discussed with the study sponsor to determine eligibility.
• Participant is known to be positive for the human immunodeficiency virus (HIV), HepBsAg, or HCV RNA. HIV-positive participants are ineligible because of the potential for pharmacokinetic interactions of combination antiretroviral therapy with study drugs. In addition, these participants are at increased risk of fatal infections when treated with marrow-suppressive therapy.
• The participant has received a live vaccine within 28 days prior to registration. 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 is allowed.
• Women who are pregnant or breastfeeding or adults of reproductive potential not employing an adequate method of contraception.
• 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 have not undergone surgical sterilization (removal of ovaries and/or uterus)

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Bristol-Myers Squibb: collaborator

Study Sites (10)

The Stamford Hospital

Stamford, Connecticut, 06904, United States

Location

Eastern Maine Medical Center

Bangor, Maine, 04401, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02115, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

St. Elizabeth's Medical Center

Boston, Massachusetts, 02135, United States

Location

Dana-Farber/Brigham and Women's Cancer Center at Milford Regional Medical Center

Milford, Massachusetts, 01757, United States

Location

Dana-Farber/Brigham and Women's Cancer Center in clinical affiliation with South Shore Hospital

South Weymouth, Massachusetts, 02190, United States

Location

Dana-Farber/New Hampshire Oncology-Hematology

Londonderry, New Hampshire, 03053, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

University of Vermont Medical Center

Burlington, Vermont, 05401, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Carboplatin; Nivolumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Sara Tolaney, MD, MPH
• Organization: Dana-Farber Cancer Institute

Sara_Tolaney@dfci.harvard.edu

617-632-5743

Study Officials

• Sara Tolaney, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 1, 2017
• First Posted: January 30, 2018
• Study Start: January 30, 2018
• Primary Completion: September 28, 2021
• Study Completion (Estimated): July 30, 2026
• Last Updated: September 29, 2025
• Results First Posted: January 26, 2023

Record last verified: 2025-09

Locations

US (10)