Overview

Carboplatin +/- Nivolumab in Metastatic Triple Negative Breast Cancer

Status:
Active, not recruiting
Trial end date:
2025-06-30
Target enrollment:
0
Participant gender:
All
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
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Dana-Farber Cancer Institute
Collaborator:
Bristol-Myers Squibb
Treatments:
Antibodies, Monoclonal
Carboplatin
Nivolumab
Criteria
Inclusion Criteria:

- 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.

- Estrogen-receptor and progesterone-receptor expression both ≤ 1% by
immunohistochemistry (IHC), and HER2-negative status as determined by the current
ASCO/CAP guidelines. If a patient has more than one histological result, the most
recent sample will be considered for inclusion.

- 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

≤5 × institutional ULN for participants with documented liver metastases

- Serum creatinine ≤1.5 × institutional ULN OR creatinine clearance ≥ 45 mL/min/
1.73m2 for participants with creatinine levels above institutional ULN.

- Supportive care (e.g. transfusion of red blood cells) is allowed to meet eligibility
criteria.

- Female subjects of childbearing potential must have a negative serum or urine
pregnancy test within 2 weeks prior to registration.

- 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).

- Women of childbearing potential (WOCBP) must agree to use an adequate method of
contraception. Contraception is required starting with the first dose of study
medication through 150 days (5 months) after the last dose of study medication.
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. Periodic abstinence (e.g., calendar, ovulation,
symptothermal, or postovulation methods) and withdrawal are not acceptable methods of
contraception.

- Males who are sexually active with WOCBP must agree to follow instructions for
method(s) of contraception for the duration of study treatment with nivolumab and 7
months after the last dose of study treatment (i.e., 90 days (duration of sperm
turnover) plus the time required for the investigational drug to undergo approximately
five half-lives.)

- Participants on bisphosphonates or RANK ligand inhibitors may continue receiving
therapy during study treatment.

- The participant must be capable of understanding and complying with the protocol and
willing to sign a written informed consent document

Exclusion Criteria:

- 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)