A Phase II Study of Nivolumab in Combination With Cabozantinib for Metastatic Triple-negative Breast Cancer

NCT03316586 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 17-324
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

This research study is studying a combination of drugs as a possible treatment for metastatic triple-negative breast cancer. The drugs involved in this study are:

• Cabozantinib (XL184)
• Nivolumab

Conditions

Breast Cancer

Keywords

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate

  Overall response rate (ORR) is defined as the percentage of patients with complete or partial response evaluated by RECIST 1.1. Per RECIST 1.1: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

  2 years

Secondary Outcomes (4)

• Number of Participants With Adverse Events

  2 years

• Clinical Benefit Rate

  2 years

• Progression Free Survival Rate

  5 years

• Overall Response Rate Per Immune Criteria

  2 years

Study Arms (1)

Nivolumab + Cabozantinib

EXPERIMENTAL

* Nivolumab was administered every 28 days at a dose of 480mg given intravenously over 30 minutes (+/- 10 minutes) using a volumetric pump with 0.2 to 1.2 micron pore size, low protein binding polyethersulfone membrane in-line filter * Cabozantinib was administered orally, once daily for 28 days at a dose of 40 mg.

Drug: Nivolumab; Drug: Cabozantinib

Interventions

Nivolumab DRUG

Nivolumab is an experimental antibody drug that may make the immune response more active against cancer.

Also known as: Opdivo

Nivolumab + Cabozantinib

Cabozantinib DRUG

Cabozantinib may help to shrink or stabilize breast cancer

Also known as: Cabometyx

Nivolumab + Cabozantinib

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• 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 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 measurable disease by RECIST version 1.1
• Participants must agree to undergo a research biopsy, if tumor is safely accessible, at baseline and 7-14 days prior to Cycle 3 Day 1. Participants for whom newly-obtained samples cannot be provided (e.g. inaccessible or participant safety concern) may submit an archived specimen.
• Note: After the first 6 participants undergo biopsy on cabozantinib, we will review their adverse event profiles to ensure no more than a 20% rate of grade 3 or higher bleeding or wound healing complications occur. If more than 2 patients (\>20%) have safety concerns, we will reassess the safety of collecting the research biopsies. Full review of all grade (including grade 1 and 2) may also prompt changes and will be reviewed by the study team. Exelixis may be consulted if necessary.
• 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 registration. Participants should also be adequately recovered from acute toxicities of prior treatment.
• Prior biologic therapy: Patients must have discontinued all biologic therapy at least 14 days prior to registration.
• Prior radiation therapy: Patients may have received prior radiation therapy in either the metastatic or early-stage setting. Radiation therapy must be completed per the following timelines:
• Radiotherapy to the thoracic cavity or abdomen within 4 weeks prior to registration.
• Radiotherapy to bone lesions within 2 weeks prior to registration.
• Radiotherapy to any other site within 4 weeks prior to registration.
• In all cases, there must be complete recovery and no ongoing complications from prior radiotherapy.
• The subject is ≥18 years old.
• ECOG (Eastern Cooperative Oncology Group) performance status ≤1(Karnofsky ≥60%, see Appendix A)
• Participants must have normal organ and marrow function as defined below:
• absolute neutrophil count ≥1,000/microliter (mcL)

You may not qualify if:

• Major surgery within 12 weeks before the first dose of study treatment. Complete wound healing from major surgery must have occurred 1 month before the first dose of study treatment. Minor surgery (including uncomplicated tooth extractions) within 28 days before the first dose of study treatment with complete wound healing at least 10 days before the first dose of study treatment. No clinically relevant ongoing complications from prior surgery are not eligible.
• The participant has tumor in contact with, invading, or encasing major blood vessels or radiographic evidence of significant cavitary pulmonary lesions.
• The subject has pathologic evidence of tumor invading the GI tract (esophagus, stomach, small or large bowel, rectum or anus), or any evidence of endotracheal or endobronchial tumor within 28 days before the first dose of cabozantinib;
• 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.
• The participant has received a prior c-Met inhibitor
• Has received prior therapy with an anti-programmed cell death-1 (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 having no evidence of progression for ≥ 1 month 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. Any corticosteroid use for brain metastases must have been discontinued without the subsequent appearance of symptoms for ≥2 weeks prior to registration. 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 2 months before day 1 will be excluded.
• The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
• Cardiovascular disorders including:
• Congestive heart failure (CHF): New York Heart Association (NYHA) Class III (moderate) or Class IV (severe) at the time of screening;
• Concurrent uncontrolled hypertension defined as sustained blood pressure (BP) \> 150 mm Hg systolic or \> 100 mm Hg diastolic despite optimal antihypertensive treatment within 7 days of the first dose of study treatment;
• Any history of congenital long QT syndrome;
• Any of the following within 6 months before the first dose of study treatment:
• unstable angina pectoris;

Sponsors & Collaborators

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

Study Sites (1)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Nivolumab; cabozantinib

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

Only one of the first 18 patients had a PR. The study therefore did not meet the prespecified criteria to proceed to the second stage of the trial, and it was closed to further accrual.

Results Point of Contact

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

Sara_Tolaney@dfci.harvard.edu

617-632-2335

Study Officials

• Sara Tolaney, MD, MPH

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: October 18, 2017
• First Posted: October 20, 2017
• Study Start: November 30, 2017
• Primary Completion: August 30, 2019
• Study Completion: August 30, 2019
• Last Updated: December 28, 2021
• Results First Posted: December 28, 2021

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)