Cabozantinib +/- Trastuzumab In Breast Cancer Patients w/ Brain Metastases

NCT02260531 | Completed Phase 2 Results DMC

• 1 other identifier: 14-359
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 2

Brief Summary

This research study is evaluating the effectiveness of the drug called cabozantinib (alone or in combination with trastuzumab) as a possible treatment for advanced breast cancer in which the cancer has spread to the brain.

Conditions

Breast Cancer; Brain Tumor - Metastatic

Keywords

Metastatic breast cancer and brain metastases; HER-2 Positive Breast Cancer; ER-Positive PR-Positive HER-2 Negative Breast Cancer; ER-Negative PR-Negative HER2-Negative Breast Cancer

Outcome Measures

Primary Outcomes (1)

• CNS Objective Response Rate (ORR)

  The central nervous system (CNS) ORR was defined as the percentage of participants achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria in the evaluation CNS lesions on treatment: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.

  Disease assessments occurred every 6 cycles. Patients with stable or responsive disease after completion of 6 cycles could reduce frequency of assessments to every 3 cycles. Response was evaluated up to 25 months.

Secondary Outcomes (7)

• CNS Volumetric Objective Response Rate (ORR)

  Disease assessments occurred every 6 cycles. Patients with stable or responsive disease after completion of 6 cycles could reduce frequency of assessments to every 3 cycles. Response was evaluated up to 25 months .

• Non-CNS Objective Response Rate (ORR)

  Disease assessments occurred every 6 cycles. Patients with stable or responsive disease after completion of 6 cycles could reduce frequency of assessments to every 3 cycles. Response was evaluated up to 25 months.

• Median Progression-Free Survival (PFS)

  Disease assessments occurred every 6 cycles. Patients with stable or responsive disease after completion could reduce frequency to every 3 cycles. In long-term follow-up, assessments occurred every 6 months until death. Follow-up time is up to 25 months.

• 12-Week Clinical Benefit Rate

  Evaluate at 12 weeks.

• First Progression Site

  Disease assessments occurred every 6 cycles. Patients with stable or responsive disease after completion could reduce frequency to every 3 cycles. In long-term follow-up, assessments occurred every 6 months until death. Follow-up time is up to 25 months.

Study Arms (3)

Cohort 1 - Cabozantinib, Trastuzumab for HER2+

EXPERIMENTAL

HER2-positive * Cabozantinib- orally administered daily per treatment cycle, 60 mg per day * Trastuzumab- IV administered once per cycle, 8 mg/kg IV loading dose followed by 6 mg/kg IV Cycle duration equals 3 weeks. Patients are treated indefinitely based on unacceptable toxicity, disease progression, or withdrawal for other reasons.

Drug: Cabozantinib; Drug: Trastuzumab

Cohort 2 - Cabozantinib for ER+ and/or PR+

EXPERIMENTAL

Hormone receptor-positive (ER+ and/or PR+) \- Cabozantinib- orally administered daily per treatment cycle, 60 mg per day Cycle duration equals 3 weeks. Patients are treated indefinitely based on unacceptable toxicity, disease progression, or withdrawal for other reasons.

Drug: Cabozantinib

Cohort 3 - Cabozantinib for ER-, PR-, HER2-

EXPERIMENTAL

Triple negative (ER-, PR-, HER2-) \- Cabozantinib- orally administered daily per treatment cycle, 60 mg per day Cycle duration equals 3 weeks. Patients are treated indefinitely based on unacceptable toxicity, disease progression, or withdrawal for other reasons.

Drug: Cabozantinib

Interventions

Cabozantinib DRUG

Also known as: Cometriq®

Cohort 1 - Cabozantinib, Trastuzumab for HER2+; Cohort 2 - Cabozantinib for ER+ and/or PR+; Cohort 3 - Cabozantinib for ER-, PR-, HER2-

Trastuzumab DRUG

Also known as: Herceptin

Cohort 1 - Cabozantinib, Trastuzumab for HER2+

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically or cytologically confirmed invasive breast cancer, with stage IV disease.
• New or progressive CNS lesions, as assessed by the patient's treating physician.
• For patients who have received prior cranial radiation, no increase in corticosteroid dose in the week prior to the baseline brain MRI
• Discontinued prior therapy (with the exception of trastuzumab for patients with HER2+ breast cancer)
• Recovery to baseline or ≤ Grade 1 CTCAE v.4.0 from toxicities related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy;
• The subject has an ECOG performance status of 0 or 1
• Patients must have normal organ and marrow function and laboratory values as follows within 14 days before the first dose of cabozantinib
• Sexually active subjects (men and women) must agree to use medically accepted barrier methods of contraception (e.g., male or female condom) during the course of the study and for 4 months after the last dose of study drug(s)
• Subjects of childbearing potential must not be pregnant at screening.
• Patients on bisphosphonates may continue receiving bisphosphonate therapy during study. Patients wanting to initiate bisphosphonate therapy may do so.
• The subject has had an assessment of all known disease sites eg, by computerized tomography (CT) scan, magnetic resonance imaging (MRI), bone scan as appropriate, within 28 days before the first dose of cabozantinib

You may not qualify if:

• The subject has received cabozantinib or another c-Met inhibitor (please note ARQ 197 is not considered a MET inhibitor for purposes of this study given data to suggest it inhibits tubulin)
• The subject has uncontrolled, significant intercurrent or recent illness
• Leptomeningeal disease as the only site of CNS involvement
• Known contraindication to MRI with gadolinium contrast, such as cardiac pacemaker, shrapnel, or ocular foreign body
• More than 2 seizures over the last 4 weeks prior to study entry
• Grade 1 or higher CNS hemorrhage on baseline brain MRI, or history of grade 2 or higher CNS hemorrhage within 12 months
• Has experienced clinically-significant GI bleeding within 6 months before first dose of cabozantinib; hemoptysis of ≥ 0.5 teaspoon (2.5ml) of red blood within 3 months before the first dose of cabozantinib; any other signs indicative of pulmonary hemorrhage within 3 months before the first dose of cabozantinib
• The subject has tumor in contact with, invading or encasing any major blood vessels
• The subject has 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
• The subject requires concomitant treatment, in therapeutic doses, with anticoagulants. Low dose aspirin (≤ 81 mg/day), low-dose warfarin ( ≤1 mg/day), and prophylactic LMWH are permitted.
• The subject has prothrombin time (PT)/INR or partial thromboplastin time (PTT) test ≥1.3 × the laboratory ULN within 7 days before the first dose of cabozantinib.
• Inability to swallow intact tablets
• Pregnant or lactating females
• Diagnosis of another malignancy within 2 years before the first dose of cabozantinib, except for superficial skin cancers, or localized, low grade tumors deemed cured and not treated with systemic therapy
• Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Exelixis: collaborator
• Genentech, Inc.: collaborator

Study Sites (2)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Related Publications (1)

• Leone JP, Duda DG, Hu J, Barry WT, Trippa L, Gerstner ER, Jain RK, Tan S, Lawler E, Winer EP, Lin NU, Tolaney SM. A phase II study of cabozantinib alone or in combination with trastuzumab in breast cancer patients with brain metastases. Breast Cancer Res Treat. 2020 Jan;179(1):113-123. doi: 10.1007/s10549-019-05445-z. Epub 2019 Sep 20.

  PMID: 31541381 DERIVED

MeSH Terms

Conditions

Breast Neoplasms; Brain Neoplasms; Triple Negative Breast Neoplasms

Interventions

cabozantinib; Trastuzumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

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

617-632-3800

Study Officials

• Sara Tolaney, MD, MPH

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: September 17, 2014
• First Posted: October 9, 2014
• Study Start: November 1, 2014
• Primary Completion: January 4, 2019
• Study Completion: March 17, 2020
• Last Updated: May 20, 2021
• Results First Posted: May 18, 2021

Record last verified: 2021-05

Locations

US (2)