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

This study is currently recruiting participants.
See Contacts and Locations
Verified January 2017 by Sara Tolaney, Dana-Farber Cancer Institute
Sponsor:
Collaborators:
Exelixis
Genentech, Inc.
Information provided by (Responsible Party):
Sara Tolaney, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT02260531
First received: September 17, 2014
Last updated: January 23, 2017
Last verified: January 2017
  Purpose
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.

Condition Intervention Phase
Breast Cancer Brain Tumor - Metastatic Drug: Cabozantinib Drug: Trastuzumab Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: A Phase II Study of Cabozantinib Alone or in Combination With Trastuzumab in Breast Cancer Patients With Brain Metastases

Resource links provided by NLM:


Further study details as provided by Sara Tolaney, Dana-Farber Cancer Institute:

Primary Outcome Measures:
  • CNS Objective Response Rate [ Time Frame: 2 Years ]
    HER2-positive metastatic breast cancer and brain metastases RECIST 1.1


Secondary Outcome Measures:
  • CNS Objective Response Rate [ Time Frame: 2 Years ]
    CNS Objective Response Rate hormone receptor positive metastatic breast cancer and brain metastases RECIST 1.1

  • CNS Objective Response Rate [ Time Frame: 2 Years ]
    CNS ORR in patients with triple-negative metastatic breast cancer and brain metastases RECIST 1.1

  • CNS Objective Response Rate [ Time Frame: 2 Years ]
    CNS ORR in patients with HER2-positive, hormone receptor positive, and triple-negative metastatic breast cancer and brain metastases by volumetric criteria and composite criteria

  • ORR in non-CNS [ Time Frame: 2 Years ]
    To evaluate ORR in non-CNS sites (by RECIST 1.1)

  • Progression Free Survival Rate [ Time Frame: 2 Years ]
  • Clinical benefit rate [ Time Frame: 2 Years ]
  • First Progression Rate (CNS versus non-CNS) [ Time Frame: 2 Years ]
  • Overall Survival (OS) Rate [ Time Frame: 2 Years ]
  • Participants will be grouped as to whether or not their tumor has amplified Met [ Time Frame: Baseline ]
  • To evaluate the incidence of c-Met amplified circulating tumor cells at baseline [ Time Frame: Baseline ]
  • To evaluate potential plasma biomarkers of cabozantinib when given in combination with trastuzumab [ Time Frame: 2 Years ]
  • To assess vascularity of CNS tumors, through descriptive analysis as a composite of tumor vessel size, cerebral blood volume, cerebral blood flow, perfusion, and diffusion before and after exposure to cabozantinib by research MRIs [ Time Frame: 2 Years ]
  • To assess the number of participants with Adverse Events [ Time Frame: 2 Years ]

Estimated Enrollment: 40
Study Start Date: October 2014
Estimated Study Completion Date: February 2022
Estimated Primary Completion Date: June 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ARM 1

HER2-positive

  • Cabozantinib- orally administered daily per treatment cycle
  • Trastuzumab- IV administered once per cycle
  • MRI- Baseline, Cycle 2 Day 1, and every 2 cycles
  • Magnetic Resonance Angiography (MRA ), Baseline, Cycle 2 Day 1,
Drug: Cabozantinib
One, 60 mg tablet daily of each 21 day cycle. Number of Cycles: until progression or unacceptable toxicity develops.
Other Name: Cometriq®
Drug: Trastuzumab
For HER2-Positive participants only. Administered by IV on day 1 of each 21 day cycle. Number of Cycles: until progression or unacceptable toxicity develops.
Other Name: Herceptin
Experimental: ARM 2

Hormone receptor-positive (ER+ and/or PR+)

  • Cabozantinib- orally administered daily per treatment cycle
  • MRI- Baseline, Cycle 2 Day 1, and every 2 cycles
  • Magnetic Resonance Angiography (MRA ), Baseline, Cycle 2 Day 1,
Drug: Cabozantinib
One, 60 mg tablet daily of each 21 day cycle. Number of Cycles: until progression or unacceptable toxicity develops.
Other Name: Cometriq®
Experimental: ARM 3

Triple negative (ER-, PR-, HER2-)

  • Cabozantinib- orally administered daily per treatment cycle
  • MRI- Baseline, Cycle 2 Day 1, and every 2 cycles
  • Magnetic Resonance Angiography (MRA ), Baseline, Cycle 2 Day 1,
Drug: Cabozantinib
One, 60 mg tablet daily of each 21 day cycle. Number of Cycles: until progression or unacceptable toxicity develops.
Other Name: Cometriq®

Detailed Description:

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

The FDA (the U.S. Food and Drug Administration) has not approved cabozantinib for your specific disease but it has been approved for other uses.

Few treatments exist for brain metastases from breast cancer. Radiation and surgery are generally included as a possible standard of care treatments for this diagnosis.

In this research study, the investigator are looking at how well cabozantinib works in treating breast cancer that has spread to the brain. Cabozantinib has been used in some phase I studies and information from those other research studies suggests that cabozantinib may help to shrink or stabilize the participant's breast cancer. In addition, information from these studies has shown that cabozantinib may pass through the blood brain barrier (a protective layer that prevents most large molecules and cells found in the blood from entering the brain tissue) and may be an effective treatment for brain metastases.

If the participant has HER2-positive breast cancer, they will receive trastuzumab in addition to cabozantinib. Trastuzumab is an FDA approved drug for the treatment of HER2-positive metastatic breast cancer. However, the combination of cabozantinib and trastuzumab has not yet been tested. Trastuzumab may help to shrink or stabilize breast cancer in combination with cabozantinib. If the participant's breast cancer is HER2-negative, they will not receive trastuzumab as part of this clinical trial.

The names of the study interventions involved in this study are:

  • Cabozantinib (XL184)
  • Trastuzumab (herceptin) (participants with HER2-positive disease only)
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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 4 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

Exclusion Criteria:

  • 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
  • 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
  • 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
  • The subject is known to be positive for the human immunodeficiency virus (HIV)
  • Subjects with clinically relevant ongoing complications from prior surgery are not eligible
  • QTcF > 500 msec on average of screening EKGs performed within 28 days of first dose of cabozantinib. Three EKGs must be performed at screening. If the average of these three consecutive results for QTcF is > 500 msec, the subject is ineligible.
  • Active infection requiring IV antibiotics at Day 1 of cycle 1
  • No prior lapatinib within 7 days prior to initiation of protocol treatment
  • Previously identified allergy or hypersensitivity to components of the cabozantinib formulations
  • The subject requires chronic concomitant treatment with strong CYP3A4 inducers
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02260531

Contacts
Contact: Sara Tolaney, MD, MPH 617-632-5743 STOLANEY@PARTNERS.ORG

Locations
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Steven Isakoff, MD, PhD    617-726-4920    sisakoff@partners.org   
Principal Investigator: Steven Isakoff, MD, PhD         
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Sara Tolaney, MD    617-632-3800    stolaney@partners.org   
Principal Investigator: Sara Tolaney, MD         
Sponsors and Collaborators
Dana-Farber Cancer Institute
Exelixis
Genentech, Inc.
Investigators
Principal Investigator: Sara Tolaney, MD, MPH Dana-Farber Cancer Institute
  More Information

Responsible Party: Sara Tolaney, Principal Investigator, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT02260531     History of Changes
Other Study ID Numbers: 14-359
Study First Received: September 17, 2014
Last Updated: January 23, 2017

Keywords provided by Sara Tolaney, Dana-Farber Cancer Institute:
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

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasm Metastasis
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Neoplastic Processes
Pathologic Processes
Trastuzumab
Antineoplastic Agents

ClinicalTrials.gov processed this record on July 26, 2017