Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Cabozantinib for Metastatic Triple Negative BrCa

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Sara Tolaney, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT01738438
First received: November 28, 2012
Last updated: July 7, 2014
Last verified: July 2014
  Purpose

This research study is Phase II clinical trial, which tests the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific cancer. "Investigational" means that the drug is being studied. It also means that the FDA has not yet approved XL184 for use in patients, including people with your type of cancer.

XL184 is a drug that may stop cancer cells from growing. It is a small molecule kinase inhibitor that inhibitors met and VEGFR2, as well as other targets. This drug has been used in Phase I studies in humans and laboratory experiments, and information from those other research studies suggests that this drug may help to slow tumor progression in this research study. This drug has also been used in a phase II study for breast cancer patients (a randomized discontinuation trial) suggesting good benefit for this group of patients.

In this research study, we are looking at the anti-tumor effects of XL184 in metastatic breast cancer.


Condition Intervention Phase
Breast Cancer
Drug: XL184
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of XL184 (Cabozantinib) for Metastatic Triple-Negative Breast Cancer

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Evaluation of XL184 based on objective response rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To evaluate the activity of XL184, as defined by objective response rate (ORR) in patients with triple-negative metastatic breast cancer


Secondary Outcome Measures:
  • Progression Free Survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Evaluation of Progression Free Survival

  • c-Met and phospho c-Met expression [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To evaluate c-Met and phospho c-Met expression in archival tumor tissue

  • Incidence of c-Met amplified circulating tumor cells [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To evaluate the incidence of c-Met amplified circulating tumor cells at baseline

  • Evaluation of potential serum biomarkers [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Evaluate potential serum biomarkers of XL184

  • Evaluate PTEN loss and PI3K mutations [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To evaluate PTEN loss and PI3K mutations in archival tumor tissue

  • Evaluate change in radiotracer uptake within tumor site [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Evaluate if the percent change in radiotracer uptake within the tumor site(s) from baseline to the first and second follow-up FDG-PET/CT correlates RECIST response


Estimated Enrollment: 35
Study Start Date: February 2013
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Experimental Treatment Arm
XL184, taken orally once per day
Drug: XL184
Other Name: Cabozantinib

Detailed Description:

In order to determine if you are eligible to participate in this study you will need to undergo some tests and procedures. Many of these tests and procedures are likely to be part of regular cancer care and may be done even if it turns out that you do not take part in the research study. If you have had some of these tests and procedures recently, they may or may not have to be repeated. These tests and procedures include a medical history, physical exam, performance status, assessment of your tumor, blood tests, a urine test and a pregnancy test (if applicable). If these tests show that you are eligible to participate in the research study, you will begin the study treatment. If you do not meet the eligibility criteria, you will not be able to participate in this research study.

If you take part in this research study, you will be given a one month supply of XL184 and a study drug-dosing calendar for each treatment cycle. Each treatment cycle lasts 3 weeks during which time you will be taking the study drug once per day by mouth.

During all cycles you will have a physical exam and you will be asked questions about your general health and specific questions about any problems that you might be having and any medications you may be taking.

The investigators will assess your tumor by CT scan or MRI after 6 weeks of treatment, and then every nine weeks you remain on treatment.

The investigators will try to obtain samples of your tumor tissue from a biopsy if you have had one previously. A new biopsy is optional, but may provide researchers with additional information about how XL184 affects the tumor cells.

Participants will receive a pain questionnaire along with information on how to fill in the questionnaire.

The investigators would like to keep track of your medical condition for the rest of your life. The investigators would like to do this by calling you on the telephone once every 6 months to see how you are doing. Keeping in touch with you and checking your condition every year helps us look at the long-term effects of the research study.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically or cytologically confirmed invasive breast cancer with stage IV disease
  • Primary tumor and/or metastasis must be ER-negative, PR-negative and HER2-negative
  • May have received 0-3 prior chemotherapeutic regimens for metastatic breast cancer. Must be off treatment for at least 21 days prior to enrollment
  • Must have discontinued all biologic therapy at least 14 days before enrollment
  • May have received prior radiation therapy in the early stage or metastatic setting, but must have completed treatment at least 14 days prior to enrollment
  • Must agree to use medically acceptable methods of contraception
  • Confirmed availability of formalin-fixed, paraffin-embedded tumor tissue
  • Able to swallow tablets

Exclusion Criteria:

  • Pregnant or breastfeeding
  • Received another investigational agent within 14 days prior to enrollment
  • Received prior c-Met inhibitor
  • Known brain metastases that are untreated, symptomatic or require therapy to control symptoms
  • Psychiatric illness or social situation that could limit ability to comply with study requirements
  • Require concomitant treatment in therapeutic doses with anticoagulants or antiplatelet agents
  • Diagnosis of another malignancy requiring systemic treatment within the last two years (except non-melanoma skin cancer or in-situ carcinoma of the cervix)
  • Known to be positive for HIV
  • Active infection requiring IV antibiotics at Day 1 of cycle 1
  • Uncontrolled, significant intercurrent illness
  • Requires chronic concomitant treatment of a strong CYP3A4 inducer
  • tumor in contact with, invading or encasing major blood vessels
  • Have experienced clinically significant gastrointestinal bleeding within 6 months, hemoptysis of more than 0.5 teaspoon of red blood within 3 months or other signs indicative of pulmonary hemorrhage within 3 months of enrollment
  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: NCT01738438

Locations
United States, Massachusetts
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02215
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02215
Dana-Farber Cancer Institute at Faulkner Hospital
Boston, Massachusetts, United States, 02130
Massachusetts General Hospital
Boston, Massachusetts, United States, 02214
Sponsors and Collaborators
Dana-Farber Cancer Institute
Investigators
Principal Investigator: Sara Tolaney, MD, MPH Dana-Farber Cancer Institute
  More Information

No publications provided

Responsible Party: Sara Tolaney, Prinicipal Investigator, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT01738438     History of Changes
Other Study ID Numbers: 12-431
Study First Received: November 28, 2012
Last Updated: July 7, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Dana-Farber Cancer Institute:
Metastatic
Triple Negative
Stage IV

Additional relevant MeSH terms:
Breast Neoplasms
Triple Negative Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases

ClinicalTrials.gov processed this record on November 25, 2014