Cabozantinib for Metastatic Triple Negative BrCa

Breast Cancer Clinical Trial

Official title:

A Phase II Study of XL184 (Cabozantinib) for Metastatic Triple-Negative Breast Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01738438
• Other study ID #: 12-431
• Status: Completed
• Phase: Phase 2
• First received: November 28, 2012
• Last updated: November 17, 2015
• Start date: February 2013
• Est. completion date: October 2014

Study information

• Verified date: November 2015
• Source: Dana-Farber Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 35
• Est. completion date: October 2014
• Est. primary completion date: October 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer

Intervention

Drug:
• XL184

Locations

Country	Name	City	State
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Dana-Farber Cancer Institute at Faulkner Hospital	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Dana-Farber Cancer Institute

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evaluation of XL184 based on objective response rate	To evaluate the activity of XL184, as defined by objective response rate (ORR) in patients with triple-negative metastatic breast cancer	2 years	No
Secondary	Progression Free Survival	Evaluation of Progression Free Survival	2 years	No
Secondary	c-Met and phospho c-Met expression	To evaluate c-Met and phospho c-Met expression in archival tumor tissue	2 years	No
Secondary	Incidence of c-Met amplified circulating tumor cells	To evaluate the incidence of c-Met amplified circulating tumor cells at baseline	2 years	No
Secondary	Evaluation of potential serum biomarkers	Evaluate potential serum biomarkers of XL184	2 years	No
Secondary	Evaluate PTEN loss and PI3K mutations	To evaluate PTEN loss and PI3K mutations in archival tumor tissue	2 years	No
Secondary	Evaluate change in radiotracer uptake within tumor site	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	2 years	No