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.
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)
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
36
Massachusetts General Hospital
Boston, Massachusetts, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, United States
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.
Time frame: 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.
CNS Volumetric Objective Response Rate (ORR)
CNS volumetric ORR was defined as the percentage of participants achieving complete response (CR) or partial response (PR) defined as: CR * Complete resolution of all measurable (≥ 1 cm diameter) and non-measurable brain metastases * No new CNS lesions (new lesion defined as ≥ 6 mm diameter) PR * ≥ 50% reduction in the volumetric sum of all measurable (≥ 1 cm diameter) brain metastases compared to baseline * No progression of non-measurable lesions * No new lesions (new lesion defined as ≥ 6 mm) ORR also requires: * Stable or decreasing steroid dose * No new/progressive tumor-related neurologic signs or symptoms
Time frame: 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)
The non-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 non-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.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Time frame: 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)
Progression-free survival based on the Kaplan-Meier method is defined as the duration of time from study entry to documented disease progression (PD) or death. Per RECIST 1.1 criteria: progressive disease (PD) is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions.
Time frame: 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
Clinical benefit rate (CBR) was defined as the percentage of patients achieving complete response (CR), partial response (PR), or stable disease (SD) based on RECIST 1.1 criteria by 12 weeks. Per RECIST 1.1 for target lesions: 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. PD is at least a 20% increase in sum LD of target lesions (smallest sum LD reference), new lesions, and/or unequivocal progression of existing non-target lesions. Stable disease (SD) is defined as any condition not meeting the above criteria.
Time frame: Evaluate at 12 weeks.
First Progression Site
Site that a patient has his/her first tumor progression (CNS vs Non-CNS)
Time frame: 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.
Overall Survival (OS)
OS based on the Kaplan-Meier method is defined as the time from study entry to death or censored at date last known alive.
Time frame: Off-treatment patients followed every 6 months until death. Follow-up time is up to 25 months.
Incidence of Grade 4 Treatment-Related Toxicity
All grade 4 adverse events (AE) with treatment attribution of possibly, probably or definite based on CTCAEv4 as reported on case report forms were counted. Incidence is the number of patients experiencing at least one treatment-related grade 4 AE of any type during the time of observation.
Time frame: Participants should be re-evaluated for response every 6 weeks. Patients with stable or responsive disease after completion of 6 cycles may have the frequency of scans reduced to once every 3 cycles, and in long-term follow-up every 6 months until death.