CompletedNCT01738438Updated Dec 6, 2016Results posted

Cabozantinib for Metastatic Triple Negative BrCa

A Phase 2 interventional study of Cabozantinib in Breast Cancer, sponsored by Dana-Farber Cancer Institute. Completed at 3 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2016-12-06.

Sponsored by Dana-Farber Cancer Institute · Phase 2, Interventional, and Treatment

Phase: Phase 2
Study type: Interventional
Enrollment: 35
Allocation: Not applicable
Ages: 18 Years and older
Sex: All

Study summary

In this research study, we are looking at the anti-tumor effects of Cabozantinib (XL184) in metastatic breast cancer. Data suggest that MET expression and activation are important for initiation and progression of triple-negative breast cancer (TNBC). We evaluated the efficacy of cabozantinib (XL184), a novel inhibitor of multiple receptor tyrosine kinases, including MET and VEGFR2, in patients with metastatic TNBC.

Read the detailed description

OBJECTIVES:

Primary

* To evaluate the activity of cabozantinib, as defined by objective response rate in patients with triple-negative metastatic breast cancer

Secondary

To evaluate progression free survival
To evaluate c-Met and phospho c-Met expression in archival tumor tissue
To evaluate the incidence of c-Met amplified circulating tumor cells at baseline
To evaluate potential plasma biomarkers of cabozantinib

DESIGN:

This study uses a two-stage design enrolling 35 patients to evaluate efficacy of cabozantinib based on overall response defined as complete or partial response per RECIST1.1 criteria. The null and alternative overall response rates were 5% and 20%. If one or more patients enrolled in the stage one cohort (n=13 patients) achieve PR or better then accrual proceeds to stage two (n=22 patients).

Conditions studied

Breast Cancer

Browse trials for

Breast Neoplasms 12,544

Keywords

Metastatic
Triple Negative
Stage IV

In context

Breast Neoplasms

12,544 studies on the registry are indexed under Breast Neoplasms; 2,892 are open to participants now.

This study's enrollment of 35 is below the median of 72 across 9,303 interventional studies indexed under Breast Neoplasms.

Browse Breast Neoplasms studies →

Lead sponsor

Dana-Farber Cancer Institute is the lead sponsor of 813 studies on the registry; 124 are open to participants now.

Of its 113 completed or terminated interventional studies of FDA-regulated products, 77 (68%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

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

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

Phase: Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrollment: 35 participants (actual)

Study arms

Experimental
Cabozantinib
Cabozantinib was given at a dose of 60 mg orally once per day for 21 day cycles. Treatment continued in the absence of disease progression or unacceptable toxicity.
Drug: Cabozantinib

Interventions

DrugCabozantinib
Also known as: XL184

What researchers measure

Primary outcomes

Objective Response Rate
The objective response rate (ORR) was defined as achieving complete response (CR) or partial response (PR) on treatment based on RECIST1.1 criteria. 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. 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. Confirmatory scans were required 3 weeks following initial documentation.
Time frame: Disease was evaluated radiologically at baseline, week 6 and every 9 weeks on treatment; Treatment continued until disease progression or unacceptable toxicity. Treatment duration was a median of 3 cycles range (1-17).

Secondary outcomes

Progression Free Survival
Progression-free survival (PFS) estimated using Kaplan-Meier methods was defined as the time from registration to documented disease progression (PD) or death. Based on RECIST1.1, radiographic PD is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum since beginning therapy, the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Patients who were event-free were censored at the date of their last disease evaluation.
Time frame: Disease was evaluated radiologically at baseline, week 6 and every 9 weeks on treatment; Treatment continued until disease progression or unacceptable toxicity. Treatment duration was a median of 3 cycles range (1-17).

Results

Posted Jul 7, 2016

Participant flow

Patients enrolled from January 2013 through June 2014.

Participant flow — Overall Study
Milestone	Cabozantinib
Started	35
Completed	0
Not completed	35
Withdrew: Disease progression	32
Withdrew: Adverse event	3

Outcome measures

PrimaryObjective Response Rate

The objective response rate (ORR) was defined as achieving complete response (CR) or partial response (PR) on treatment based on RECIST1.1 criteria. 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. 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. Confirmatory scans were required 3 weeks following initial documentation.

Time frame:: Disease was evaluated radiologically at baseline, week 6 and every 9 weeks on treatment; Treatment continued until disease progression or unacceptable toxicity. Treatment duration was a median of 3 cycles range (1-17).
Reported as:: Number · proportion of participants

Objective Response Rate
proportion of participants	Cabozantinib
Objective Response Rate	0.09 (0.02 to 0.26)

SecondaryProgression Free Survival

Progression-free survival (PFS) estimated using Kaplan-Meier methods was defined as the time from registration to documented disease progression (PD) or death. Based on RECIST1.1, radiographic PD is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum since beginning therapy, the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Patients who were event-free were censored at the date of their last disease evaluation.

Time frame:: Disease was evaluated radiologically at baseline, week 6 and every 9 weeks on treatment; Treatment continued until disease progression or unacceptable toxicity. Treatment duration was a median of 3 cycles range (1-17).
Reported as:: Median · months

Progression Free Survival
months	Cabozantinib
Progression Free Survival	2 (1.3 to 3.3)

Post-hoc15-Week Clinical Benefit Rate

The 15-week clinical benefit rate (CBR) was defined as absence of disease progression (PD) per RECIST1.1 criteria at the second disease assessment (week 15). Radiographic PD is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum since beginning therapy, the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Confirmatory scans for response were required 3 weeks following initial documentation.

Time frame:: Disease was evaluated radiologically at baseline, week 6 and week 15 on treatment.
Reported as:: Number · proportion of participants

15-Week Clinical Benefit Rate
proportion of participants	Cabozantinib
15-Week Clinical Benefit Rate	.34 (.19 to 0.52)

Adverse events

Collected over Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in cycles was a median (range) of 3 (1-17).. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Cabozantinib	—	14/35 (40%)	34/35 (97.1%)

Most frequent serious events

Showing 10 of 11

Most frequent serious events
Event	Cabozantinib
Lipase increasedInvestigations	3/35
Aspartate aminotransferase increasedInvestigations	2/35
Bone painMusculoskeletal and connective tissue disorders	2/35
HypertensionVascular disorders	2/35
Infections and infestations - OtherInfections and infestations	1/35
Wound dehiscenceInjury, poisoning and procedural complications	1/35
Activated partial thromboplastin time prolongedInvestigations	1/35
Alanine aminotransferase increasedInvestigations	1/35
HypophosphatemiaMetabolism and nutrition disorders	1/35
Palmar-plantar erythrodysesthesia syndromeSkin and subcutaneous tissue disorders	1/35

Most frequent other events

Showing 10 of 57

Most frequent other events
Event	Cabozantinib
FatigueGeneral disorders	26/35
Gastrointestinal disorders - OtherGastrointestinal disorders	19/35
DiarrheaGastrointestinal disorders	14/35
Mucositis oralGastrointestinal disorders	13/35
AnorexiaMetabolism and nutrition disorders	12/35
Palmar-plantar erythrodysesthesia syndromeSkin and subcutaneous tissue disorders	12/35
NauseaGastrointestinal disorders	10/35
Aspartate aminotransferase increasedInvestigations	9/35
DysgeusiaNervous system disorders	7/35
HypertensionVascular disorders	7/35

Baseline characteristics

The analysis dataset is comprised of all treated patients.

Age, Continuous
Age, Continuous(years)	Cabozantinib
Median	50 (31 to 78)

Gender
Gender(Participants)	Cabozantinib
Female	35
Male	0

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	Cabozantinib
American Indian or Alaska Native	0
Asian	0
Native Hawaiian or Other Pacific Islander	0
Black or African American	3
White	32
More than one race	0
Unknown or Not Reported	0

Region of Enrollment
Region of Enrollment(participants)	Cabozantinib
United States	35

Study locations

3 sites

Dana-Farber Cancer Institute at Faulkner Hospital
Boston, Massachusetts 02130, United States
Massachusetts General Hospital
Boston, Massachusetts 02214, United States
Dana-Farber Cancer Institute
Boston, Massachusetts 02215, United States

References and documents

Publications

Weber ZT, Collier KA, Tallman D, Forman J, Shukla S, Asad S, Rhoades J, Freeman S, Parsons HA, Williams NO, Barroso-Sousa R, Stover EH, Mahdi H, Cibulskis C, Lennon NJ, Ha G, Adalsteinsson VA, Tolaney SM, Stover DG. Modeling clonal structure over narrow time frames via circulating tumor DNA in metastatic breast cancer. Genome Med. 2021 May 20;13(1):89. doi: 10.1186/s13073-021-00895-x. PubMed 34016182 ↗

Individual participant data

Plan to share: No

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Dec 6, 2016, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT01738438
Lead sponsor: Dana-Farber Cancer Institute
Responsible party: Sara Tolaney (Prinicipal Investigator, Dana-Farber Cancer Institute) — Principal investigator
First posted: Nov 30, 2012
Start date: Feb 2013
Primary completion: May 2015
Completion: May 2015
Results posted: Jul 7, 2016
Last update: Dec 6, 2016

Study contacts

Sara Tolaney, MD, MPH

principal investigator · Dana-Farber Cancer Institute

Oversight

Data monitoring committee: Yes

View the source record on ClinicalTrials.gov ↗

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