Cabozantinib for Adults With Advanced Soft Tissue Sarcoma

Phase 2

Completed

Conditions: Refractory Soft Tissue Sarcomas

Interventions: Drug: Cabozantinib

Registration Number: NCT01755195

Lead Sponsor: National Cancer Institute (NCI)

Brief Summary: Background:

- Cabozantinib is a cancer treatment drug that blocks the growth of new blood vessels in tumors. It can also block a chemical on tumor cells that allows the cells to grow. A similar drug, pazopanib, is used to treat types of cancer known as sarcomas. Researchers want to see if cabozantinib can be an effective treatment for types of soft tissue sarcoma that have not responded to earlier treatments.

Objectives:

- To test the effectiveness of cabozantinib for soft tissue sarcomas that have not responded to standard treatments.

Eligibility:

- Individuals at least 18 years of age who have soft tissue sarcomas that have not responded to standard treatments.

Design:

* Participants will be screened with a physical exam and medical history. Blood samples will be collected. Imaging studies and other tests will be used to study the tumor before the start of treatment.

* Participants will take cabozantinib tablets daily for 28-day cycles of treatment. The tablets should be taken whole on an empty stomach.

* Treatment will be monitored with frequent blood tests and imaging studies.

* Participants will continue to take cabozantinib for as long as the tumor does not become worse and the side effects are not too severe.

Detailed Description: Background:

* Soft tissue sarcomas (STS) are a relatively rare heterogeneous group of tumors that constitute about 1% of adult cancers.

* The mainstay of treatment for advanced disease has been palliative chemotherapy with a median overall survival of approximately 12 months. This has not changed considerably in the past years and there is an unmet need for newer targeted therapies.

* Vascular endothelial growth factor (VEGF) levels are elevated in patients with STS and various sarcoma cell lines express high levels of activated c-Met receptor.

* We hypothesize that dual targeting of the VEGF and mesenchymal-epithelial transition factor (c-MET) pathways with cabozantinib would result in clinical benefit in patients with soft tissue sarcoma.

Objectives:

Primary:

* Assess the response rate (Complete Response (CR)+Partial Response (PR) of cabozantinib in patients with soft tissue sarcomas.

* Assess the 6 month progression free survival (PFS) of cabozantinib in soft tissue sarcomas.

Secondary:

-Determine and compare circulating levels of hepatocyte growth factor (HGF), soluble MET (sMET), VEGF-A, and soluble vascular endothelial growth factor receptor 2 (VEGFR2) (sVEGFR2) prior to and following administration of cabozantinib.

Eligibility:

* Patients must have had disease progression following one line of standard therapy

* Age greater than or equal to 18 years.

* Adequate organ function.

Design:

* All patients will receive cabozantinib at 60 mg by mouth (PO) daily in 4 week cycles.

* Tumor response evaluations by imaging will be done every 2 cycles (less frequently for patients on study more than one year).

* The study will be conducted as a dual-endpoint two-stage Phase II trial to target objective tumor response rate (CR+PR) of 30% against an unacceptably low rate of 10%, and 6-month PFS rate of 65% against an unacceptably low rate of 45% (corresponding to median PFS of 9.6 vs. 5.2 months).

* The trial will accrue up to 55 patients.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 55

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Cabozantinib	Cabozantinib	60 mg tablets orally once a day in a 28-day cycle.

Primary Outcome Measures

Name	Time	Method
Objective Response (Complete Response (CR)+Partial Response (PR) of Cabozantinib in Patients With Soft Tissue Sarcomas	Date treatment consent signed to date off study, approximately 86 months and 3 days.	Objective response was assessed by the Response Evaluation Criteria in Solid Tumors RECIST) v1.1. Complete Response is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Percentage of Participants With 6 Month Progression Free Survival (PFS)	6 months	Progression in participants with soft tissue sarcomas treated with cabozantinib was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Progression is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. The appearance of one or more new lesions is also considered progressions.

Secondary Outcome Measures

Name	Time	Method
Mean Change From Baseline in Levels of Circulating Hepatocyte Growth Factor (HGF)	Baseline to Cycle 1 Day 1 and baseline to Cycle 2 Day 1	Blood samples were collected before treatment on the first day of cycles 1 and 2 to determine circulating levels of HGF. HGF protein content (in picograms; pg) in blood plasma (in milliliters; mL) was measured for each sample with a two-site immunoassay and the difference from before to after treatment for each patient was reported. A change in this biomarker from the baseline value has not been linked to clinical outcomes; that is, it is neither a good or a bad outcome.
Mean Change From Baseline in Levels of Circulating Soluble Mesenchymal Epithelial Transition Factor (sMET)	Baseline to Cycle 1 Day 1 and baseline to Cycle 2 Day 1	Blood samples were collected before treatment on the first day of cycles 1 and 2 to determine circulating levels of soluble MET (sMET). sMET protein content (in nanograms; ng) in blood plasma (in milliliters; mL) was measured for each sample with a two-site immunoassay and the difference from before to after treatment for each patient was reported. A change in this biomarker from the baseline value has not been linked to clinical outcomes; that is, it is neither a good or a bad outcome.
Mean Change From Baseline in Levels of Circulating Vascular Endothelial Growth Factor A (VEGF-A)	Baseline to Cycle 1 Day 1 and baseline to Cycle 2 Day 1	Blood samples were collected before treatment on the first day of cycles 1 and 2 to determine circulating levels of VEGF-A. VEGF-A protein content (in picograms; pg) in blood plasma (in milliliters; mL) was measured for each sample with a two-site immunoassay and the difference from before to after treatment for each patient was reported. A change in this biomarker from the baseline value has not been linked to clinical outcomes; that is, it is neither a good or a bad outcome.
Mean Change From Baseline in Levels of Circulating Soluble Vascular Endothelial Growth Factor Receptor 2 (sVEGFR-2)	Baseline to Cycle 1 Day 1 and baseline to Cycle 2 Day 1	Blood samples were collected before treatment on the first day of cycles 1 and 2 to determine circulating levels of soluble VEGFR2 (sVEGFR-2). sVEGFR-2 protein content (in nanograms; ng) in blood plasma (in milliliters; mL) was measured for each sample with a two-site immunoassay and the difference from before to after treatment for each patient was reported. A change in this biomarker from the baseline value has not been linked to clinical outcomes; that is, it is neither a good or a bad outcome..