Cabozantinib for Adults With Advanced Soft Tissue Sarcoma

NCT01755195 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 13004413-C-0044
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 1

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.

Conditions

Refractory Soft Tissue Sarcomas

Keywords

Dual Inhibitor of MET and VEGFR; XL184; Metastatic Refractory; Soft Tissue Sarcoma; Rare Heterogeneous Tumor

Outcome Measures

Primary Outcomes (2)

• Objective Response (Complete Response (CR)+Partial Response (PR) of Cabozantinib in Patients With Soft Tissue Sarcomas

  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.

  Date treatment consent signed to date off study, approximately 86 months and 3 days.

• Percentage of Participants With 6 Month Progression Free Survival (PFS)

  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.

  6 months

Secondary Outcomes (4)

• 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

• 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

• 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

• 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

Other Outcomes (1)

• Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0)

  Date treatment consent signed to date off study, approximately 86 months and 3 days.

Study Arms (1)

Cabozantinib

EXPERIMENTAL

60 mg tablets orally once a day in a 28-day cycle.

Drug: Cabozantinib

Interventions

Cabozantinib DRUG

Cabozantinib inhibits multiple receptor tyrosine kinases (RTKs) implicated in tumor growth, metastasis, and angiogenesis, and targets primarily mesenchymal-epithelial transition factor (MET) and vascular endothelial growth factor receptor 2 (VEGFR2).

Also known as: Cometriq

Cabozantinib

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically or cytologically confirmed soft tissue sarcoma that is metastatic or unresectable and for which standard treatment that prolongs survival does not exist or is no longer effective.
• Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as \>20 mm with conventional techniques or as \>10 mm with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam.
• Patients are allowed prior vascular endothelial growth factor receptor (VEGFR)-tyrosine kinase inhibitors (TKI) therapy.
• Age greater than or equal to 18 years. Because no dosing or adverse event data are currently available on the use of cabozantinib in patients \<18 years of age, children are excluded from this study.
• Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 1 (Karnofsky \>70%).
• Life expectancy \> 3 months.
• Patients must have normal organ and marrow function as defined below:
• leukocytes greater than or equal to 3,000/mcL
• absolute neutrophil count greater than or equal to 1,500/mcL
• platelets greater than or equal to 100,000/mcL
• total bilirubin less than or equal to 1.5 times ULN
• Aspartate aminotransferase (AST) serum glutamic oxaloacetic transaminase(SGOT)/alanine aminotransferase (ALT) serum glutamic pyruvic transaminase(SGPT) less than or equal to 2.5 times institutional upper limit of normal creatinine within normal institutional limits
• creatinine within normal institutional limits OR clearance greater than or equal to 60 mL/min/1.73 m(2) for patients with creatinine levels above institutional normal.
• hemoglobin greater than or equal to 9 g/dL
• serum albumin greater than or equal to 2.8g/dL

You may not qualify if:

• Patients who have had anticancer therapy, including kinase inhibitors or any investigational agent within 4 weeks or 5 half-lives (whichever is shorter) (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered to baseline from adverse events (except alopecia and other non-clinically significant adverse events (AEs). Patients who have received prior cabozantinib or inhibitors of tyrosine-protein kinase mesenchymal epithelial transition factor (c-MET) or hepatocyte growth factor (HGF) are ineligible.
• The subject has received radionuclide treatment within 6 weeks of the first dose of study treatment
• The subject has received radiation therapy within 4 weeks (greater than or equal to 2 weeks for palliative radiation therapy)
• Patients with active brain metastases or carcinomatous meningitis or epidural disease are excluded from this clinical trial. Subjects with brain metastases previously treated with whole brain radiation or radiosurgery or subjects with epidural disease previously treated with radiation who are asymptomatic and have remained stable for 4 weeks and do not require steroid treatment for at least 2 weeks before starting study treatment are eligible. Neurosurgical resection of brain metastases or brain biopsy is permitted if completed at least 3 months before starting study treatment. Baseline brain imaging with contrast-enhanced CT or MRI scans for subjects with known brain metastases is required to confirm eligibility.
• Eligibility of subjects receiving any medications or substances known to affect or with the potential to affect the activity of cabozantinib will be determined following review of their cases by the Principal Investigator. Patients who are taking enzyme-inducing anticonvulsant agents are not eligible.
• Patients with refractory nausea and vomiting, chronic gastrointestinal diseases (e.g., inflammatory bowel disease), or significant bowel resection that could interfere with absorption.
• Uncontrolled intercurrent illness including, but not limited to symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant women are excluded from this study because cabozantinib has the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with cabozantinib, breastfeeding should be discontinued if the mother is treated with cabozantinib.
• Strong inhibitors and inducers of cytochrome P450 3A4 (CYP3A4) can affect levels of cabozantinib and should be avoided whenever possible or switched to alternatives. Subjects requiring chronic concomitant treatment of strong CYP3A4 inducers (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital, and St. John's Wort) are not eligible for this study. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated list such as http://medicine.iupui.edu/clinpharm/ddis/; medical reference texts such as the Physicians Desk Reference may also provide this information. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over the-counter medicine or herbal product.
• Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with cabozantinib. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.
• The subject requires concomitant treatment, in therapeutic doses, with anticoagulants such as warfarin or warfarin-related agents, heparin, thrombin or Factor Xa inhibitors, or antiplatelet agents (e.g., clopidogrel). Low dose aspirin (less than or equal to 81 mg/day), low-dose warfarin (less than or equal to 1 mg/day), and prophylactic low molecular weight heparin (LMWH) are permitted. (Please note that there may be cases in which patients on study require anticoagulation for deep vein thrombosis (DVT)/pulmonary embolism (PE) management; this does not necessitate taking
• the patient off study.)
• The subject has experienced any of the following
• clinically-significant gastrointestinal bleeding within 6 months before the first dose of study treatment
• hemoptysis of greater than or equal to 0.5 teaspoon (2.5 mL) of red blood within 3 months before the first dose of study treatment

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Coindre JM, Terrier P, Guillou L, Le Doussal V, Collin F, Ranchere D, Sastre X, Vilain MO, Bonichon F, N'Guyen Bui B. Predictive value of grade for metastasis development in the main histologic types of adult soft tissue sarcomas: a study of 1240 patients from the French Federation of Cancer Centers Sarcoma Group. Cancer. 2001 May 15;91(10):1914-26. doi: 10.1002/1097-0142(20010515)91:103.0.co;2-3.

  PMID: 11346874 BACKGROUND

• Edmonson JH, Ryan LM, Blum RH, Brooks JS, Shiraki M, Frytak S, Parkinson DR. Randomized comparison of doxorubicin alone versus ifosfamide plus doxorubicin or mitomycin, doxorubicin, and cisplatin against advanced soft tissue sarcomas. J Clin Oncol. 1993 Jul;11(7):1269-75. doi: 10.1200/JCO.1993.11.7.1269.

  PMID: 8315424 BACKGROUND

• Elias A, Ryan L, Sulkes A, Collins J, Aisner J, Antman KH. Response to mesna, doxorubicin, ifosfamide, and dacarbazine in 108 patients with metastatic or unresectable sarcoma and no prior chemotherapy. J Clin Oncol. 1989 Sep;7(9):1208-16. doi: 10.1200/JCO.1989.7.9.1208.

  PMID: 2504890 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Sarcoma

Interventions

cabozantinib

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Results Point of Contact

• Title: Dr. Alice Chen
• Organization: National Cancer Institute

chenali@mail.nih.gov

240-781-3274

Study Officials

• Alice P Chen, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 18, 2012
• First Posted: December 24, 2012
• Study Start: January 15, 2013
• Primary Completion: September 30, 2020
• Study Completion: September 11, 2023
• Last Updated: January 3, 2024
• Results First Posted: September 16, 2021

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)