This randomized phase II trial studies how well tivantinib with or without erlotinib hydrochloride works in treating patients with metastatic or locally advanced kidney cancer that cannot be removed by surgery. Tivantinib and erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
PRIMARY OBJECTIVES: I. To assess the response rate (confirmed complete and partial response) of patients with locally advanced or metastatic papillary renal cell carcinoma treated with either ARQ 197 (tivantinib) or ARQ 197 combined with erlotinib (erlotinib hydrochloride). SECONDARY OBJECTIVES: I. To assess the progression free survival (PFS) of patients with locally advanced or metastatic papillary renal cell carcinoma treated with either ARQ 197 or ARQ 197 combined with erlotinib. II. To assess the safety and tolerability of ARQ 197 therapy and ARQ 197 combined with erlotinib. III. To descriptively assess the role of prior treatment on outcome. TERTIARY OBJECTIVES: I. To bank tissue specimens for future use and once funding is obtained to evaluate the expression of tissue correlative biomarkers such as hepatocyte growth factor receptor (c-MET) and epidermal growth factor receptor (EGFR), and to perform exploratory correlation with clinical outcomes. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive tivantinib orally (PO) twice daily (BID) on days 1-28. ARM II: Patients receive tivantinib PO BID and erlotinib hydrochloride PO once daily (QD) on days 1-28. In both arms, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 1 year and then every 6 months for up to 2 years.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
55
150 mg (1 tablet) by mouth on days 1-28, once daily, until disease progression
Correlative studies
360 mg (3 tablets) by mouth, Twice daily (720 mg total daily dose) on days 1-28, until disease progression
University of Arizona Cancer Center-Orange Grove Campus
Tucson, Arizona, United States
University of Arizona Cancer Center-North Campus
Tucson, Arizona, United States
The University of Arizona Medical Center-University Campus
Tucson, Arizona, United States
Kaiser Permanente-Anaheim
Anaheim, California, United States
Kaiser Permanente-Baldwin Park
Baldwin Park, California, United States
Response Rate (Confirmed Complete Response or Partial Response), Determined According to Response Evaluation Criteria in Solid Tumors
Best Response is calculated from the sequence of objective statuses. CR: Two or more objective statuses of CR a minimum of four weeks apart documented before progression or symptomatic deterioration. PR: Two or more objective statuses of PR or better a minimum of four weeks apart documented before progression or symptomatic deterioration, but not qualifying as CR. Stable/no response: At least one objective status of stable/no response documented at least 6 weeks after registration and before progression or symptomatic deterioration, but not qualifying as anything else above. Increasing disease: Objective status of progression within 12 weeks of registration, not qualifying as anything else above. Symptomatic deterioration: Objective status of symptomatic deterioration within 12 weeks of registration, not qualifying as anything else above.
Time frame: Up to 3 years
Frequency and Severity of Toxicities, Graded by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
This study utilized the CTCAE (NCI Common Terminology Criteria for Adverse Events) Version 4.0 for toxicity and Serious Adverse Event reporting. Patients were evaluated every two weeks for the first eight weeks and then once every four weeks. If all protocol treatment is delayed more than three weeks, patients were removed from protocol treatment
Time frame: Up to 3 years
Progression-free Survival (PFS)
From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause. Patients last known to be alive without report of progression are censored at date of last contact.
Time frame: 30 months
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Kaiser Permanente-Bellflower
Bellflower, California, United States
Alta Bates Summit Medical Center-Herrick Campus
Berkeley, California, United States
Mills-Peninsula Medical Center
Burlingame, California, United States
City of Hope Comprehensive Cancer Center
Duarte, California, United States
Kaiser Permanente Hospital
Fontana, California, United States
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