Parallel (Randomized) Phase II Evaluation of ARQ 197 and ARQ 197 in Combination With Erlotinib in Papillary Renal Cell Carcinoma
Overview
- Phase
- Phase 2
- Intervention
- Laboratory Biomarker Analysis
- Conditions
- Recurrent Renal Cell Carcinoma
- Sponsor
- National Cancer Institute (NCI)
- Enrollment
- 55
- Locations
- 214
- Primary Endpoint
- Response Rate (Confirmed Complete Response or Partial Response), Determined According to Response Evaluation Criteria in Solid Tumors
- Status
- Completed
- Last Updated
- 7 years ago
Overview
Brief Summary
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.
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients must have histologically or cytologically confirmed papillary histology renal cell carcinoma which is metastatic, or locally advanced and unresectable; mixed histologies will be allowed provided that they contain \>= 50% of the papillary component
- •Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension; x-rays, scans or physical examinations used for tumor measurement must have been completed within 28 days prior to registration; x-rays, scans or physical examinations for non-measurable disease must have been completed within 42 days prior to registration; all disease must be assessed and documented on the Baseline Tumor Assessment form
- •Patients with metastatic disease who have a resectable primary tumor and are deemed a surgical candidate may have undergone resection; at least 28 days must have elapsed since surgery and patient must have recovered from any adverse effects of surgery
- •Patients with a history of brain metastases who are asymptomatic and have not received steroid therapy in the 14 days prior to registration are eligible; anti-seizure medications are allowed provided they are non-enzyme inducing (e.g. topiramate, levetiracetam, gabapentin)
- •Patients may have received up to one prior systemic therapy for advanced or metastatic renal cell carcinoma; patients must not have received a MET inhibitor or erlotinib as prior therapy; at least 21 days must have elapsed since completion of prior systemic therapy, 42 days for nitrosoureas or mitomycin C; patients must have recovered from all associated toxicities at the time of registration
- •Patients may have received prior radiation therapy, but must have measurable disease outside the radiation port; at least 21 days must have elapsed since completion of prior radiation therapy; patients must have recovered from all associated toxicities at the time of registration
- •Patients must not be receiving or planning to receive any other investigational agents
- •Patients must have a complete physical examination and medical history within 28 days prior to registration
- •Patients must have a Zubrod performance status of 0-2
- •White blood cell (WBC) \>= 2,000/mcL
Exclusion Criteria
- Not provided
Arms & Interventions
Arm I (tivantinib)
Patients receive tivantinib PO BID on days 1-28.
Intervention: Laboratory Biomarker Analysis
Arm I (tivantinib)
Patients receive tivantinib PO BID on days 1-28.
Intervention: Tivantinib
Arm II (tivantinib and erlotinib hydrochloride)
Patients receive tivantinib PO BID and erlotinib hydrochloride PO QD on days 1-28.
Intervention: Erlotinib Hydrochloride
Arm II (tivantinib and erlotinib hydrochloride)
Patients receive tivantinib PO BID and erlotinib hydrochloride PO QD on days 1-28.
Intervention: Laboratory Biomarker Analysis
Arm II (tivantinib and erlotinib hydrochloride)
Patients receive tivantinib PO BID and erlotinib hydrochloride PO QD on days 1-28.
Intervention: Tivantinib
Outcomes
Primary Outcomes
Response Rate (Confirmed Complete Response or Partial Response), Determined According to Response Evaluation Criteria in Solid Tumors
Time Frame: Up to 3 years
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.
Secondary Outcomes
- Progression-free Survival (PFS)(30 months)
- Frequency and Severity of Toxicities, Graded by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0(Up to 3 years)