Biomarker Study of Patients With Metastatic Clear Cell Renal Carcinoma (ccRCC) Undergoing Sequential Therapy With 1st Line Sunitinib and 2nd Line Axitinib
Overview
- Phase
- Phase 2
- Intervention
- Sunitinib
- Conditions
- Clear Cell Renal Cell Carcinoma
- Sponsor
- Instituto do Cancer do Estado de São Paulo
- Enrollment
- 7
- Locations
- 1
- Primary Endpoint
- 1st line Response Rate (RR) with Sunitinib in patients with VEGF pathway mutation
- Last Updated
- 6 years ago
Overview
Brief Summary
This is a prospective single arm phase II study to evaluate potential prognostic and/or predictive biomarkers in patients with metastatic ccRCC undergoing treatment with 1st line sunitinib on a 4/2 schedule followed by axitinib on 2nd line therapy.
Detailed Description
In this study, all included patients will receive sunitinib until disease progression and/or limiting toxicity. If patients develop toxicities ≥ Grade 2 on 50 mg per day 4 weeks-on / 2 weeks-off schedule, a modified schedule of 50 mg/day 2 weeks-on / 1 week-off will be offered. After disease progression on sunitinib, all eligible patients will receive axitinib 5 mg twice a day. The investigators plan to assess, by next generation sequencing, the prevalence of mutations in several cancer related genes in baseline archived tissue from the patients included in the study, and the potential correlations between these somatic mutations and anti-VEGF (Vascular Endothelial Growth Factor) therapy efficacy.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Diagnosis of Locally advanced (defined as disease not amenable to curative surgery or radiation therapy) or metastatic RCC (equivalent to Stage IV RCC according to American Joint Committee on Cancer staging) renal cell carcinoma;
- •Histologic confirmed clear cell renal cell carcinoma;
- •No prior systemic therapy (interleukin-2, interferon-α, chemotherapy, bevacizumab, sunitinib, sorafenib, pazopanib, axitinib, everolimus or temsirolimus) for advanced or metastatic RCC;
- •Measurable disease by RECIST;
- •Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 2;
- •Adequate organ system functions;
- •Patients must understand and be willing to sign the written informed consent form of this study.
Exclusion Criteria
- •Non-clear cell renal cell carcinoma
- •Pregnant or lactating female.
- •History of another malignancy. Note: Subjects who have had another malignancy and have been disease-free for 3 years, or subjects with a history of completely resected non-melanoma skin carcinoma or successfully treated in situ carcinoma are eligible.
- •History or clinical evidence of central nervous system (CNS) metastases. Note: Subjects who have previously-treated CNS metastases (surgery ± radiotherapy, radiosurgery) and meet all 3 of the following criteria are eligible:
- •Are asymptomatic
- •No evidence of active CNS metastases for ≥3 months prior to enrolment
- •Have no requirement for steroids or anticonvulsants
- •Clinically significant gastrointestinal abnormalities including, but not limited to:
- •Malabsorption syndrome
- •Major resection of the stomach or small bowel that could affect the absorption of study drug
Arms & Interventions
1st Line Sunitinib and 2nd Line Axitinib
1st line sunitinib on a 4/2 schedule followed by axitinib 5 mg twice a day on 2nd line therapy
Intervention: Sunitinib
Outcomes
Primary Outcomes
1st line Response Rate (RR) with Sunitinib in patients with VEGF pathway mutation
Time Frame: through study completion (up to 2 years)
First Line Response Rate (RR) With Sunitinib (RECIST 1.1) in patients with VEGF pathway mutation
Secondary Outcomes
- 1sr line RR with Sunitinib(through study completion (up to 2 years))
- 2nd Line RR with Axitinib(through study completion (up to 2 years))
- 1st line PFS with Sunitinib(through study completion (up to 2 years))
- 2nd PFS with Axitinib(through study completion (up to 2 years))
- Overall Survival (OS)(through study completion (up to 2 years))
- Incidence of Treatment-Emergent Adverse Events(through study completion (up to 2 years))