Biomarker Study of Pts With Metastatic ccRCC Undergoing Sequential Therapy With 1st Line Sunitinib and 2nd Line Axitinib

Phase 2

• Conditions: Clear Cell Renal Cell Carcinoma
• Interventions: Drug: Sunitinib

• Registration Number: NCT03592199
• Lead Sponsor: Instituto do Cancer do Estado de São Paulo

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.

Study Timeline

• Study Start: 2017-12-11
• Study First Submitted: 2017-12-27
• Study First Submitted QC: 2018-07-17
• Study First Posted: 2018-07-19
• Status Verified: 2019-09
• Last Update Submitted: 2019-09-02
• Last Update Posted: 2019-09-04
• Primary Completion: 2019-12-11
• Study Completion: 2022-12-11

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 7

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:

  1. Are asymptomatic
  2. No evidence of active CNS metastases for ≥3 months prior to enrolment
  3. Have no requirement for steroids or anticonvulsants

• Clinically significant gastrointestinal abnormalities including, but not limited to:

  1. Malabsorption syndrome
  2. Major resection of the stomach or small bowel that could affect the absorption of study drug
  3. Active peptic ulcer disease
  4. Inflammatory bowel disease
  5. Ulcerative colitis, or other gastrointestinal conditions with increased risk of perforation
  6. History of abdominal fistula, gastrointestinal perforation, or intraabdominal abscess within 28 days prior to beginning study treatment.

• History of any one or more of the following cardiovascular conditions within the past 12 months:

  1. Cardiac angioplasty or stenting
  2. Myocardial infarction
  3. Unstable angina
  4. Symptomatic peripheral vascular disease
  5. Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA)
  6. History of cerebrovascular accident including transient ischemic attack (TIA).
  7. Poorly controlled hypertension [defined as systolic blood pressure (SBP) of ≥150 millimeters of mercury (mmHg) or diastolic blood pressure (DBP) of ≥ 90 mmHg

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
1st Line Sunitinib and 2nd Line Axitinib	Sunitinib	1st line sunitinib on a 4/2 schedule followed by axitinib 5 mg twice a day on 2nd line therapy

Primary Outcome Measures

Name	Time	Method
1st line Response Rate (RR) with Sunitinib in patients with VEGF pathway mutation	through study completion (up to 2 years)	First Line Response Rate (RR) With Sunitinib (RECIST 1.1) in patients with VEGF pathway mutation

Secondary Outcome Measures

Name	Time	Method
1sr line RR with Sunitinib	through study completion (up to 2 years)	First Line Response Rate (RR) with Sunitinib (RECIST 1.1)
2nd Line RR with Axitinib	through study completion (up to 2 years)	Second Line Response Rate (RR) with Axitinib (RECIST 1.1)
1st line PFS with Sunitinib	through study completion (up to 2 years)	First Line Progression Free Survival (PFS) with Sunitinib
2nd PFS with Axitinib	through study completion (up to 2 years)	Second Line Progression Free Survival (PFS) with Axitinib
Overall Survival (OS)	through study completion (up to 2 years)	Overall Survival
Incidence of Treatment-Emergent Adverse Events	through study completion (up to 2 years)	CTCAE v.4.0

Trial Locations

Locations (1)

Instituto do Cancer do Estado de São Paulo; 🇧🇷 São Paulo, Brazil