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

Biomarker Study of Patients With Metastatic Clear Cell Renal Carcinoma (ccRCC) Undergoing Sequential Therapy With 1st Line Sunitinib and 2nd Line Axitinib

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.

Study Overview

• Status: Unknown
• Conditions: Clear Cell Renal Cell Carcinoma
• Intervention / Treatment: Drug: Sunitinib

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 Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 2

Contacts and Locations

Study Locations

• Brazil
  • São Paulo, Brazil, 01246000
    • Instituto do Cancer do Estado de Sao Paulo

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 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	Drug: Sunitinib; 1st line sunitinib on a 4/2 schedule followed by axitinib 5 mg twice a day on 2nd line therapy; Other Names: Axitinib

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Instituto do Cancer do Estado de São Paulo
• Collaborators: Pfizer

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 11, 2017
• Primary Completion (ANTICIPATED): December 11, 2019
• Study Completion (ANTICIPATED): December 11, 2022

Study Registration Dates

• First Submitted: December 27, 2017
• First Submitted That Met QC Criteria: July 17, 2018
• First Posted (ACTUAL): July 19, 2018

Study Record Updates

• Last Update Posted (ACTUAL): September 4, 2019
• Last Update Submitted That Met QC Criteria: September 2, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: sunitinib; biomarker; axitinib; metastatic; clear cell renal cell carcinoma; next generation sequencing
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Carcinoma, Renal Cell; Carcinoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Protein Kinase Inhibitors; Sunitinib; Axitinib
• Other Study ID Numbers: NP 1096/17

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No