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

• ClinicalTrials.gov Identifier: NCT03592199
• Recruitment Status: Unknown
• First Posted: July 19, 2018
• Last Update Posted: September 4, 2019
• Sponsor: Instituto do Cancer do Estado de São Paulo
• Collaborator: Pfizer
• Information provided by (Responsible Party): Instituto do Cancer do Estado de São Paulo

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Clear Cell Renal Cell Carcinoma	Drug: Sunitinib	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 7 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Biomarker Study of Patients With Metastatic Clear Cell Renal Carcinoma (ccRCC) Undergoing Sequential Therapy With 1st Line Sunitinib and 2nd Line Axitinib
• Actual Study Start Date: December 11, 2017
• Estimated Primary Completion Date: December 11, 2019
• Estimated Study Completion Date: December 11, 2022

Arms and Interventions

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 Name: Axitinib

Outcome Measures

Primary Outcome Measures :

1. 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 Outcome Measures :

1. 1sr line RR with Sunitinib [ Time Frame: through study completion (up to 2 years) ]
   First Line Response Rate (RR) with Sunitinib (RECIST 1.1)
2. 2nd Line RR with Axitinib [ Time Frame: through study completion (up to 2 years) ]
   Second Line Response Rate (RR) with Axitinib (RECIST 1.1)
3. 1st line PFS with Sunitinib [ Time Frame: through study completion (up to 2 years) ]
   First Line Progression Free Survival (PFS) with Sunitinib
4. 2nd PFS with Axitinib [ Time Frame: through study completion (up to 2 years) ]
   Second Line Progression Free Survival (PFS) with Axitinib
5. Overall Survival (OS) [ Time Frame: through study completion (up to 2 years) ]
   Overall Survival
6. Incidence of Treatment-Emergent Adverse Events [ Time Frame: through study completion (up to 2 years) ]
   CTCAE v.4.0

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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:

  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

Contacts and Locations

Locations

Brazil

Instituto do Cancer do Estado de São Paulo

São Paulo, Brazil, 01246000

Sponsors and Collaborators

Instituto do Cancer do Estado de São Paulo

Pfizer

More Information

• Responsible Party: Instituto do Cancer do Estado de São Paulo
• ClinicalTrials.gov Identifier: NCT03592199
• Other Study ID Numbers: NP 1096/17
• First Posted: July 19, 2018
• Last Update Posted: September 4, 2019
• Last Verified: September 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• 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

Keywords provided by Instituto do Cancer do Estado de São Paulo:

biomarker; metastatic; sunitinib; axitinib; next generation sequencing; clear cell renal cell carcinoma

Additional relevant MeSH terms:

Carcinoma; Carcinoma, Renal Cell; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Sunitinib; Axitinib; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Physiological Effects of Drugs; Growth Inhibitors; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action