Randomized Phase II Study Comparing Cabozantinib (NSC #761968) With Commercially Supplied Sunitinib in Patients With Previously Untreated Locally Advanced or Metastatic Renal Cell Carcinoma
Overview
- Phase
- Phase 2
- Intervention
- Cabozantinib S-malate
- Conditions
- Clear Cell Renal Cell Carcinoma
- Sponsor
- National Cancer Institute (NCI)
- Enrollment
- 157
- Locations
- 486
- Primary Endpoint
- Progression Free Survival (PFS)
- Status
- Completed
- Last Updated
- 5 years ago
Overview
Brief Summary
This randomized phase II trial studies how well cabozantinib-s-malate works compared to sunitinib malate in treating patients with previously untreated kidney cancer that has spread from where it started to nearby tissue or lymph nodes or to other places in the body. Cabozantinib-s-malate and sunitinib malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether cabozantinib-s-malate is more effective than sunitinib malate in treating patients with kidney cancer.
Detailed Description
PRIMARY OBJECTIVES: I. To determine if patients with renal cancer treated with cabozantinib (cabozantinib-s-malate) will have improved progression-free survival compared to patients treated with sunitinib (sunitinib malate). SECONDARY OBJECTIVES: I. To determine whether the response rate of patients with renal cancer treated with cabozantinib will be higher when compared with patients treated with sunitinib. II. To determine whether patients with renal cancer treated with cabozantinib will have an improved overall survival when compared with patients treated with sunitinib. TERTIARY OBJECTIVES: I. To determine whether renal cancer patients with high MET expression by immunohistochemistry (IHC) have improvement in progression-free survival compared to patients with low MET expression on both arms of this study. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive cabozantinib-s-malate orally (PO) once daily (QD) for 6 weeks. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive sunitinib malate PO QD for 4 weeks. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 6 months for 5 years.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Renal cell carcinoma with some component of clear cell histology; histologic documentation of metastatic disease is not required
- •Locally advanced (defined as disease not amenable to curative surgery or radiation therapy) or metastatic renal cell carcinoma (RCC) (equivalent to stage IV RCC, according to American Joint Committee on Cancer \[AJCC\] staging)
- •Eligible patients must be intermediate/poor risk, per the International Metastatic Renal Cell Carcinoma (mRCC) Database Consortium (Heng) criteria; patients must therefore have as one or more of the following six factors:
- •Time from diagnosis of RCC to systemic treatment \< 1 year
- •Note: systemic treatment refers to the initiation of A031203 protocol treatment
- •Hemoglobin \< the lower limit of normal (LLN)
- •Corrected calcium \> the upper limit of normal (ULN)
- •Karnofsky performance status \< 80%
- •Neutrophil count \> ULN
- •Platelet count \> ULN
Exclusion Criteria
- Not provided
Arms & Interventions
Arm I (cabozantinib-s-malate)
Patients receive cabozantinib-s-malate PO QD for 6 weeks. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.
Intervention: Cabozantinib S-malate
Arm I (cabozantinib-s-malate)
Patients receive cabozantinib-s-malate PO QD for 6 weeks. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.
Intervention: Laboratory Biomarker Analysis
Arm II (sunitinib malate)
Patients receive sunitinib malate PO QD for 4 weeks. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.
Intervention: Laboratory Biomarker Analysis
Arm II (sunitinib malate)
Patients receive sunitinib malate PO QD for 4 weeks. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.
Intervention: Sunitinib Malate
Outcomes
Primary Outcomes
Progression Free Survival (PFS)
Time Frame: Up to 5 years
Progression free survival (PFS) was investigator assessed and is measured from the beginning of treatment until patient progression or death. Progression was determined using RECIST 1.1 criteria, progression is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).The primary analysis will be based on the stratified log-rank statistic to compare the two treatment arms on PFS. The Kaplan-Meier product-limit estimator will be used to estimate PFS distributions.Progression Free Survival was assessed per investigator, as this was the protocol-specified endpoint, and both investigator and independent review analyses of the PFS endpoint have been published
Overall Survival (OS)
Time Frame: Up to 5 years
The primary analysis will be based on the stratified log-rank statistic to compare the two treatment arms on OS. The Kaplan-Meier product-limit estimator will be used to estimate OS distributions.
Secondary Outcomes
- Objective Response Rates(Up to 5 years)