Testing Cabozantinib, Crizotinib, Savolitinib and Sunitinib in Kidney Cancer Which Has Progressed
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|ClinicalTrials.gov Identifier: NCT02761057|
Recruitment Status : Active, not recruiting
First Posted : May 4, 2016
Last Update Posted : October 29, 2020
|Condition or disease||Intervention/treatment||Phase|
|Locally Advanced Papillary Renal Cell Carcinoma Metastatic Papillary Renal Cell Carcinoma Stage III Renal Cell Cancer AJCC v7 Stage IV Renal Cell Cancer AJCC v7 Type 1 Papillary Renal Cell Carcinoma Type 2 Papillary Renal Cell Carcinoma Unresectable Renal Cell Carcinoma||Drug: Cabozantinib S-malate Drug: Crizotinib Drug: Savolitinib Drug: Sunitinib Malate||Phase 2|
I. To compare progression-free survival (PFS) in patients with metastatic papillary renal cell carcinoma (mPRCC) treated with sunitinib malate (sunitinib) to PFS in patients with mPRCC treated with MET kinase inhibitors.
I. To compare Response Evaluation Criteria in Solid Tumors (RECIST) response rate (RR; defined as the combined rate of confirmed and unconfirmed partial response [PR] and complete response [CR]) in patients with mPRCC treated with sunitinib to RR in patients treated with putative MET inhibitors.
II. To compare overall survival (OS) in patients with mPRCC treated with sunitinib to OS in patients with mPRCC treated with putative MET inhibitors.
III. To compare the safety profile of sunitinib and putative MET inhibitors in patients with mPRCC.
I. To evaluate the prognostic and predictive value of MET mutations, MET copy number or other markers of MET signaling in patients with mPRCC treated with putative MET inhibitors.
II. To estimate the frequency of high oncometabolite levels in formalin-fixed, paraffin-embedded (FFPE) tissues of patients with advanced papillary renal cell carcinoma by liquid chromatography-mass spectrometry (LC-MS/MS) and estimate progression free survival for those with and without high oncometabolite levels being treated.
III. To correlate the mutational signature suggestive of a homologous recombination defect with high oncometabolite levels in patients with papillary renal cell carcinoma pRCC.
OUTLINE: Patients are randomized to 1 of 4 treatment arms. As of 12/5/18, patients will only be randomized to Arm I or Arm II.
ARM I: Patients receive sunitinib malate orally (PO) once daily (QD) on days 1-28.
ARM II: Patients receive cabozantinib s-malate PO QD on days 1-42.
ARM III (CLOSED TO ACCRUAL 12/5/18): Patients receive crizotinib PO twice daily (BID) on days 1-42.
ARM IV (CLOSED TO ACCRUAL 12/5/18): Patients receive savolitinib PO QD on days 1-42.
In all arms, cycles repeat every 42 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 3 years.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||180 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Randomized, Phase II Efficacy Assessment of Multiple MET Kinase Inhibitors (Cabozantinib [NSC #761968], Crizotinib [NSC #749005], Savolitinib [NSC #785348], and Sunitinib [NSC #736511]) in Metastatic Papillary Renal Carcinoma (PAPMET)|
|Actual Study Start Date :||April 5, 2016|
|Estimated Primary Completion Date :||January 1, 2021|
Experimental: Arm I (sunitinib malate)
Patients receive sunitinib malate PO on days 1-28. Cycles repeat every 42 days in the absence of disease progression or unacceptable toxicity.
Drug: Sunitinib Malate
Experimental: Arm II (cabozantinib s-malate)
Patients receive cabozantinib s-malate PO on days 1-42. Cycles repeat every 42 days in the absence of disease progression or unacceptable toxicity.
Drug: Cabozantinib S-malate
Experimental: Arm III (crizotinib closed to accrual 12/5/18)
Patients receive crizotinib PO BID on days 1-42. Cycles repeat every 42 days in the absence of disease progression or unacceptable toxicity.
Experimental: Arm IV (savolitinib closed to accrual 12/5/18)
Patients receive savolitinib PO on days 1-42. Cycles repeat every 42 days in the absence of disease progression or unacceptable toxicity.
- Progression free survival (PFS) [ Time Frame: From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause; assessed up to 3 years ]A proportional hazards model will be used to evaluate each pair wise treatment comparison of PFS, adjusting for the two stratification factors as covariates in the model.
- Response rate (RR) [ Time Frame: Up to 3 years ]The Chi-Square test will be used to compare RR between the control arm of sunitinib malate and the MET inhibitor treatment arms.
- Overall survival (OS) [ Time Frame: Up to 3 years ]The method of Kaplan and Meier will be used to estimate survival curves. The log-rank test will be used to compare OS between the 4 treatment arms.
- Incidence of toxicity [ Time Frame: Up to 3 years ]Will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Toxicity defined as any grade 3 or 4 non-hematologic toxicity.
- MET mutation rate [ Time Frame: Up to 3 years ]The hazard ratio between the MET inhibitor versus (vs.) sunitinib in those with versus without the mutation (i.e., the interaction) will be compared. Response Evaluation Criteria in Solid Tumors (RECIST) response rate (confirmed and unconfirmed partial response and complete response) based on MET mutation/expression level will be compared using the chi-square test.
- Assessment of type I and type II renal papillary cancer [ Time Frame: Up to 3 years ]Will be assessed per RECIST 1.1 criteria. The study will pool the three met inhibitor arms and will evaluate the response to these treatments by type I vs. II status. Will primarily look at RECIST response, but will also look at PFS. The study will also describe the response rate and PFS estimates for type I and II for the sunitinib arm along with 95% confidence intervals.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02761057
|Principal Investigator:||Sumanta K Pal||Southwest Oncology Group|