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Everolimus/Sorafenib or Sunitinib in Patients With Metastatic Renal Cell Carcinoma (RCC)

Phase 2
Withdrawn
Conditions
Locally Metastatic Malignant Neoplasm
Interventions
Registration Number
NCT01616186
Lead Sponsor
Andrea Harzstark
Brief Summary

This is a phase II trial that follows the completion of the phase I UCSF trial of everolimus and sorafenib for Renal Cell Carcinoma (RCC). This trial will be for patients who have not had treatment for RCC before. This trial will have 2/3 patients getting everolimus/sorafenib treatment and 1/3 getting sunitinib, an FDA approved RCC drug. All three drugs are approved for advanced RCC when used individually, the combination of everolimus and sorafenib for RCC is not approved by the FDA.

Detailed Description

In the phase I study of the combination of everolimus and sorafenib, clinical benefit was observed in patients with no prior systemic therapy. There was no evidence of pharmacokinetic interaction and acceptable toxicity at a dosage of sorafenib of 400 mg twice daily (BID) and everolimus 5 mg daily. Based on these data and the need for more effective front-line therapy for renal cell carcinoma, the plan is to investigate this regimen in patients who have not undergone prior therapy. A sunitinib arm is being included as a concurrent reference to help provide a guideline of an activity level and toxicity that would be meaningful to move forward to a phase III study. Therefore, this study is designed as a non-comparative investigation and patients will be randomized in a 2:1 ratio to everolimus/sorafenib or to sunitinib, respectively.

Recruitment & Eligibility

Status
WITHDRAWN
Sex
All
Target Recruitment
Not specified
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Everolimus/SorafenibEverolimus and sorafenibPatients will be stratified by current smoking status (smoker: yes or no0, for each smoking stratum patients will be randomized in a 2:1 ratio
SunitinibSunitinib monotherapy* Sunitinib is the concurrent control group * Patients will be stratified by current smoking status (smoker: yes or no), for each smoking stratum patients will be randomized in a 2:1 ratio
Primary Outcome Measures
NameTimeMethod
Objective response12-18 weeks

Computerized Tomography Scans (CT) done at Screening and every 2 cycles

* For Partial Response (PR) or Complete Response (CR), changes in tumor measurements must be confirmed by repeat studies no less than 4 weeks after the criteria for response are first met (RECIST 1.1 criteria)

* For Stable Disease (SD), follow-up measurements must have met the SD criteria at least once after study entry at a minimum of 12 weeks after study entry

Secondary Outcome Measures
NameTimeMethod
Safety: combination of everolimus and sorafenib12-18 weeks

Safety/Adverse Event (AE) assessments done on Day 1, 21, 42 during Cycle 1 \& Day 28 of all subsuquent cycles; assessments include Eastern Oncology Group Conference (ECOG) Performance scale, physical/history, hematology \& chemistry labs; other safety data (e.g. Electrocardiogram \[ECG\], Multigated Acquisition Scan \[MUGA\], etc.) will be considered as appropriate

Progression-free Survival (PFS)12-18 weeks

- PFS will be measured (using RECIST 1.1 criteria) from the start of protocol therapy until the date of the first occurrence of recurrent or progressive disease or death

Time-to-Progression (TTP)12-18 weeks

- TTP will be measured from the start of protocol therapy until first date that recurrent or progressive disease is documented

Clinical Benefit rate12-18 weeks

Clinical benefit (defined as objective response+stable disease) will be summarized for each treatment arm by the proportion of patients achieving this outcome with 95% confidence intervals

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