Temsirolimus Versus Sorafenib As Second-Line Therapy In Patients With Advanced RCC Who Have Failed First-Line Sunitinib

Pfizer512 enrolled

Overview

This is an international, randomized, open-label, outpatient, multicenter study. Subjects will be assigned in a 1:1 ratio to 1 of 2 treatment arms: temsirolimus 25 mg once weekly by intravenous (IV) infusion or sorafenib 400 mg by mouth (PO) twice daily (BID). These investigational drugs will be administered in 6-week cycles for the duration of the study, up to 24 months. Subjects will be stratified by nephrectomy status, duration of response to sunitinib therapy, Memorial Sloan Kettering Cancer Center (MSKCC) prognostic group, and RCC tumor histology.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

512

Conditions

Renal Cell Carcinoma

Interventions

Sorafenib

temsirolimus (Torisel)DRUG

Subjects randomized to arm A will receive temsirolimus (Torisel) 25 mg via IV infusion once weekly. This infusion is to be administered over a 30-60 minute period. Subjects are to be pre-treated with 25-50 mg IV diphenhydramine (or comparable IV antihistamine) approximately 30 minutes before temsirolimus infusion.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Histologically confirmed diagnosis of mRCC (regardless of histology or nephrectomy status) with well-documented Radiological PD by RECIST criteria or clinical PD as judged by the investigator while receiving first-line sunitinib therapy. Subjects must have at least 1 cycle of sunitinib therapy (minimum of four weeks continuously). * At time of randomization, at least 2 weeks since prior treatment with sunitinib, palliative radiation therapy, and/or surgery. * At time of randomization, there must be at least 1 measurable lesion per RECIST. Lesions that have been previously irradiated or embolized cannot be selected as target lesions. * More criteria apply Exclusion Criteria: * Metastatic CNS from RCC. * Subjects who discontinued Sutent therapy due specifically to intolerance. * Prior systemic therapy for mRCC other than sunitinib. * Active ketonuria, secondary to poorly controlled diabetes mellitus * More criteria apply

Locations (128)

Pfizer Investigational Site

Duarte, California, United States

Pfizer Investigational Site

La Jolla, California, United States

Pfizer Investigational Site

La Jolla, California, United States

Pfizer Investigational Site

Los Angeles, California, United States

Pfizer Investigational Site

Los Angeles, California, United States

Outcomes

Primary Outcomes

Progression-Free Survival (PFS)

Interval from date of randomization until documentation of progressive disease (PD) by an independent tumor assessment according to Response Evaluation Criteria in Solid Tumor (RECIST) or death for any reason whichever occurred first.

Time frame: Baseline up to 24 Months

Secondary Outcomes

Progression Free Survival (PFS) by Investigator Assessment

Interval from date of randomization until documentation of PD by an investigator tumor assessment, symptomatic deterioration, or death for any reason whichever occurred first.

Time frame: Baseline up to 24 Months

Percentage of Participants With Tumor Response

Percentage of participants with tumor response based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST and evaluated by independent central review. CR/PR persisted on repeat imaging study at least 4 weeks after initial documentation of response. PR had at least 30 percent decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD.

Time frame: Baseline up to 24 Months

Overall Survival (OS)

Overall survival was the duration from randomization to death. For participants who are alive, overall survival was censored at the last contact.

Time frame: Baseline to date of death from any cause (up to 24 months)

Percentage of Participants With PFS Events at 12, 24 and 36 Weeks by Independent Assessment

PFS: Interval from date of randomization until documentation of PD by an independent tumor assessment according to RECIST or death for any reason whichever occurred first. PFS calculated as (Weeks)=(randomization date minus first dose date plus 1) divided by 7.

Time frame: Weeks 12, 24, and 36

Duration of Response (DR)

Duration of response as defined by the time from CR or PR (whichever status recorded first) until the date of death or PD was objectively documented. Median and its 95 percent confidence interval (95% CI) were estimated using Kaplan-Meier method.

Time frame: Baseline up to 24 Months