Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Carcinoma

Carcinoma, Renal Cell

Kidney Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Everolimus

Sunitinib

Sirolimus

Temsirolimus

MTOR Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Immunosuppressive Agents

Immunologic Factors

Angiogenesis Inhibitors

Growth Inhibitors

Subjects in this treatment arm will receive everolimus/RAD001 10 mg orally once daily by mouth on days 1 through 42 for each 42 day cycle.

Subjects in this treatment arm will take sunitinib 50 mg daily by mouth on days 1 through 28 of each 42 day cycle.

Subjects in this treatment arm will receive everolimusRAD001 10 mg orally once daily by mouth on days 1 through 42 for each 42 day cycle.

50 mg daily by mouth on days 1 through 28 of each 42 day cycle.

Andrew Armstrong, MD, ScM

To compare the anti-tumor activity of everolimus and sunitinib in subjects with metastatic renal cell carcinoma (mRCC) with non-clear cell pathology.

This will be an international (USA, Canada, and UK) open-label, outpatient, multicenter, randomized study of treatment with RAD001 (everolimus (Afinitor®) or sunitinib (Sutent®) in subjects with mRCC and non-clear cell histology. Special emphasis is placed on papillary and chromophobe histologies while sarcomatoid clear cell variants, medullary, and collecting duct carcinomas will be excluded (see eligibility). Subjects may continue receiving study drugs until disease progression, unacceptable toxicities, or withdrawal of consent, for a maximum of 24 months. Continuation of study assigned treatment will be allowed beyond 24 months at the discretion of the sponsor. Stratification variables will include histology (papillary vs. chromophobe) and Motzer risk criteria (0, 1-2, and 3). Tumor progression will be assessed locally and by independent review, in strict accordance with Response Evaluation Criteria in Solid Tumors (RECIST 1.1) criteria measured every 12 weeks. At the time of progression, subjects will be taken off study other than simple administrative mortality follow-up. Primary pathologic samples and plasma/urine angiokine levels at baseline and over time will be collected and stored centrally for biomarker analysis.

Phase II Study of Afinitor vs. Sutent in Patients With Metastatic Non-Clear Cell Renal Cell Carcinoma

A Randomized Phase II Study of Afinitor (RAD001) vs. Sutent (Sunitinib) in Patients With Metastatic Non-Clear Cell Renal Cell Carcinoma (ASPEN)

To correlate clinical measures of response and PFS with baseline and time-dependent levels of biomarkers. These biomarkers include plasma angiokine levels, tissue immunohistochemical and genomic profiles, copy number as assessed by array-based comparative genomic hybridization (CGH), and known mutations in non-clear cell RCC

To evaluate in an exploratory fashion changes in copy number, RNA expression, and immunohistochemical profiles by microarray between primary non-clear cell RCC tumors and metastatic samples

The primary objective will be to compare the anti-tumor activity of everolimus and sunitinib in subjects with mRCC with non-clear cell pathology, as measured by progression-free survival (PFS) following treatment initiation according to RECIST 1.1 criteria. Progressive disease is defined as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. 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).

6-, 12-, and 24-month rates of PFS in each arm will be compared for each treatment arm. Progressive disease is defined as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. 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).

Progression-free survival (PFS) expressed in months as compared to an historic control (interferon-treated clear cell RCC control arm from the sunitinib phase III study). Progressive disease is defined as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. 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).

Defined as complete response \[CR\] and partial response \[PR\] by RECIST 1.1 criteria in each treatment arm.Overall Response Rate (ORR) = CR + PR. Complete Response (CR) is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response (PR) is at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Percentage of participants with stable disease during treatment is defined as stable disease \[SD\] by RECIST 1.1 criteria as calculated in each treatment arm. Stable Disease (SD) is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

Rate of complete or partial response or stable disease by the RECIST 1.1 criteria lasting ≥ 12 weeks prior to progression. Benefit rate is defined as complete response \[CR\] and partial response \[PR\] and stable disease \[SD\] by RECIST 1.1 criteria in each treatment arm. Benefit rate = CR + PR + SD. Complete Response (CR) is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response (PR) is at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

To compare overall survival (OS) rates at 6, 12, 24, and 36 months and over time in each treatment arm.

To compare the best tumor shrinkage as a percentile in each treatment arm. The percentile change at each follow up visit is calculated by measuring the percentage change in the Sum of lesion measurement from baseline. The best tumor shrinkage is lowest percentile change. A decrease is indicated by a negative percentage.

To compare the median duration of response (CR, PR, and SD) in each treatment arm. According to RECIST 1.1, Complete Response (CR) is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response (PR) is at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

To compare the median OS in each treatment arm.

To compare the time-to-new metastatic disease in each treatment arm, defined from the date of first study agent administration to the onset of a new evaluable site of disease, excluding the primary site and all sites documented at baseline

To assess toxicities associated with everolimus or sunitinib using NCI CTC version 4.0 criteria

To compare change in quality-of-life, as measured by the FACT-KSI scale at baseline and cycle 3 day 1 per subject in each treatment arm. Functional Assessment of Cancer Therapy Kidney Symptom Index. FKSI is a questionnaire for FACT-Kidney Symptom Index used to assess QoL/participant-reported outcomes for participants diagnosed with renal cell cancer. The FKSI contained 15 questions each ranging from 0 (not at all) to 4 (very much) so that FKSI ranged between 0-60 where higher scores reflects better functioning and fewer symptoms.

To compare change in quality-of-life, as measured by the FACT-KSI scale at baseline and cycle 6 day1 per subject in each treatment arm. Functional Assessment of Cancer Therapy Kidney Symptom Index. FKSI is a questionnaire for FACT-Kidney Symptom Index used to assess QoL/participant-reported outcomes for participants diagnosed with renal cell cancer. The FKSI contained 15 questions each ranging from 0 (not at all) to 4 (very much) so that FKSI ranged between 0-60 where higher scores reflects better functioning and fewer symptoms.

To compare change in quality-of-life, as measured by the FACT-KSI scale at baseline and end of treatment per subject in each treatment arm. Functional Assessment of Cancer Therapy Kidney Symptom Index. FKSI is a questionnaire for FACT-Kidney Symptom Index used to assess QoL/participant-reported outcomes for participants diagnosed with renal cell cancer. The FKSI contained 15 questions each ranging from 0 (not at all) to 4 (very much) so that FKSI ranged between 0-60 where higher scores reflects better functioning and fewer symptoms.

Novartis

Pfizer

Duke University

Subjects in this treatment arm will receive everolimus/RAD001 10 mg orally once daily by mouth on days 1 through 42 for each 42 day cycle.

Everolimus: Subjects in this treatment arm will receive everolimusRAD001 10 mg orally once daily by mouth on days 1 through 42 for each 42 day cycle.

RAD001

Subjects in this treatment arm will take sunitinib 50 mg daily by mouth on days 1 through 28 of each 42 day cycle.

Sunitinib: 50 mg daily by mouth on days 1 through 28 of each 42 day cycle.

Total

Age, Continuous

Sex: Female, Male

Dr. Andrew J Armstrong

Anti-tumor Activity as Measured by Median Progression Free Survival Time

6 Months

12 Months

24 Months

Progression Free Survival Rates

A comparison of the median PFS for RAD001 arm was compared to the 95% confidence interval(CI) of the median PFS of the historical control (HC). The null hypothesis was that there is no difference in the median PFS between the treatment arms and the historical control. If the median PFS is outside the 95%CI for the HC,it is determined there is statistical evidence that median PFS is different from the HC.

A comparison of the median PFS for Sunitinib arm was compared to the 95% confidence interval(CI) of the median PFS of the historical control (HC). The null hypothesis was that there is no difference in the median PFS between the treatment arms and the historical control. If the median PFS is outside the 95%CI for the HC,it is determined there is statistical evidence that median PFS is different from the HC.

PFS Expressed in Months

Overall Response Rate

Percentage of Participants With Stable Disease (SD)

12 Week Clinical Benefit Rate as Percentage

6 months

12 months

24 months

36 months

Overall Survival Rates

Best Tumor Shrinkage as a Percentile in Each Arm

Median Duration of Response (CR, PR, and SD)

Median OS

Time-to-new Metastatic Disease in Each Treatment Arm

Percentage of Participants With Adverse Events

All participants who completed the cycle 3 day 1 visit.

Change in Quality-of-life

All participants who completed the cycle 6 day 1 visit.

All participants who completed the End of treatment visit.

Spots Global Cancer Trial Database for chromophobe renal cell