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Digestive System Diseases

Adenocarcinoma

Colorectal Neoplasms

Intestinal Neoplasms

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Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Oxaliplatin

Bevacizumab

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Everolimus

Immunoglobulins

Sirolimus

Temsirolimus

MTOR Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

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Immunologic Factors

Everolimus was supplied in 5 mg tablets in blister packs.

Everolimus (RAD001)

Novartis Pharmaceuticals

To assess the safety and efficacy of weekly (70 mg per week) and daily (10 mg per day) everolimus in patients with metastatic colorectal cancer whose cancer has progressed despite prior treatment with targeted therapy and chemotherapy.

Efficacy and Safety of Everolimus in Patients With Metastatic Colorectal Cancer Who Have Failed Prior Targeted Therapy and Chemotherapy

A Single Arm, Multicenter Phase II Study of Everolimus in Patients With Metastatic Colorectal Adenocarcinoma Whose Cancer Has Progressed Despite Prior Therapy With an Anti-EGFR Antibody (if Appropriate), Bevacizumab, Fluoropyrimidine, Oxaliplatin, and Irinotecan-based Regimens

RECIST (Response Evaluation Criteria In Solid Tumors) is a set of published rules that define when cancer patients improve ("respond"), stay the same ("stable") or worsen ("progression") during treatments.

Disease Control Rate (DCR) defined as the percentage of participants with Disease Control best overall response (complete response, partial response or stable disease)and Objective Response Rate (ORR) defined as the percentage of participants with best overall Objective Response (complete response or partial response).

RECIST (Response Evaluation Criteria In Solid Tumors) is a set of published rules that define when cancer patients improve ("respond"), stay the same ("stable") or worsen ("progression") during treatments.

Best Over Response (BOR): Complete Response (CR, No lesions), Partial Response (PR, 30% decrease in lesions), and Stable Disease (SD, none of the above)

Duration in months from the date of first study treatment to the date of the first documented disease progression or death due to any cause.

Overall survival defined as the time from date of first study treatment to the date of death due to any cause.

Toxicity assessed using the NIH-NCI Common Terminology Criteria for Adverse Events, Version 3.0 (CTCAEv3.0). On treatment death defined as deaths occurring no more than 28 days after the discontinuation of study treatment.

The efficacy variable compared in this biomarker analysis is disease control rate (DCR) within the 70mg/week arm in the analysis not adjusted for prognostic factors: from archival tumor tissue (and additionally from a biopsy at a metastatic site, if available), collected during screening: KRAS gene mutation. From blood plasma, collected at screening then on day 1 at cycles 2, 3 and 4, and at the end of treatment: blood lactate dehydrogenase (LDH) isoenzyme fractionation and serum levels of sVEGFR2, bFGF, PLGF and VEGF.

The efficacy variable compared in this biomarker analysis is disease control rate (DCR) within the 10mg/day arm in the analysis not adjusted for prognostic factors: from archival tumor tissue (and additionally from a biopsy at a metastatic site, if available), collected during screening: KRAS gene mutation. From blood plasma, collected at screening then on day 1 at cycles 2, 3 and 4, and at the end of treatment: blood lactate dehydrogenase (LDH) isoenzyme fractionation and serum levels of sVEGFR2, bFGF, PLGF and VEGF.

The efficacy variable that was compared in the biomarker analysis are Median progression free survival (PFS) and overall survival (OS) within the Everolimus (RAD001) 70mg/week arm in the analysis not adjusted for prognostic factors: from archival tumor tissue (and additionally from a biopsy at a metastatic site, if available), collected during screening: KRAS gene mutation. From blood plasma, collected at screening then on day 1 at cycles 2, 3 and 4, and at the end of treatment: blood lactate dehydrogenase (LDH) isoenzyme fractionation and serum levels of sVEGFR2, bFGF, PLGF and VEGF.

The efficacy variable that was compared in the biomarker analysis are Median progression free survival (PFS) and overall survival (OS) within the Everolimus (RAD001) 10mg/day arm in the analysis not adjusted for prognostic factors: from archival tumor tissue (and additionally from a biopsy at a metastatic site, if available), collected during screening: KRAS gene mutation. From blood plasma, collected at screening then on day 1 at cycles 2, 3 and 4, and at the end of treatment: blood lactate dehydrogenase (LDH) isoenzyme fractionation and serum levels of sVEGFR2, bFGF, PLGF and VEGF.

The efficacy variable that was compared in the biomarker analysis is DCR within the Everolimus (RAD001) 70mg/week arm in the analysis not adjusted for prognostic factors: from archival tumor tissue (and additionally from a biopsy at a metastatic site, if available), collected during screening: PTEN loss (imunohistochemistry, IHC), phosphoAKT (IHC), phosphoS6 (IHC), and p53 (IHC). From blood plasma, collected at screening then on day 1 at cycles 2, 3 and 4, and at the end of treatment: blood lactate dehydrogenase (LDH) isoenzyme fractionation and serum levels of sVEGFR2, bFGF, PLGF and VEGF.

The efficacy variable that was compared in the biomarker analysis is DCR within the Everolimus (RAD001) 10mg/day arm in the analysis not adjusted for prognostic factors: from archival tumor tissue (and additionally from a biopsy at a metastatic site, if available), collected during screening: PTEN loss (imunohistochemistry, IHC), phosphoAKT (IHC), phosphoS6 (IHC), and p53 (IHC). From blood plasma, collected at screening then on day 1 at cycles 2, 3 and 4, and at the end of treatment: blood lactate dehydrogenase (LDH) isoenzyme fractionation and serum levels of sVEGFR2, bFGF, PLGF and VEGF.

The efficacy variable that was compared in the biomarker analysis are PFS \& OS within the Everolimus (RAD001) 70mg/Week arm in the analysis not adjusted for prognostic factors: from archival tumor tissue (and additionally from a biopsy at a metastatic site, if available), collected during screening: PTEN loss (imunohistochemistry, IHC), phosphoAKT (IHC), phosphoS6 (IHC), and p53 (IHC). From blood plasma, collected at screening then on day 1 at cycles 2, 3 and 4, and at the end of treatment: blood lactate dehydrogenase (LDH) isoenzyme fractionation and serum levels of sVEGFR2, bFGF, PLGF and VEGF.

The efficacy variable that was compared in the biomarker analysis are PFS \& OS within the Everolimus (RAD001) 10mg/day arm in the analysis not adjusted for prognostic factors: from archival tumor tissue (and additionally from a biopsy at a metastatic site, if available), collected during screening: PTEN loss (imunohistochemistry, IHC), phosphoAKT (IHC), phosphoS6 (IHC), and p53 (IHC). From blood plasma, collected at screening then on day 1 at cycles 2, 3 and 4, and at the end of treatment: blood lactate dehydrogenase (LDH) isoenzyme fractionation and serum levels of sVEGFR2, bFGF, PLGF and VEGF.

Participants self-administered weekly oral dose of Everolimus (RAD001). Drug supplied as 5 mg tablets in blister packs.

Everolimus (RAD001) 70 mg/Week

Participants self-administered daily oral dose of Everolimus (RAD001). Drug supplied as 5 mg tablets in blister packs.

Everolimus (RAD001) 10 mg/Day

Total

Age, Continuous

<45 Years

45 to <55 Years

55 to <65 Years

> or = to 65 Years

Age, Customized

Sex: Female, Male

Study Director

Disease Control Rate (DCR)

Objective Response Rate (ORR)

Disease Control Rate (DCR) and Objective Response Rate (ORR) According to the Response Evaluation Criteria in Solid Tumors (RECIST)

Complete Response (CR)

Partial Response (PR)

Stable Disease (SD)

Progressive Disease (PD)

Disease Control (CR or PR or SD)

Objective Response (CR or PR)

Unknown

The Number of Participants With Best Overall Response According to Response Evaluation Criteria in Solid Tumors (RECIST)

Progression- Free Survival (PFS) was analyzed in Full Analysis Set \[FAS\].

Progression-free Survival (PFS)

Overall Survival \[OS\] was analyzed in Full Analysis Set \[FAS\].

Overall Survival (OS)

Deaths

On-treatment Death

SAE regardless of relationship to study treatment

SAE with suspected relationship to study treatment

AE Grade 3-4, regardless of relationship to study

AE Grade 3-4, suspected relationship to study tr

AE leading to discontinuation

Clinically notable adverse event

Number of Patients Who Died, Had an Serious Adverse Event (SAE), Had Grade 3 to 4 Adverse Event (AE), Discontinued Due to an AE, or Had a Clinical Notable AE by Treatment (tr).

KRAS Mutation/Everolimus (RAD001) 70 mg/Week

Participants self-administered daily oral dose of Everolimus (RAD001). Drug supplied as 5 mg tablets in blister packs

KRAS Wildtype/Everolimus (RAD001) 70 mg/Week

Biomarker Predictive of Clinical Benefit (DCR by KRAS) on Everolimus (RAD001) 70 mg/Week

KRAS Mutation/Everolimus (RAD001) 10 mg/Day

KRAS Wildtype/Everolimus (RAD001) 10 mg/Day

Biomarker Predictive of Clinical Benefit (DCR by KRAS) on Everolimus (RAD001) 10 mg/Day

Median PFS

Median OS

Biomarkers Predictive of Clinical Benefit (Median PFS and OS by KRAS ) on Everolimus (RAD001) 70mg/Week

Biomarkers Predictive of Clinical Benefit (Median PFS and OS by KRAS) on Everolimus (RAD001) 10mg/Day

PTEN Expression Low/Everolimus (RAD001) 70 mg/Week

PTEN Expression Normal/Everolimus (RAD001) 70 mg/Week

Biomarkers Predictive of Clinical Benefit (DCR by PTEN ) on Everolimus (RAD001) 70mg/Week

PTEN Expression Low/Everolimus (RAD001) 10 mg/Day

PTEN Expression Normal/Everolimus (RAD001) 10 mg/Day

Biomarkers Predictive of Clinical Benefit (DCR by PTEN ) on Everolimus (RAD001) 10mg/Day

Biomarkers Predictive of Clinical Benefit (Median PFS and OS by PTEN ) on Everolimus (RAD001) 70mg/Week

Biomarkers Predictive of Clinical Benefit (Median PFS and OS by PTEN ) on Everolimus (RAD001) 10mg/Day

Overall Study

Spots Global Cancer Trial Database for Efficacy and Safety of Everolimus in Patients With Metastatic Colorectal Cancer Who Have Failed Prior Targeted Therapy and Chemotherapy

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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