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

Study Description

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Colorectal Cancer	Drug: Everolimus (RAD001)	Phase 2

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	199 participants
Allocation:	Non-Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	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
Study Start Date :	December 2006
Actual Primary Completion Date :	March 2009
Actual Study Completion Date :	March 2009

Arms and Interventions

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Arm	Intervention/treatment
Experimental: Everolimus (RAD001) 70 mg/week	Drug: Everolimus (RAD001); Everolimus was supplied in 5 mg tablets in blister packs.; Other Names: Afinitor; Zortress; Certican
Experimental: Everolimus (RAD001) 10 mg/day	Drug: Everolimus (RAD001); Everolimus was supplied in 5 mg tablets in blister packs.; Other Names: Afinitor; Zortress; Certican

Outcome Measures

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Primary Outcome Measures :

1. Disease Control Rate (DCR) and Objective Response Rate (ORR) According to the Response Evaluation Criteria in Solid Tumors (RECIST) [ Time Frame: Imaging every 8 weeks ]

   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).

2. The Number of Participants With Best Overall Response: Complete Response (CR, No Lesions), Partial Response (PR, 30% Decrease in Lesions), and Stable Disease (SD, None of the Above) According to Response Evaluation Criteria in Solid Tumors (RECIST) [ Time Frame: Imaging every 8 weeks ]
   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.

Secondary Outcome Measures :

1. Progression-free Survival (PFS) [ Time Frame: Imaging every 8 weeks ]
   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.
2. Overall Survival (OS) [ Time Frame: Every 3 months ]
   Overall survival defined as the time from date of first study treatment to the date of death due to any cause.
3. 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). [ Time Frame: From the first day of treatment until 28 days after discontinuation of study treatment ]
   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.
4. Biomarkers Predictive of Clinical Benefit on Everolimus (RAD001) [ Time Frame: Screening and Day 1 of cycles 2, 3, 4 and end of treatment ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion criteria:

• Age ≥ 18 years old.
• Patients with metastatic colorectal cancer (CRC).
• Patients must have sufficient and obtainable tumor tissue for biomarker analysis from original surgical resection.
• Patients with documented disease progression within 6 months of their most recent dose of chemotherapeutic regimens.
• Patients with at least one measurable lesion.
• Adequate bone marrow function.
• Adequate liver function.
• Adequate renal function.
• Patients with a life expectancy of > 3 months.
• Patients with a World Health Organization (WHO) performance status of 0, 1, or 2.
• Women of childbearing potential must have had a negative serum pregnancy test 72 hours prior to the administration of the first study treatment.
• Patients who give a written informed consent obtained according to local guidelines.

Exclusion criteria:

• Patients currently receiving anti-cancer agents or who have received these within 4 weeks prior to study entry.
• Patients who have previously received RAD001.
• Patients with a known hypersensitivity to everolimus or other rapamycins (sirolimus, temsirolimus) or to its excipients.
• Chronic treatment with steroids or another immunosuppressive agent.
• Patients with untreated central nervous system (CNS) metastases or neurologically unstable CNS metastases.
• HIV seropositivity.
• Patients with an active, bleeding diathesis. Patients may use enoxaparin.
• Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study.
• Patients who have a history of another primary malignancy < 3 years, with the exceptions of non-melanoma skin cancer, and carcinoma in situ of uterine cervix.
• Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods.
• Patients who are using other investigational agents or who had received investigational drugs ≤ 4 weeks prior to first study treatment.
• Patients unwilling to or unable to comply with the protocol.

Other protocol defined inclusion/exclusion criteria may apply

Contacts and Locations

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Locations

United States, Nevada
Nevada Cancer Institute
Las Vegas, Nevada, United States, 89135

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

Study Director:	Novartis Pharmaceuticals	Novartis Pharmaceuticals

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Additional Information:

Visit NovartisClinicalTrials.com: Pre-qualify for a trial, and view a list of trials and participating study centers. 

Responsible Party:	Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT00419159 History of Changes
Other Study ID Numbers:	CRAD001C2241
First Posted:	January 8, 2007
Results First Posted:	May 16, 2011
Last Update Posted:	November 16, 2011
Last Verified:	November 2011

Keywords provided by Novartis ( Novartis Pharmaceuticals ):

Colorectal cancer; metastatic colorectal adenocarcinoma; anti-EGFR antibody

Additional relevant MeSH terms:

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases	Everolimus; Sirolimus; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Anti-Bacterial Agents; Anti-Infective Agents; Antibiotics, Antineoplastic; Antifungal Agents