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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00419159
First received: January 4, 2007
Last updated: November 4, 2011
Last verified: November 2011
  Purpose

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 Intervention Phase
Colorectal Cancer
Drug: Everolimus (RAD001)
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

    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).


  • 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 ] [ Designated as safety issue: No ]
    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:
  • Progression-free Survival (PFS) [ Time Frame: Imaging every 8 weeks ] [ Designated as safety issue: No ]
    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 (OS) [ Time Frame: Every 3 months ] [ Designated as safety issue: No ]
    Overall survival defined as the time from date of first study treatment to the date of death due to any cause.

  • 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 ] [ Designated as safety issue: Yes ]
    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.

  • Biomarkers Predictive of Clinical Benefit on Everolimus (RAD001) [ Time Frame: Screening and Day 1 of cycles 2, 3, 4 and end of treatment ] [ Designated as safety issue: No ]

Enrollment: 199
Study Start Date: December 2006
Study Completion Date: March 2009
Primary Completion Date: March 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00419159

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

Additional Information:
No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00419159     History of Changes
Other Study ID Numbers: CRAD001C2241
Study First Received: January 4, 2007
Results First Received: December 17, 2010
Last Updated: November 4, 2011
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
Italy: Ministry of Health
Spain: Spanish Agency of Medicines

Keywords provided by Novartis:
Colorectal cancer
metastatic colorectal adenocarcinoma
anti-EGFR antibody

Additional relevant MeSH terms:
Adenocarcinoma
Colorectal Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Everolimus
Sirolimus
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Antifungal Agents
Anti-Infective Agents
Anti-Bacterial Agents

ClinicalTrials.gov processed this record on July 08, 2014