Everolimus in Treating Patients With Advanced or Metastatic Colorectal Cancer That Did Not Respond to Previous Therapy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00390364
Recruitment Status : Terminated (Withdrawn due to low accrual)
First Posted : October 19, 2006
Results First Posted : October 8, 2014
Last Update Posted : October 8, 2014
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center

Brief Summary:

RATIONALE: Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.

PURPOSE: This phase II trial is studying how well everolimus works in treating patients with advanced or metastatic colorectal cancer that did not respond to previous therapy.

Condition or disease Intervention/treatment Phase
Colorectal Cancer Drug: everolimus Procedure: antiangiogenesis therapy Procedure: biopsy Procedure: diagnostic procedure Procedure: gene expression analysis Procedure: immunohistochemistry staining method Procedure: laboratory biomarker analysis Procedure: mutation analysis Procedure: protein tyrosine kinase inhibitor therapy Procedure: reverse transcriptase-polymerase chain reaction Phase 2

Detailed Description:


  • Determine response rate, time to tumor progression, and survival of patients with advanced or metastatic refractory colorectal cancer and mutations in the PI3K gene treated with everolimus.
  • Determine the toxicity profile of this drug in these patients.
  • Measure the signaling pathways activated in these patients.
  • Determine the pharmacodynamic effects of this drug in these patients.

OUTLINE: This is an open-label study.

Patients receive oral everolimus once daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Patients undergo tumor biopsies and normal skin biopsies at baseline and after the first course of study treatment. Tumor tissue is examined for biological markers (e.g., epidermal growth factor receptor, ERK, Akt, p70s6k, p27, and Rb protein) by immunohistochemistry; apoptosis quantification by TUNEL assay; Ki-67 quantification and Ki-index; gene expression; and c-fos and p27 expression by reverse-transcriptase polymerase chain reaction.

PROJECTED ACCRUAL: A total of 37 patients will be accrued for this study.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Study of Single Agent RAD001 in Patients With Colon Cancer and Activating Mutations in the PI3KCA Gene
Study Start Date : October 2006
Primary Completion Date : October 2007
Study Completion Date : October 2007

Resource links provided by the National Library of Medicine

Drug Information available for: Everolimus
U.S. FDA Resources

Primary Outcome Measures :
  1. Response Rate: The Total Number of Participants With Progression of Disease [ Time Frame: 1 month ]

    To determine response rate and time to tumor progression of patients with colorectal cancer and mutations in the PI3KCA gene who are treated with RAD001. Response and progression will be evaluated in this study using the international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee.

    Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions assessed by CT (or MRI): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesion. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesion.

    The outcome measure will be the total number of subjects who show progression of disease.

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


  • Cytologically or pathologically confirmed colorectal adenocarcinoma

    • Advanced or metastatic disease
  • Refractory to ≥ 1 line of prior therapy

    • Not amenable to potentially curative surgical resection
  • Mutations in the PI3K gene in tumor tissue
  • Tumor tissue available for genetic testing OR willing to undergo baseline tumor biopsy

    • Tumor amenable to sequential biopsies
    • Willing to undergo 2 sequential tumor biopsies, and 2 sequential skin biopsies
  • Measurable lesion with ≥ 1 diameter ≥ 2 cm by conventional CT scan (1 cm by spiral CT scan) in a nonirradiated area
  • No known brain metastases


  • ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
  • Life expectancy > 12 weeks
  • WBC ≥ 3,000/mm³
  • Absolute neutrophil count ≥ 1,500/mm³
  • Platelet count ≥ 100,000/mm³
  • Bilirubin normal
  • AST and ALT ≤ 2.5 times upper limit of normal (ULN)
  • Creatinine normal OR creatinine clearance ≥ 60 mL/min
  • Cholesterol and triglycerides ≤ 2.5 times ULN
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No history of allergic reactions attributed to compounds of similar chemical or biologic composition to everolimus
  • No uncontrolled intercurrent illness, including, but not limited to, any of the following:

    • Hypertension
    • Ongoing or active infection
    • Symptomatic congestive heart failure
    • Unstable angina pectoris
    • Cardiac arrhythmia
    • Psychiatric illness or social situation that would preclude study compliance
  • No evidence of bleeding diathesis
  • Able to swallow tablets


  • See Disease Characteristics
  • At least 4 weeks since prior radiotherapy or chemotherapy (6 weeks for nitrosoureas or mitomycin C) and recovered
  • No prior targeted therapy against mTOR
  • No other concurrent investigational agents
  • No concurrent therapeutic anticoagulation

    • Prophylactic anticoagulation (i.e., low-dose warfarin) of venous or arterial access devices allowed provided the requirements for PT, INR or PTT are met.
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  • No other concurrent anticancer therapy, including chemotherapy, hormonal therapy, immunotherapy, alternative therapy, or radiotherapy
  • No concurrent live vaccination

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00390364

United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21231-2410
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center
National Cancer Institute (NCI)
Principal Investigator: Manuel Hidalgo, MD, PhD Sidney Kimmel Comprehensive Cancer Center

Responsible Party: Sidney Kimmel Comprehensive Cancer Center Identifier: NCT00390364     History of Changes
Other Study ID Numbers: J05107 CDR0000508071
First Posted: October 19, 2006    Key Record Dates
Results First Posted: October 8, 2014
Last Update Posted: October 8, 2014
Last Verified: October 2014

Keywords provided by Sidney Kimmel Comprehensive Cancer Center:
adenocarcinoma of the colon
adenocarcinoma of the rectum
recurrent colon cancer
stage III colon cancer
stage IV colon cancer
recurrent rectal cancer
stage III rectal cancer
stage IV rectal cancer

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents