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Phase II Study of Single Agent RAD001 in Patients With Colon Cancer and Activating Mutations in the PI3KCA Gene

Phase 2
18 Years
Not Enrolling
Colorectal Cancer

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Trial Information

Phase II Study of Single Agent RAD001 in Patients With Colon Cancer and Activating Mutations in the PI3KCA Gene


- 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.

Inclusion Criteria


- 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

- 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

- 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

Type of Study:


Study Design:

Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Response rate

Principal Investigator

Manuel Hidalgo, MD, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Sidney Kimmel Comprehensive Cancer Center



Study ID:




Start Date:

October 2006

Completion Date:

Related Keywords:

  • Colorectal Cancer
  • 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
  • Colonic Neoplasms
  • Colorectal Neoplasms



Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Baltimore, Maryland  21231-2410