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

Colorectal Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00390364
• Other study ID #: J05107 CDR0000508071
• Secondary ID: JHOC-J05107NOVAR
• Status: Terminated
• Phase: Phase 2
• First received: October 18, 2006
• Last updated: October 7, 2014
• Start date: October 2006
• Est. completion date: October 2007

Study information

• Verified date: October 2014
• Source: Sidney Kimmel Comprehensive Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Description:

OBJECTIVES:

• 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1
• Est. completion date: October 2007
• Est. primary completion date: October 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

DISEASE CHARACTERISTICS:

• 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

PATIENT CHARACTERISTICS:

• 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

PRIOR CONCURRENT THERAPY:

• 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

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms

Intervention

Drug:
• everolimus

Procedure:
• antiangiogenesis therapy

• biopsy

• diagnostic procedure

• gene expression analysis

• immunohistochemistry staining method

• laboratory biomarker analysis

• mutation analysis

• protein tyrosine kinase inhibitor therapy

• reverse transcriptase-polymerase chain reaction

Locations

Country	Name	City	State
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
Sidney Kimmel Comprehensive Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response Rate: The Total Number of Participants With Progression of Disease	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.	1 month	No