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

NCT00390364 | Terminated Phase 2 Results

• 3 other identifiers: J05107 CDR0000508071JHOC-J05107NOVARTIS-JHOC-J05107
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

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.

Conditions

Colorectal Cancer

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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

Interventions

everolimus DRUG

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 PROCEDURE

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21231-2410, United States

Location

MeSH Terms

Conditions

Colorectal Neoplasms; Colonic Neoplasms; Rectal Neoplasms

Interventions

Everolimus; Biopsy; Gene Expression Profiling; Immunohistochemistry; Reverse Transcriptase Polymerase Chain Reaction

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Genetic Techniques; Histocytochemistry; Histological Techniques; Immunologic Techniques; Polymerase Chain Reaction; Nucleic Acid Amplification Techniques

Limitations and Caveats

Out of 28 subjects pre-screened/screened, only one was enrolled and treated, and she progressed after 1 cycle. Study terminated by investigator because of low enrollment.

Results Point of Contact

• Title: Manuel Hidalgo, MD (no longer works at Hopkins)
• Organization: Sidney Kimmel Comprehensive Cancer Center at JHMI

tbrown55@jhmi.edu

410-502-5328

Study Officials

• Manuel Hidalgo, MD, PhD

  Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 18, 2006
• First Posted: October 19, 2006
• Study Start: October 1, 2006
• Primary Completion: October 1, 2007
• Study Completion: October 1, 2007
• Last Updated: October 8, 2014
• Results First Posted: October 8, 2014

Record last verified: 2014-10

Locations

US (1)