Phase I/Randomized Phase II Study of Second Line Therapy With Irinotecan + Cetuximab +/- RAD001 for Colorectal Cancer
Phase I / Randomized Phase II Study of Second Line Therapy With Irinotecan and Cetuximab With or Without RAD001, an Oral mTOR Inhibitor for Patients With Metastatic Colorectal Cancer: Hoosier Oncology Group GI05-102
1 other identifier
interventional
41
1 country
14
Brief Summary
The addition of RAD001, an mTOR inhibitor, to irinotecan and anti-EGFR antibody cetuximab may increase efficacy for patients with metastatic colorectal cancer who progressed on prior chemotherapy. This approach is biologically directed to overall target the cancer cell at multiple levels, and potentially preventing chemotherapy and EGFR-therapy resistance.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1 colorectal-cancer
Started Aug 2007
Longer than P75 for phase_1 colorectal-cancer
14 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
August 1, 2007
CompletedFirst Submitted
Initial submission to the registry
August 28, 2007
CompletedFirst Posted
Study publicly available on registry
August 30, 2007
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 1, 2011
CompletedStudy Completion
Last participant's last visit for all outcomes
February 1, 2015
CompletedMay 15, 2015
May 1, 2015
3.8 years
August 28, 2007
May 14, 2015
Conditions
Outcome Measures
Primary Outcomes (2)
To determine the MTD of RAD001 in combination with irinotecan and cetuximab as second line therapy in patients with metastatic colorectal cancer
Phase I
To evaluate the objective response (CR or PR) rates of patients treated with irinotecan and cetuximab with or without RAD001 in patients with metastatic colorectal cancer
Phase II
Secondary Outcomes (2)
To evaluate the pharmacokinetic (PK) profile for RAD001 after one cycle of therapy, on cycle 2 day 1
Phase I
To evaluate the time to progression, duration of objective response (CR or PR) and overall survival of patients treated with irinotecan and cetuximab with or without RAD001
Phase II
Study Arms (2)
Arm A: Irinotecan + Cetuximab +/- RAD001
ACTIVE COMPARATORArm B: Ironotecan + Cetuximab
ACTIVE COMPARATORInterventions
Irinotecan 125 mg/m2 IV days 1 and 8
Cetuximab 250mg/m2 IV days 1, 8 and 15
Patients on Arm A will crossover and receive RAD001 at disease progression
Eligibility Criteria
You may qualify if:
- Histological or cytological proof of colon or rectal adenocarcinoma
- Measurable site of disease according to RECIST that has not been previously irradiated
- Must have metastatic colorectal cancer which progressed after first line chemotherapy +/- bevacizumab
- Blood sample collected within 21 days prior to being registered for protocol therapy for UTG1A1 genotype analysis. (Patients with the UGT1A1 \*28 7/7 genotype (homozygosity for the TA7 allele) will be excluded from the Phase I stage of the study. During the Phase II stage of the study, subjects will be allowed to participate but must begin treatment at dose level -1 of irinotecan.)
- A history of other malignancies (non-colorectal) is allowed, provided it has been curatively treated and demonstrates no evidence for recurrence of that cancer
- Prior radiation therapy allowed to \< 25% of the bone marrow
- Age ≥ 18 years at the time of consent
- Written informed consent and HIPAA authorization for release of personal health information
- Females of childbearing potential and males must be willing to use an effective method of contraception
- Females of childbearing potential must have a negative pregnancy test within 7 days of being registered for protocol therapy
You may not qualify if:
- No more than one prior chemotherapy regimen for metastatic colorectal cancer, at least 28 days prior to being registered for protocol therapy
- No prior treatment with cetuximab
- No prior treatment with an mTOR inhibitor
- No known hypersensitivity to cetuximab, RAD001 (everolimus), other rapamycins (sirolimus, temsirolimus) or to its excipients
- No treatment with any investigational agent within 28 days prior to being registered for protocol therapy
- No symptomatic brain metastasis
- No uncontrolled diabetes as defined by a fasting serum glucose \>1.5 x ULN
- No chronic treatment with systemic steroids or another immuno-suppressive agent
- No serious non-healing wound, ulcer, bone fracture, major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to being registered for protocol therapy
- No liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis
- No active bleeding or a pathological condition that is associated with a high risk of bleeding
- No uncontrolled systemic disease including active infections or uncontrolled hypertension
- No known history of HIV seropositivity
- No impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of RAD001 (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)
- No nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the treatment with protocol therapy
- +2 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Hoosier Cancer Research Networklead
- Novartis Pharmaceuticalscollaborator
- Pfizercollaborator
Study Sites (14)
Northwestern University Feinberg School of Medicine
Chicago, Illinois, 60611, United States
Medical & Surgical Specialists, LLC
Galesburg, Illinois, 61401, United States
Cancer Care Center of Southern Indiana
Bloomington, Indiana, 47403, United States
Oncology Hematology Associates of SW Indiana
Evansville, Indiana, 47714, United States
IN Onc/Hem Associates
Indianapolis, Indiana, 46202, United States
Indiana University Simon Cancer Center
Indianapolis, Indiana, 46202, United States
St. Vincent Hospital & Health Centers
Indianapolis, Indiana, 46206, United States
Community Regional Cancer Center
Indianapolis, Indiana, 46256, United States
Arnett Cancer Care
Lafayette, Indiana, 47904, United States
Horizon Oncology Center
Lafayette, Indiana, 47905, United States
Monroe Medical Associates
Munster, Indiana, 46321, United States
Center for Cancer Care, Inc., P.C.
New Albany, Indiana, 47150, United States
Northern Indiana Cancer Research Consortium
South Bend, Indiana, 46601, United States
Siteman Cancer Center
St Louis, Missouri, 63110, United States
Related Publications (1)
Chiorean EG, Picus J, Breen T, Ansari RH, Harb WA, Burns M, Spittler AJ, Loehrer PJ. Phase I/II study of everolimus (E) with irinotecan (Iri) and cetuximab (C) in 2nd line metastatic colorectal cancer (mCRC): Hoosier Cancer Research Network GI05-102. J Clin Oncol 33:5s, 2015 (suppl; abstr 3618)
RESULT
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
Gabriela Chiorean, M.D.
Hoosier Oncology Group, Inc.
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- CROSSOVER
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 28, 2007
First Posted
August 30, 2007
Study Start
August 1, 2007
Primary Completion
May 1, 2011
Study Completion
February 1, 2015
Last Updated
May 15, 2015
Record last verified: 2015-05