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Phase I/Randomized Phase II Study of Second Line Therapy With Irinotecan + Cetuximab +/- RAD001 for Colorectal Cancer

This study has been completed.
Novartis Pharmaceuticals
Information provided by (Responsible Party):
Hoosier Cancer Research Network Identifier:
First received: August 28, 2007
Last updated: May 14, 2015
Last verified: May 2015
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.

Condition Intervention Phase
Colorectal Cancer
Drug: Irinotecan
Biological: Cetuximab
Biological: RAD001
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:

Further study details as provided by Hoosier Cancer Research Network:

Primary Outcome Measures:
  • To determine the MTD of RAD001 in combination with irinotecan and cetuximab as second line therapy in patients with metastatic colorectal cancer [ Time Frame: 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 [ Time Frame: Phase II ]

Secondary Outcome Measures:
  • To evaluate the pharmacokinetic (PK) profile for RAD001 after one cycle of therapy, on cycle 2 day 1 [ Time Frame: 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 [ Time Frame: Phase II ]

Enrollment: 41
Study Start Date: August 2007
Study Completion Date: February 2015
Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm A: Irinotecan + Cetuximab +/- RAD001 Drug: Irinotecan
Irinotecan 125 mg/m2 IV days 1 and 8
Biological: Cetuximab
Cetuximab 250mg/m2 IV days 1, 8 and 15
Biological: RAD001
Patients on Arm A will crossover and receive RAD001 at disease progression
Active Comparator: Arm B: Ironotecan + Cetuximab Drug: Irinotecan
Irinotecan 125 mg/m2 IV days 1 and 8
Biological: Cetuximab
Cetuximab 250mg/m2 IV days 1, 8 and 15

  Show Detailed Description


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

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  • No planned immunization with attenuated live viruses during the study period
  • Females must not be breastfeeding
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00522665

United States, Illinois
Northwestern University Feinberg School of Medicine
Chicago, Illinois, United States, 60611
Medical & Surgical Specialists, LLC
Galesburg, Illinois, United States, 61401
United States, Indiana
Cancer Care Center of Southern Indiana
Bloomington, Indiana, United States, 47403
Oncology Hematology Associates of SW Indiana
Evansville, Indiana, United States, 47714
IN Onc/Hem Associates
Indianapolis, Indiana, United States, 46202
Indiana University Simon Cancer Center
Indianapolis, Indiana, United States, 46202
St. Vincent Hospital & Health Centers
Indianapolis, Indiana, United States, 46206
Community Regional Cancer Center
Indianapolis, Indiana, United States, 46256
Arnett Cancer Care
Lafayette, Indiana, United States, 47904
Horizon Oncology Center
Lafayette, Indiana, United States, 47905
Monroe Medical Associates
Munster, Indiana, United States, 46321
Center for Cancer Care, Inc., P.C.
New Albany, Indiana, United States, 47150
Northern Indiana Cancer Research Consortium
South Bend, Indiana, United States, 46601
United States, Missouri
Siteman Cancer Center
St. Louis, Missouri, United States, 63110
Sponsors and Collaborators
Hoosier Cancer Research Network
Novartis Pharmaceuticals
Study Chair: Gabriela Chiorean, M.D. Hoosier Oncology Group, Inc.
  More Information

Additional Information:
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)

Responsible Party: Hoosier Cancer Research Network Identifier: NCT00522665     History of Changes
Other Study ID Numbers: GI05-102
Study First Received: August 28, 2007
Last Updated: May 14, 2015

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
Antineoplastic Agents, Phytogenic
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents processed this record on May 22, 2017