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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Novartis Pharmaceuticals
Pfizer
Information provided by (Responsible Party):
Hoosier Cancer Research Network
ClinicalTrials.gov Identifier:
NCT00522665
First received: August 28, 2007
Last updated: March 14, 2014
Last verified: March 2014
  Purpose

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
Endpoint Classification: Safety/Efficacy Study
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 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]

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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Enrollment: 41
Study Start Date: August 2007
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (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

  Hide Detailed Description

Detailed Description:

OUTLINE: This is a multi-center study.

PHASE I:

  • UGT1A1 *28 7/7 genotype IS NOT present
  • Cetuximab 250 mg/m2 IV days 1, 8, and 15
  • Irinotecan 125 mg/m2 IV days 1 and 8
  • RAD001 PO QD (dose determined at the time of registration; subjects will remain at this dose level until treatment discontinuation)

PHASE II:

  • Randomization based on UGT1A1 *28 7/7 Genotype or Prior Irinotecan Exposure

ARM A:

  • Cetuximab 250 mg/m2 IV days 1, 8, and 15
  • Irinotecan 125 mg/m2 IV days 1 and 8

AT TIME OF PROGRESSIVE DISEASE, ARM A TREATMENT WILL CROSSOVER:

  • Cetuximab 250 mg/m2 IV days 1, 8, and 15
  • Irinotecan 125 mg/m2 IV days 1 and 8
  • RAD001 PO QD (maximum tolerated dose)

ARM B:

  • Cetuximab 250 mg/m2 IV days 1, 8, and 15
  • Irinotecan 125 mg/m2 IV days 1 and 8
  • RAD001 PO QD (maximum tolerated dose)

AT TIME OF PROGRESSIVE DISEASE, ARM B TREATMENT WILL BE DISCONTINUED

ECOG performance status 0-2

Life Expectancy: Not specified

Hematopoietic:

  • Absolute neutrophil count (ANC) ≥ 1,500 mm3
  • Platelets ≥ 100,000 mm3
  • Hemoglobin (Hgb) ≥ 9 g/dL
  • White blood cell count (WBC) ≥ 2,000 mm3
  • INR < 1.5 x upper limit of normal (ULN) if not on anticoagulation (if on anticoagulation must have an in-range INR (usually between 2 and 3) on a stable dose of warfarin)
  • PTT < 1.5 x ULN

Hepatic:

  • Bilirubin ≤ 1.5 x ULN
  • Aspartate aminotransferase (AST, SGOT) ≤ 2.5 x ULN
  • Alanine aminotransferase (ALT, SGPT) ≤ 2.5 x ULN
  • Albumin ≥ 3.0 g/dL

Renal:

  • Calculated creatinine clearance of ≥ 60 cc/min using the Cockcroft-Gault formula

Cardiovascular:

  • No uncontrolled cardiac arrhythmia requiring medication, transient ischemic attack (TIA), or cerebrovascular accident (CVA) within 6 months prior to being registered for protocol therapy
  • No uncontrolled congestive heart failure, myocardial infarction, or unstable angina within 6 months prior to being registered for protocol therapy

Pulmonary:

  • No severely impaired lung function as demonstrated by pulse O2 saturation ≤ 90% at rest on room air, or pulmonary function test FEV1 ≤ 2L
  • No history of prior chronic lung infection such as tuberculosis, atypical tuberculosis, or histoplasmosis as evidenced by a chest CT or x-ray within 21 days prior to being registered for protocol therapy
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 ClinicalTrials.gov identifier: NCT00522665

Locations
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
Horizon Oncology Center
Lafayette, Indiana, United States, 47905
Arnett Cancer Care
Lafayette, Indiana, United States, 47904
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
Pfizer
Investigators
Study Chair: Gabriela Chiorean, M.D. Hoosier Oncology Group, Inc.
  More Information

Additional Information:
No publications provided

Responsible Party: Hoosier Cancer Research Network
ClinicalTrials.gov Identifier: NCT00522665     History of Changes
Other Study ID Numbers: GI05-102
Study First Received: August 28, 2007
Last Updated: March 14, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Colorectal Neoplasms
Colonic Diseases
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Intestinal Diseases
Intestinal Neoplasms
Neoplasms
Neoplasms by Site
Rectal Diseases
Cetuximab
Everolimus
Irinotecan
Sirolimus
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Therapeutic Uses
Topoisomerase I Inhibitors

ClinicalTrials.gov processed this record on November 20, 2014