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Trial record 1 of 1 for:    NCT00522665
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Phase I/Randomized Phase II Study of Second Line Therapy With Irinotecan + Cetuximab +/- RAD001 for Colorectal Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00522665
Recruitment Status : Completed
First Posted : August 30, 2007
Last Update Posted : May 15, 2015
Sponsor:
Collaborators:
Novartis Pharmaceuticals
Pfizer
Information provided by (Responsible Party):
Hoosier Cancer Research Network

Tracking Information
First Submitted Date  ICMJE August 28, 2007
First Posted Date  ICMJE August 30, 2007
Last Update Posted Date May 15, 2015
Study Start Date  ICMJE August 2007
Actual Primary Completion Date May 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 28, 2007)
  • 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 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 28, 2007)
  • 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 ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase I/Randomized Phase II Study of Second Line Therapy With Irinotecan + Cetuximab +/- RAD001 for Colorectal Cancer
Official Title  ICMJE 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
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.
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
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Colorectal Cancer
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • Active Comparator: Arm A: Irinotecan + Cetuximab +/- RAD001
    Interventions:
    • Drug: Irinotecan
    • Biological: Cetuximab
    • Biological: RAD001
  • Active Comparator: Arm B: Ironotecan + Cetuximab
    Interventions:
    • Drug: Irinotecan
    • Biological: Cetuximab
Publications * 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)

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 30, 2011)
41
Original Estimated Enrollment  ICMJE
 (submitted: August 28, 2007)
110
Actual Study Completion Date  ICMJE February 2015
Actual Primary Completion Date May 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00522665
Other Study ID Numbers  ICMJE GI05-102
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Hoosier Cancer Research Network
Study Sponsor  ICMJE Hoosier Cancer Research Network
Collaborators  ICMJE
  • Novartis Pharmaceuticals
  • Pfizer
Investigators  ICMJE
Study Chair: Gabriela Chiorean, M.D. Hoosier Oncology Group, Inc.
PRS Account Hoosier Cancer Research Network
Verification Date May 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP