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

Primary Purpose

Colorectal Cancer

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Irinotecan
Cetuximab
RAD001
Sponsored by
Hoosier Cancer Research Network
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Colorectal Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Northwestern University Feinberg School of Medicine
  • Medical & Surgical Specialists, LLC
  • Cancer Care Center of Southern Indiana
  • Oncology Hematology Associates of SW Indiana
  • IN Onc/Hem Associates
  • Indiana University Simon Cancer Center
  • St. Vincent Hospital & Health Centers
  • Community Regional Cancer Center
  • Arnett Cancer Care
  • Horizon Oncology Center
  • Monroe Medical Associates
  • Center for Cancer Care, Inc., P.C.
  • Northern Indiana Cancer Research Consortium
  • Siteman Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Arm A: Irinotecan + Cetuximab +/- RAD001

Arm B: Ironotecan + Cetuximab

Arm Description

Outcomes

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
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

Secondary Outcome Measures

To evaluate the pharmacokinetic (PK) profile for RAD001 after one cycle of therapy, on cycle 2 day 1
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

Full Information

First Posted
August 28, 2007
Last Updated
May 14, 2015
Sponsor
Hoosier Cancer Research Network
Collaborators
Novartis Pharmaceuticals, Pfizer
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1. Study Identification

Unique Protocol Identification Number
NCT00522665
Brief Title
Phase I/Randomized Phase II Study of Second Line Therapy With Irinotecan + Cetuximab +/- RAD001 for Colorectal Cancer
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2015
Overall Recruitment Status
Completed
Study Start Date
August 2007 (undefined)
Primary Completion Date
May 2011 (Actual)
Study Completion Date
February 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoosier Cancer Research Network
Collaborators
Novartis Pharmaceuticals, Pfizer

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
41 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm A: Irinotecan + Cetuximab +/- RAD001
Arm Type
Active Comparator
Arm Title
Arm B: Ironotecan + Cetuximab
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
Irinotecan
Intervention Description
Irinotecan 125 mg/m2 IV days 1 and 8
Intervention Type
Biological
Intervention Name(s)
Cetuximab
Intervention Description
Cetuximab 250mg/m2 IV days 1, 8 and 15
Intervention Type
Biological
Intervention Name(s)
RAD001
Intervention Description
Patients on Arm A will crossover and receive RAD001 at disease progression
Primary Outcome Measure Information:
Title
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
Title
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 Measure Information:
Title
To evaluate the pharmacokinetic (PK) profile for RAD001 after one cycle of therapy, on cycle 2 day 1
Time Frame
Phase I
Title
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gabriela Chiorean, M.D.
Organizational Affiliation
Hoosier Oncology Group, Inc.
Official's Role
Study Chair
Facility Information:
Facility Name
Northwestern University Feinberg School of Medicine
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Medical & Surgical Specialists, LLC
City
Galesburg
State/Province
Illinois
ZIP/Postal Code
61401
Country
United States
Facility Name
Cancer Care Center of Southern Indiana
City
Bloomington
State/Province
Indiana
ZIP/Postal Code
47403
Country
United States
Facility Name
Oncology Hematology Associates of SW Indiana
City
Evansville
State/Province
Indiana
ZIP/Postal Code
47714
Country
United States
Facility Name
IN Onc/Hem Associates
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Indiana University Simon Cancer Center
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
St. Vincent Hospital & Health Centers
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46206
Country
United States
Facility Name
Community Regional Cancer Center
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46256
Country
United States
Facility Name
Arnett Cancer Care
City
Lafayette
State/Province
Indiana
ZIP/Postal Code
47904
Country
United States
Facility Name
Horizon Oncology Center
City
Lafayette
State/Province
Indiana
ZIP/Postal Code
47905
Country
United States
Facility Name
Monroe Medical Associates
City
Munster
State/Province
Indiana
ZIP/Postal Code
46321
Country
United States
Facility Name
Center for Cancer Care, Inc., P.C.
City
New Albany
State/Province
Indiana
ZIP/Postal Code
47150
Country
United States
Facility Name
Northern Indiana Cancer Research Consortium
City
South Bend
State/Province
Indiana
ZIP/Postal Code
46601
Country
United States
Facility Name
Siteman Cancer Center
City
St. Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States

12. IPD Sharing Statement

Citations:
Citation
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)
Results Reference
result
Links:
URL
http://www.hoosiercancer.org
Description
Hoosier Cancer Research Network Homepage

Learn more about this trial

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

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