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

May 14, 2015 updated by: Hoosier Cancer Research Network

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
41

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
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
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
Phase II

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
To evaluate the pharmacokinetic (PK) profile for RAD001 after one cycle of therapy, on cycle 2 day 1
Time Frame: Phase I
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
Phase II

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Hoosier Cancer Research Network

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Pfizer
Novartis Pharmaceuticals

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Gabriela Chiorean, M.D., Hoosier Oncology Group, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General 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)

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 1, 2007

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 1, 2011

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 1, 2015

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 28, 2007

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 28, 2007

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 30, 2007

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 15, 2015

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 14, 2015

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2015

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • GI05-102

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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