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Dual Epidermal Growth Factor Receptor Inhibition With Erlotinib and Panitumumab With or Without Chemotherapy for Advanced Colorectal Cancer

This study is currently recruiting participants.
Verified October 2012 by Northwestern University
Sponsor:
Collaborators:
Genentech
OSI Pharmaceuticals
Amgen
Information provided by (Responsible Party):
Al Benson, Northwestern University
ClinicalTrials.gov Identifier:
NCT00940316
First received: July 15, 2009
Last updated: October 30, 2012
Last verified: October 2012
History of Changes
  Purpose

RATIONALE: Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as panitumumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Panitumumab may also stop the growth of colorectal cancer by blocking blood flow to the tumor. Drugs used in chemotherapy, such as irinotecan hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether erlotinib hydrochloride given together with panitumumab is more effective with or without irinotecan in treating patients with metastatic colorectal cancer.

PURPOSE: This randomized phase II trial is studying giving erlotinib hydrochloride together with panitumumab to see how well it works with or without irinotecan hydrochloride as second-line therapy in treating patients with metastatic colorectal cancer.


Condition Intervention Phase
Colorectal Cancer
 Biological: panitumumab
Drug: erlotinib hydrochloride
Drug: irinotecan hydrochloride
 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Phase II Study of Dual Epidermal Growth Factor Receptor Inhibition With Erlotinib and Panitumumab With or Without Irinotecan as Second Line Therapy in Patients With Metastatic Colorectal Cancer

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Northwestern University:

Primary Outcome Measures:
  • Determine the tumor response rate [ Time Frame: Every 8 weeks until disease progression ] [ Designated as safety issue: No ]
    Tumor response rate will be measured by CT scan of the chest and CT scan or MRI scan of abdomen and pelvis every 8 weeks until disease progression.


Secondary Outcome Measures:
  • Determine the time to disease progression [ Time Frame: Every 8 weeks until disease progression ] [ Designated as safety issue: No ]
    Time to disease progression will be measured by CT scan of the chest and CT scan or MRI scan of abdomen and pelvis every 8 weeks until disease progression.

  • Determine the time to treatment failure [ Time Frame: From first day of study drug treatment until the date of stopping all study drugs for any reason ] [ Designated as safety issue: No ]
    Time to treatment failure will be measured as the time elapsed from the day of first study drug administration to the date a subject stops all study drugs for any reason.

  • Collect data on the toxicity of the combination of study drugs [ Time Frame: Day 1 of every treatment cycle while on study treatment and every 6 weeks while in long term follow-up ] [ Designated as safety issue: Yes ]
    Data on the toxicity of the combination of study drugs will be assessed by laboratory blood draws done on day 1 of every treatment cycle while on study treatment and every 6 weeks while in long term follow-up.


Estimated Enrollment: 96
Study Start Date: July 2009
Estimated Study Completion Date: July 2016
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A
Patients receive oral erlotinib hydrochloride once daily on days 1-14, panitumumab IV over 30-90 minutes on day 1, and irinotecan hydrochloride IV over 90 minutes on day 1. Treatment repeats every 2 weeks in the absence of disease progression or unacceptable toxicity.
 Biological: panitumumab
Given intravenously 6mg/kg every 2 weeks
Other Name: Vectibix
Drug: erlotinib hydrochloride
Given orally 150mg daily
Other Name: Tarceva
Drug: irinotecan hydrochloride
Given intravenously 120mg/m2 for 6/6 genotype and 60mg/m2 for 6/7 genotype
Other Names:
  • Camptosar
  • CPT-11
Experimental: Arm B
Patients receive oral erlotinib hydrochloride once daily on days 1-14 and panitumumab IV over 30-90 minutes on day 1. Treatment repeats every 2 weeks in the absence of disease progression or unacceptable toxicity. Upon disease progression, patients receive irinotecan hydrochloride as in arm A.
 Biological: panitumumab
Given intravenously 6mg/kg every 2 weeks
Other Name: Vectibix
Drug: erlotinib hydrochloride
Given orally 150mg daily
Other Name: Tarceva
Drug: irinotecan hydrochloride
Given intravenously 120mg/m2 for 6/6 genotype and 60mg/m2 for 6/7 genotype
Other Names:
  • Camptosar
  • CPT-11
Experimental: Arm C
Patients receive erlotinib hydrochloride and panitumumab as in arm B.
 Biological: panitumumab
Given intravenously 6mg/kg every 2 weeks
Other Name: Vectibix
Drug: erlotinib hydrochloride
Given orally 150mg daily
Other Name: Tarceva

Detailed Description:

OBJECTIVES:

Primary

  • Determine the response rate in patients with metastatic colorectal cancer treated with erlotinib hydrochloride and panitumumab with versus without irinotecan hydrochloride as second-line therapy .

Secondary

  • Determine time to disease progression and time to treatment failure in patients treated with these regimens.
  • Determine the safety of these regimens in these patients.
  • Determine the effect of these regimens on downstream targets of EGFR in skin rash associated with pharmacologic EGFR inhibition (exploratory).
  • Determine the association between KRAS mutations and response to EGFR inhibition (exploratory).

OUTLINE: This is a multicenter study. Patients are stratified according to wild-type Kras tumors ( 6/6 UGT1A1 vs 6/7 UGT1A1), and are randomized to 1 of 2 treatment arms. Patients with wild-type Kras tumor 7/7 UGT1A1 receive treatment in arm III.

  • Arm I: Patients receive oral erlotinib hydrochloride once daily on days 1-14, panitumumab IV over 30-90 minutes on day 1, and irinotecan hydrochloride IV over 90 minutes on day 1. Treatment repeats every 2 weeks in the absence of disease progression or unacceptable toxicity.
  • Arm II: Patients receive oral erlotinib hydrochloride once daily on days 1-14 and panitumumab IV over 30-90 minutes on day 1. Treatment repeats every 2 weeks in the absence of disease progression or unacceptable toxicity. Upon disease progression, patients receive irinotecan hydrochloride as in arm I.
  • Arm III: Patients receive erlotinib hydrochloride and panitumumab as in arm II. Skin biopsies and blood samples may be collected for further analysis.

After completion of study therapy, patients are followed every 6 weeks.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Histologically confirmed colorectal cancer

    • Metastatic disease

      • Biopsy of either the primary cancer or metastatic site required
    • Tumor expressing wild-type Kras mutations
  • Progressive disease within 3 months after treatment with first-line fluorouracil (5-FU) and oxaliplatin-based chemotherapy OR evidence of metastatic disease within 6 months of completing adjuvant therapy with 5-FU and oxaliplatin
  • Measurable disease defined as ≥ 1 lesion that can be accurately measured in ≥ 1 dimension (longest diameter to be recorded) as ≥ 20 mm with conventional techniques OR as ≥ 10 mm with spiral CT scan

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-2
  • Life expectancy > 6 months
  • ANC > 1,500/mm^3
  • Platelet count > 100,000/mm^3
  • Hemoglobin ≥ 9 g/dL
  • Creatinine < 1.5 times upper limit of normal (ULN)
  • Bilirubin < 1.5 times ULN (or < 2 mg/dL)
  • AST and/or ALT < 3 times ULN (< 5 times ULN with liver metastases)
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No concurrent malignancy requiring therapy except minor surgery for non-melanoma skin cancer removal

  • No interstitial lung disease with symptoms (e.g., dyspnea or cough) including any of the following significant conditions:

    • Parenchymal lung disease
    • Metastatic disease
    • Pulmonary infections

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • No prior EGFR inhibitors, irinotecan hydrochloride, or other second-line chemotherapy regimens
  • More than 4 weeks since prior radiotherapy
  • No other concurrent investigational agents
  • No other concurrent anticancer treatment modalities (e.g., radiotherapy)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00940316

Contacts
Contact: Al Benson, MD 312-695-6180 ABenson@nmff.org
Contact: Study Coordinator 312-695-1301 cancertrials@northwestern.edu

Locations
United States, Illinois
Cancer Care & Hematology Specialists of Chicagoland Recruiting
Arlington Heights, Illinois, United States, 60005
Contact: Richard Siegel, MD     847-259-4517     richard.siegel@usoncology.com    
Principal Investigator: Richard Siegel, MD            
Northwestern University, Northwestern Medical Faculty Foundation Recruiting
Chicago, Illinois, United States, 60611-3013
Contact: Study Coordinator     312-695-1301     cancertrials@northwestern.edu    
Principal Investigator: Al Benson, MD            
Sub-Investigator: Mary Mulcahy, MD            
Sub-Investigator: John Cotliar, MD            
Hematology/Oncology Associates Recruiting
Chicago, Illinois, United States, 60611
Contact: Ann Mellott, MD     312-664-5400     alm452@md.northwestern.edu    
Principal Investigator: Ann Mellott, MD            
Joliet Oncology-Hematology Associates, Ltd. Recruiting
Joliet, Illinois, United States, 60435
Contact: Kulumani Sivarajan, MD     815-725-1355     kmsiv@jolietoncology.com    
Principal Investigator: Kulumani Sivarajan, MD            
Sponsors and Collaborators
Northwestern University
Genentech
OSI Pharmaceuticals
Amgen
Investigators
Principal Investigator: Al Benson, MD Northwestern University
  More Information

No publications provided

Responsible Party: Al Benson, Al Benson, MD, Northwestern University
ClinicalTrials.gov Identifier: NCT00940316     History of Changes
Other Study ID Numbers: NU 07I4, STU00004101, OSI 4263s
Study First Received: July 15, 2009
Last Updated: October 30, 2012
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Northwestern University:
recurrent colon cancer
stage IV colon cancer
recurrent rectal cancer
stage IV rectal cancer

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Mitogens
Irinotecan
Camptothecin
Erlotinib
 Antibodies, Monoclonal
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Immunologic Factors
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on May 23, 2013