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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Genentech, Inc.
OSI Pharmaceuticals
Amgen
Information provided by (Responsible Party):
Al Benson, Northwestern University
ClinicalTrials.gov Identifier:
NCT00940316
First received: July 15, 2009
Last updated: April 13, 2015
Last verified: April 2015
  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:


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 2017
Estimated Primary Completion Date: July 2016 (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
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: NCT00940316

Locations
United States, Illinois
Cancer Care & Hematology Specialists of Chicagoland
Arlington Heights, Illinois, United States, 60005
Hematology/Oncology Associates
Chicago, Illinois, United States, 60611
Northwestern University, Northwestern Medical Faculty Foundation
Chicago, Illinois, United States, 60611-3013
Joliet Oncology-Hematology Associates, Ltd.
Joliet, Illinois, United States, 60435
United States, Indiana
Hope Cancer Center
Terre Haute, Indiana, United States, 47802
United States, Kansas
Cancer Center of Kansas
Wichita, Kansas, United States, 67214
United States, Nebraska
Nebraska Methodist Hospital
Omaha, Nebraska, United States, 68114
United States, New Jersey
Virtua Memorial (Regional Cancer Care Associates of Mount Holly)
Mount Holly, New Jersey, United States, 08060
United States, Oklahoma
Mercy Clinic Oncology and Hematology
Oklahoma City, Oklahoma, United States, 73120-9309
United States, Tennessee
The Jones Clinic
Germantown, Tennessee, United States, 38138
Sponsors and Collaborators
Northwestern University
Genentech, Inc.
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: April 13, 2015
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
Colonic Diseases
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Intestinal Diseases
Intestinal Neoplasms
Neoplasms
Neoplasms by Site
Rectal Diseases
Camptothecin
Erlotinib
Irinotecan
Mitogens
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Enzyme Inhibitors
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors
Radiation-Sensitizing Agents
Therapeutic Uses
Topoisomerase I Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on July 01, 2015