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

NCT ID: NCT00940316

Last Updated: 2019-05-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 28 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-01-18
• Study Completion Date: 2015-01-31

Brief Summary

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.

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.

Conditions

Colorectal Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A: Erlotinib + Panitumumab + Irinotecan

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.

Group Type: EXPERIMENTAL

panitumumab

Intervention Type: BIOLOGICAL

Given intravenously 6mg/kg every 2 weeks

erlotinib hydrochloride

Intervention Type: DRUG

Given orally 150mg daily

irinotecan hydrochloride

Intervention Type: DRUG

Given intravenously 120mg/m2 for 6/6 genotype and 60mg/m2 for 6/7 genotype

Arm B: Erlotinib + Panitumumab

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.

Group Type: EXPERIMENTAL

panitumumab

Intervention Type: BIOLOGICAL

Given intravenously 6mg/kg every 2 weeks

erlotinib hydrochloride

Intervention Type: DRUG

Given orally 150mg daily

irinotecan hydrochloride

Intervention Type: DRUG

Given intravenously 120mg/m2 for 6/6 genotype and 60mg/m2 for 6/7 genotype

Arm C: Erlotinib + Panitumumab

Patients receive erlotinib hydrochloride and panitumumab as in arm B.

Group Type: EXPERIMENTAL

panitumumab

Intervention Type: BIOLOGICAL

Given intravenously 6mg/kg every 2 weeks

erlotinib hydrochloride

Intervention Type: DRUG

Given orally 150mg daily

Interventions

panitumumab

Given intravenously 6mg/kg every 2 weeks

Intervention Type: BIOLOGICAL

erlotinib hydrochloride

Given orally 150mg daily

Intervention Type: DRUG

irinotecan hydrochloride

Given intravenously 120mg/m2 for 6/6 genotype and 60mg/m2 for 6/7 genotype

Intervention Type: DRUG

Other Intervention Names

Vectibix; Tarceva; Camptosar; CPT-11

Eligibility Criteria

Inclusion 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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Genentech, Inc.

INDUSTRY

Sponsor Role: collaborator

OSI Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

Amgen

INDUSTRY

Sponsor Role: collaborator

Northwestern University

OTHER

Sponsor Role: lead

Responsible Party

Al Benson

Al Benson, MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Al Benson, MD

Role: PRINCIPAL_INVESTIGATOR

Northwestern University

Locations

Cancer Care & Hematology Specialists of Chicagoland

Arlington Heights, Illinois, United States

Northwestern University, Northwestern Medical Faculty Foundation

Chicago, Illinois, United States

Hematology/Oncology Associates

Chicago, Illinois, United States

Joliet Oncology-Hematology Associates, Ltd.

Joliet, Illinois, United States

Hope Cancer Center

Terre Haute, Indiana, United States

Cancer Center of Kansas

Wichita, Kansas, United States

Nebraska Methodist Hospital

Omaha, Nebraska, United States

Virtua Memorial (Regional Cancer Care Associates of Mount Holly)

Mount Holly, New Jersey, United States

Mercy Clinic Oncology and Hematology

Oklahoma City, Oklahoma, United States

The Jones Clinic

Germantown, Tennessee, United States

Countries

United States

Other Identifiers

STU00004101

Identifier Type: OTHER

Identifier Source: secondary_id

OSI 4263s

Identifier Type: OTHER

Identifier Source: secondary_id

NU 07I4

Identifier Type: -

Identifier Source: org_study_id