Overview

This trial is active, not recruiting.

Condition colorectal cancer
Treatments panitumumab, erlotinib hydrochloride, irinotecan hydrochloride
Phase phase 2
Target EGFR
Sponsor Northwestern University
Collaborator Genentech, Inc.
Start date July 2009
End date July 2017
Trial size 96 participants
Trial identifier NCT00940316, NU 07I4, OSI 4263s, STU00004101

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
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.
panitumumab Vectibix
Given intravenously 6mg/kg every 2 weeks
erlotinib hydrochloride Tarceva
Given orally 150mg daily
irinotecan hydrochloride Camptosar
Given intravenously 120mg/m2 for 6/6 genotype and 60mg/m2 for 6/7 genotype
(Experimental)
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.
panitumumab Vectibix
Given intravenously 6mg/kg every 2 weeks
erlotinib hydrochloride Tarceva
Given orally 150mg daily
irinotecan hydrochloride Camptosar
Given intravenously 120mg/m2 for 6/6 genotype and 60mg/m2 for 6/7 genotype
(Experimental)
Patients receive erlotinib hydrochloride and panitumumab as in arm B.
panitumumab Vectibix
Given intravenously 6mg/kg every 2 weeks
erlotinib hydrochloride Tarceva
Given orally 150mg daily

Primary Outcomes

Measure
Determine the tumor response rate
time frame: Every 8 weeks until disease progression

Secondary Outcomes

Measure
Determine the time to disease progression
time frame: 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
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

Eligibility Criteria

Male or female participants at least 18 years old.

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)

Additional Information

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
Principal investigator Al Benson, MD
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.
Trial information was received from ClinicalTrials.gov and was last updated in June 2016.
Information provided to ClinicalTrials.gov by Northwestern University.