Clinical trial NCT00940316: Dual Epidermal Growth Factor Receptor Inhibition With Erlotinib and Panitumumab With or Without Chemotherapy for Advanced Colorectal Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Colorectal Cancer
Keywords: recurrent colon cancer
stage IV colon cancer
recurrent rectal cancer
stage IV rectal cancer
Lead sponsor: Northwestern University
Sponsor class: OTHER
Collaborators: name: Genentech, Inc.
name: OSI Pharmaceuticals
name: Amgen
First posted: 2009-07-16
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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)

Primary outcomes:
measure: Tumor Response Rate Based on Complete Response (CR)+ Partial Response (PR) + Stable Disease (SD)
timeFrame: At baseline and every 8 weeks during treatment until progressive disease for maximum of 51 cycles where 1 cycle = 2 weeks.
Secondary outcomes:
measure: Time to Disease Progression
timeFrame: At baseline and every 8 weeks during treatment until disease progression and for a maximum of 51 cycles where 1 cycle = 2 weeks
measure: Time to Treatment Failure
timeFrame: From first day of study drug treatment until the date of stopping all study drugs for any reason for a maximum of 51 cycles where 1 cycle=2weeks
measure: Toxicity of the Combination of Study Drugs
timeFrame: Day 1 of every 2 week treatment cycle while on study treatment and 30 days after the last treatment for a maximum of 51 cycles.
measure: Effect on Downstream Targets of Epidermal Growth Factor Receptor (EGFR) in Skin Rash Associated With Pharmacologic EGFR Inhibition
timeFrame: At baseline and at a time-point reflecting maximum rash intensity during treatment, at a maximum of 51 cycles.
Other outcomes:
Locations:
city: Arlington Heights
country: United States
facility: Cancer Care & Hematology Specialists of Chicagoland
state: Illinois
city: Chicago
country: United States
facility: Northwestern University, Northwestern Medical Faculty Foundation
state: Illinois
city: Chicago
country: United States
facility: Hematology/Oncology Associates
state: Illinois
city: Joliet
country: United States
facility: Joliet Oncology-Hematology Associates, Ltd.
state: Illinois
city: Terre Haute
country: United States
facility: Hope Cancer Center
state: Indiana
city: Wichita
country: United States
facility: Cancer Center of Kansas
state: Kansas
city: Omaha
country: United States
facility: Nebraska Methodist Hospital
state: Nebraska
city: Mount Holly
country: United States
facility: Virtua Memorial (Regional Cancer Care Associates of Mount Holly)
state: New Jersey
city: Oklahoma City
country: United States
facility: Mercy Clinic Oncology and Hematology
state: Oklahoma
city: Germantown
country: United States
facility: The Jones Clinic
state: Tennessee
Study officials:
affiliation: Northwestern University
name: Al Benson, MD
role: PRINCIPAL_INVESTIGATOR
References: