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
18 Years
N/A
Both
Colorectal Cancer
Trial Information
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
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.
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)
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Determine the tumor response rate
Outcome Description:
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.
Outcome Time Frame:
Every 8 weeks until disease progression
Safety Issue:
No
Principal Investigator
Al Benson, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Northwestern University
Authority:
United States: Food and Drug Administration
Study ID:
NU 07I4
NCT ID:
NCT00940316
Start Date:
July 2009
Completion Date:
July 2016
Related Keywords:
- Colorectal Cancer
- recurrent colon cancer
- stage IV colon cancer
- recurrent rectal cancer
- stage IV rectal cancer
- Colorectal Neoplasms
Name | Location |
|---|---|
| Joliet Oncology-Hematology Associates, Ltd. | Flossmoor, Illinois 60422 |
| Northwestern University, Northwestern Medical Faculty Foundation | Chicago, Illinois 60611-3013 |
| Cancer Care & Hematology Specialists of Chicagoland | Niles, Illinois 60714 |
| Hematology/Oncology Associates | Chicago, Illinois 60611 |
