A Phase II Study of OSI-774 in Metastatic Colorectal Cancer
A Phase II Study of OSI-774 in Metastatic Colorectal Cancer
Biological therapies such as erlotinib may interfere with the growth of tumor cells and slow the growth of the tumor. Phase II trial to study the effectiveness of erlotinib in treating patients who have recurrent or metastatic colorectal cancer.
PRIMARY OBJECTIVES:
I. Determine the efficacy of erlotinib, in terms of response rate and duration of stable disease, in patients with recurrent or metastatic colorectal cancer.
II. Determine the toxicity of this drug in these patients. III. Determine the time to progression and response duration in patients treated with this drug.
IV. Determine the relationships between clinical, pharmacokinetic, and pharmacodynamic effects of this drug in these patients.
V. Correlate baseline and post-treatment levels of epidermal growth factor receptor, its downstream signaling components, markers of angiogenesis, and apoptosis in tumor and skin biopsies with clinical outcome in patients treated with this drug.
OUTLINE: This is a multicenter study.
Patients receive oral erlotinib once daily. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients with a complete response (CR) receive 2 additional courses after CR is confirmed.
Patients are followed every 8 weeks.
PROJECTED ACCRUAL: A total of 15-30 patients will be accrued for this study within 4-8 months.
Inclusion Criteria:
Histologically or cytologically confirmed adenocarcinoma of the colon or rectum that is not curable with conventional therapy
At least 1 unidimensionally measurable lesion
No known brain metastases
Performance status - ECOG 0-2
Performance status - Karnofsky 60-100%
More than 3 months
WBC at least 1,500/mm^3
Absolute granulocyte count at least 1,500/mm^3
Platelet count at least 100,000/mm^3
Bilirubin no greater than 1.25 times upper limit of normal (ULN)
AST or ALT no greater than 3 times ULN (5 times ULN if liver metastases present)
Creatinine no greater than 1.25 times ULN
Creatinine clearance at least 50 mL/min
No symptomatic congestive heart failure
No unstable angina pectoris
No cardiac arrhythmia
No gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation
No active peptic ulcer disease
No unresolved complete or subacute bowel obstruction
No severe enteropathy that would interfere with absorption of study drug
No abnormalities of the cornea:
No significant traumatic injury within the past 21 days
No ongoing or active infection
No psychiatric illness or social situation that would preclude study
No other concurrent uncontrolled illness that would preclude study
No other malignancy within the past 3 years except curatively treated nonmelanoma skin cancer or carcinoma in situ of the cervix
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No more than 1 prior chemotherapy regimen for metastatic disease with either fluorouracil (5-FU) and oxaliplatin or 5-FU and a topoisomerase inhibitor (e.g., irinotecan), OR 5-FU (or other single-agent fluoropyrimidine, such as capecitabine) followed by irinotecan for advanced disease
Prior adjuvant chemotherapy allowed
At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
See Disease Characteristics
At least 4 weeks since prior radiotherapy and recovered
At least 3 weeks since prior major surgery
No prior surgical procedures affecting absorption
No prior epidermal growth factor receptor-targeting therapy
No other concurrent investigational therapies
No other concurrent anticancer therapy
No concurrent combination anti-retroviral therapy for HIV-positive patients
No concurrent warfarin