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Erlotinib in Treating Patients With Recurrent or Metastatic Colorectal Cancer

Phase 2
Completed
Conditions
Adenocarcinoma of the Rectum
Recurrent Rectal Cancer
Stage IV Rectal Cancer
Adenocarcinoma of the Colon
Stage IV Colon Cancer
Recurrent Colon Cancer
Interventions
Other: pharmacological study
Other: laboratory biomarker analysis
Registration Number
NCT00032110
Lead Sponsor
National Cancer Institute (NCI)
Brief Summary

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.

Detailed Description

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
30
Inclusion Criteria
  • Histologically or cytologically confirmed adenocarcinoma of the colon or rectum that is not curable with conventional therapy

    • Recurrent or metastatic disease
  • At least 1 unidimensionally measurable lesion

    • At least 20 mm by conventional techniques
    • At least 10 mm by spiral CT scan
    • Target lesion must not be in a previously irradiated field unless progression of this lesion has been documented
  • 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:

    • Dry eye syndrome or Sjogren's syndrome
    • Congenital abnormality (e.g., Fuch's dystrophy)
    • Abnormal slit-lamp examination using a vital dye (e.g., fluorescein or Bengal-Rose)
    • Abnormal corneal sensitivity test (Schirmer test or similar tear production test)
  • 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

    • Low molecular weight heparin allowed
Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Treatment (erlotinib hydrochloride)pharmacological studyPatients receive oral erlotinib once daily. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients with a CR receive 2 additional courses after CR is confirmed.
Treatment (erlotinib hydrochloride)erlotinib hydrochloridePatients receive oral erlotinib once daily. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients with a CR receive 2 additional courses after CR is confirmed.
Treatment (erlotinib hydrochloride)laboratory biomarker analysisPatients receive oral erlotinib once daily. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients with a CR receive 2 additional courses after CR is confirmed.
Primary Outcome Measures
NameTimeMethod
Objective response or disease stabilizationUp to 5 years
Secondary Outcome Measures
NameTimeMethod
Molecular changes with therapyUp to 5 years

Will be examined using logistic regression or Fisher's exact tests as appropriate.

Trial Locations

Locations (1)

Princess Margaret Hospital Phase 2 Consortium

🇨🇦

Toronto, Ontario, Canada

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