Erlotinib in Treating Patients With Recurrent or 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.

Study Overview

• Status: Completed
• Conditions: Stage IV Colon Cancer; Stage IV Rectal Cancer; Recurrent Colon Cancer; Recurrent Rectal Cancer; Adenocarcinoma of the Rectum; Adenocarcinoma of the Colon
• Intervention / Treatment: Other: laboratory biomarker analysis; Other: pharmacological study; Drug: erlotinib hydrochloride

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.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Hospital Phase 2 Consortium

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment (erlotinib hydrochloride); Patients 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.	Other: laboratory biomarker analysis; Correlative studies; Other: pharmacological study; Correlative studies; Other Names: pharmacological studies; Drug: erlotinib hydrochloride; Given orally; Other Names: OSI-774; erlotinib; CP-358,774

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Objective response or disease stabilization	Up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Molecular changes with therapy	Will be examined using logistic regression or Fisher's exact tests as appropriate.	Up to 5 years

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Amit Oza, Princess Margaret Hospital Phase 2 Consortium

Study record dates

Study Major Dates

• Study Start: January 1, 2002
• Primary Completion (Actual): May 1, 2007
• Study Completion (Actual): May 1, 2007

Study Registration Dates

• First Submitted: March 8, 2002
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): April 15, 2015
• Last Update Submitted That Met QC Criteria: April 14, 2015
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Disease Attributes; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Recurrence; Adenocarcinoma; Rectal Neoplasms; Colonic Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Erlotinib Hydrochloride
• Other Study ID Numbers: NCI-2012-02459 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); N01CM17107 (U.S. NIH Grant/Contract); CDR0000069258; PHL-003 (Other Identifier: Princess Margaret Hospital Phase 2 Consortium); NCI-5378; 5378 (Other Identifier: CTEP)