Celecoxib, Capecitabine, and Irinotecan in Treating Patients With Recurrent or Metastatic Colorectal Cancer

Phase II Study of Celecoxib, Capecitabine, and Irinotecan in Patients With Metastatic Colorectal Cancer

RATIONALE: Celecoxib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as capecitabine and irinotecan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving celecoxib together with capecitabine and irinotecan may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving celecoxib together with capecitabine and irinotecan works in treating patients with recurrent or metastatic colorectal cancer.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: irinotecan hydrochloride; Drug: capecitabine; Drug: celecoxib

Detailed Description

OBJECTIVES:

Primary

• Determine the objective response rate in patients with locally recurrent or metastatic colorectal cancer treated with celecoxib, capecitabine, and irinotecan.

Secondary

• Determine the time to progression in patients treated with this regimen.
• Determine the toxicity of this regimen in these patients.
• Determine the overall survival of patients treated with this regimen.
• Determine the time to treatment failure in patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive oral celecoxib twice daily on days -7 to 21 during course 1 and on days 1-21 in all subsequent courses. Patients also receive oral capecitabine twice daily on days 1-14 and irinotecan IV over 30 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients achieving a complete or partial response after 4 courses may temporarily discontinue treatment for no more than 4 weeks.

After completion of study treatment, patients are followed every 6 months for survival.

PROJECTED ACCRUAL: A total of 21-44 patients will be accrued for this study within 7-18 months.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109-0944
      • University of Michigan Comprehensive Cancer Center
    • Detroit, Michigan, United States, 48201-1379
      • Barbara Ann Karmanos Cancer Institute
  • Ohio
    • Columbus, Ohio, United States, 43210-1240
      • Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University

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

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the colon or rectum

  • Locally recurrent or metastatic disease

• Measurable disease, defined as ≥ 1 measurable lesion ≥ 20 mm by conventional CT scan OR ≥ 10 mm by spiral CT scan

  • Bone metastases, ascites, and pleural effusion are not considered measurable disease
  • Measurable lesions must be located outside a previously irradiated field

PATIENT CHARACTERISTICS:

Performance status

• SWOG 0-2

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3

Hepatic

• Bilirubin normal
• No Gilbert's disease

Renal

• Creatinine clearance > 50 mL/min

Cardiovascular

• No clinically significant cardiac disease that is not well controlled by medication, including any of the following conditions:

  • Congestive heart failure
  • Symptomatic coronary artery disease
  • Cardiac arrhythmias
• No myocardial infarction within the past year

Gastrointestinal

• Must have a physically intact upper gastrointestinal tract
• Able to swallow tablets
• No history of peptic ulcer disease or gastroesophageal reflux
• No malabsorption syndrome

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No known HIV positivity
• No asthma, urticaria, or allergic-type reaction after prior treatment with aspirin or other nonsteroidal anti-inflammatory drugs
• No other malignancy except curatively treated cancer with no evidence of active disease
• No unresolved bacterial infection requiring antibiotics
• No other serious infection
• No known allergy to study drugs or sulfa drugs

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• No prior chemotherapy for colorectal cancer

  • Patients relapsing > 6 months after completion of prior adjuvant chemotherapy allowed
• No other concurrent anticancer chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• See Disease Characteristics
• At least 3 weeks since prior radiotherapy
• No concurrent anticancer radiotherapy

Surgery

• Recovered from prior surgery
• No concurrent anticancer surgery

Other

• Prior celecoxib for nonmalignant disorders allowed

• No other concurrent cyclooxygenase-2 inhibitors or nonsteroidal anti-inflammatory drugs, including any of the following:

  • Rofecoxib
  • Ibuprofen
  • Naproxen
  • Etodolac
  • Oxaprozin
  • Diflunisal
  • Nabumetone
  • Tolmetin

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Response rate by RECIST criteria at every other course

Secondary Outcome Measures

Outcome Measure
Toxicity
Time to progression
Time to treatment failure
Overall survival

Collaborators and Investigators

• Sponsor: Barbara Ann Karmanos Cancer Institute
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Philip A. Philip, MD, PhD, FRCP, Barbara Ann Karmanos Cancer Institute

Publications and helpful links

General Publications

• El-Rayes BF, Venkat R, Heilbrun LK: A dose attenuated schedule of irinotecan and capecitabine in combination with celecoxib in advanced colorectal cancer. [Abstract] American Society of Clinical Oncology 2006 Gastrointestinal Cancers Symposium, 26-28 January 2006, San Francisco, California. A-254, 2006.

Study record dates

Study Major Dates

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

Study Registration Dates

• First Submitted: November 22, 2005
• First Submitted That Met QC Criteria: November 22, 2005
• First Posted (Estimate): November 24, 2005

Study Record Updates

• Last Update Posted (Estimate): April 8, 2013
• Last Update Submitted That Met QC Criteria: April 5, 2013
• Last Verified: April 1, 2013

More Information

Terms related to this study

• Keywords: adenocarcinoma of the rectum; stage IV rectal cancer; stage IV colon cancer; adenocarcinoma of the colon; recurrent colon cancer; recurrent rectal cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Topoisomerase Inhibitors; Cyclooxygenase 2 Inhibitors; Topoisomerase I Inhibitors; Capecitabine; Celecoxib; Irinotecan
• Other Study ID Numbers: CDR0000445439; P30CA022453 (U.S. NIH Grant/Contract); WSU-C-2424