Neoadjuvant Celecoxib and Capecitabine Combined With Pelvic Irradiation in Treating Patients With Stage II or Stage III Adenocarcinoma (Cancer) of the Rectum

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00081224
First received: April 7, 2004
Last updated: November 5, 2010
Last verified: December 2005
  Purpose

RATIONALE: Celecoxib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Drugs used in chemotherapy, such as capecitabine, work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Celecoxib may also make tumor cells more sensitive to chemotherapy and radiation therapy. Giving celecoxib with capecitabine and radiation therapy before surgery may shrink the tumor so that it can be removed.

PURPOSE: This phase II trial is studying how well giving neoadjuvant celecoxib together with capecitabine and pelvic irradiation works in treating patients with stage II or stage III adenocarcinoma (cancer) of the rectum.


Condition Intervention Phase
Colorectal Cancer
Drug: capecitabine
Drug: celecoxib
Procedure: adjuvant therapy
Procedure: neoadjuvant therapy
Radiation: radiation therapy
Phase 2

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial Of Celecoxib (Celebrex) And Capecitabine (Xeloda) Combined With Pelvic Irradiation As Neoadjuvant Treatment Of Stage II or III Adenocarcinoma Of The Rectum

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Proportion of successes [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Survival time [ Designated as safety issue: No ]
  • Time-to event analyses [ Designated as safety issue: No ]
  • Time to disease progression/recurrence [ Designated as safety issue: No ]
  • Time to recurrence [ Designated as safety issue: No ]
  • Time to first progression [ Designated as safety issue: No ]
  • Survival [ Designated as safety issue: No ]
  • Bowel function as measured by the Patient Bowel Function (Uniscale) Questionnaire, the FACT Diarrhea Subscale and the Mayo Bowel Function Questionnaire [ Designated as safety issue: No ]

Study Start Date: December 2004
Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • Determine the pathological complete response rate in patients with stage II or III adenocarcinoma of the rectum treated with neoadjuvant celecoxib and capecitabine in combination with pelvic irradiation.

Secondary

  • Determine the safety and tolerability of this regimen in these patients.
  • Determine the rectal function of patients treated with this regimen.
  • Determine the time to recurrence or progression and survival time of patients treated with this regimen.
  • Correlate cellular and molecular markers in pretreatment tumor samples with response in patients treated with this regimen.

OUTLINE: This is a multicenter study.

  • Neoadjuvant chemoradiotherapy: Patients receive oral celecoxib twice daily on days 1-7 and oral capecitabine twice daily on days 1-5. Patients undergo pelvic radiotherapy once daily on days 1-5. Courses repeat weekly for 5.5 weeks.
  • Surgery: Patients undergo surgery 4-6 weeks after completion of neoadjuvant chemoradiotherapy.
  • Adjuvant chemotherapy: Patients with a curative resection receive oral capecitabine twice daily on days 1-14. Treatment repeats every 21 days for up to 4 courses.

Treatment continues in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 1 year and then every 6 months for 4 years.

PROJECTED ACCRUAL: A total of 23-55 patients will be accrued for this study within 10-28 months.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed rectal adenocarcinoma

    • Clinical stage T3, N0, M0 OR any T, N1-3, M0 disease
  • Treatment with neoadjuvant chemotherapy and pelvic radiotherapy is indicated

    • All disease must be encompassable within standard pelvic radiotherapy fields
  • Distal border of the tumor must be at or below* the peritoneal reflection, defined as within 12 cm of the anal verge by endoscopy NOTE: *If a portion of the tumor is below the peritoneal reflection at the time of surgery, patients are eligible regardless of the distance of the tumor determined at endoscopy
  • Tumor must be determined to be clinically resectable

    • Tumor may not be clinically fixed
    • Negative margins by routine examination of an unanesthetized patient
  • Transmural penetration of tumor through the muscularis propria by CT scan, endorectal ultrasound, or MRI
  • No distant metastatic disease

    • No evidence of tumor outside the pelvis, including any of the following:

      • Metastatic inguinal lymphadenopathy
      • Peritoneal seeding
      • Liver metastases

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Performance status

  • ECOG 0-1

Life expectancy

  • At least 6 months

Hematopoietic

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

Hepatic

  • Bilirubin ≤ upper limit of normal (ULN)
  • AST ≤ 3 times ULN
  • Alkaline phosphatase ≤ 4 times ULN if AST < ULN

Renal

  • Creatinine clearance ≥ 30 mL/min
  • No renal impairment

Cardiovascular

  • No congestive heart failure
  • No symptomatic coronary artery disease
  • No uncontrolled cardiac arrhythmias
  • No myocardial infarction
  • No history of transient ischemic attacks or stroke
  • No other clinically significant cardiac disease

Gastrointestinal

  • No bleeding peptic ulcer disease within the past 12 months
  • No lack of physical integrity of the upper gastrointestinal tract
  • No malabsorption syndrome
  • No active inflammatory bowel disease
  • Must be able to swallow study drugs

Other

  • No dihydropyrimidine dehydrogenase deficiency
  • No history of uncontrolled seizures
  • No CNS disorders
  • No clinically significant psychiatric illness that would preclude study compliance or giving informed consent
  • No other malignancy within the past 5 years except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
  • No known sensitivity to NSAIDs, sulfonamides, or aspirin
  • No other serious medical illness that would preclude study treatment
  • No other conditions that would preclude study participation
  • Must be able to tolerate major surgery that may include abdominal-perineal resection
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 30 days after study treatment

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • Not specified

Chemotherapy

  • See Disease Characteristics
  • No prior systemic anticancer chemotherapy

Endocrine therapy

  • Not specified

Radiotherapy

  • See Disease Characteristics
  • No prior radiotherapy to the pelvis

Surgery

  • See Disease Characteristics
  • More than 3 weeks since prior major surgery and recovered

Other

  • At least 7 days since prior nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin
  • No other concurrent investigational drugs
  • No other concurrent anticancer treatment
  • No concurrent NSAIDs
  • No concurrent primary prophylactic therapy for hand-foot syndrome
  • No concurrent loperamide prophylaxis for diarrhea
  • No concurrent sorivudine or brivudine
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00081224

Sponsors and Collaborators
North Central Cancer Treatment Group
Investigators
Study Chair: Frank Sinicrope, MD Mayo Clinic
Investigator: James A. Martenson, MD Mayo Clinic
Investigator: Richard L. Deming, MD Mercy Therapeutic Radiology Associates, PC at Mercy Medical Center - Des Moines
Investigator: Heidi Nelson, MD Mayo Clinic
Investigator: James D. Bearden, MD CCOP - Upstate Carolina
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00081224     History of Changes
Other Study ID Numbers: CDR0000360666, NCCTG-N0346
Study First Received: April 7, 2004
Last Updated: November 5, 2010
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
adenocarcinoma of the rectum
stage II rectal cancer
stage III rectal cancer

Additional relevant MeSH terms:
Adenocarcinoma
Colorectal Neoplasms
Rectal Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Celecoxib
Capecitabine
Fluorouracil
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 20, 2014