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

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

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.

Study Overview

• Status: Terminated
• Conditions: Colorectal Cancer
• Intervention / Treatment: Procedure: surgery; Radiation: radiation therapy; Drug: capecitabine; Drug: celecoxib

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.

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 2

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 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

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: celecoxib + capecitabine + radiation + surgery; 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.

Procedure: surgery; Radiation: radiation therapy; Drug: capecitabine; Drug: celecoxib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Proportion of successes	Up to 5 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Survival time	Up to 5 years
Survival	Up to 5 years
Time-to event analyses	Up to 5 years
Time to disease progression/recurrence	Up to 5 years
Time to recurrence	Up to 5 years
Time to first progression	Up to 5 years
Bowel function as measured by the Patient Bowel Function (Uniscale) Questionnaire, the FACT Diarrhea Subscale and the Mayo Bowel Function Questionnaire	Up to 5 years

Collaborators and Investigators

• Sponsor: Alliance for Clinical Trials in Oncology
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Frank Sinicrope, MD, Mayo Clinic

Study record dates

Study Major Dates

• Study Start: December 1, 2004
• Primary Completion (Actual): February 1, 2006
• Study Completion (Actual): November 1, 2010

Study Registration Dates

• First Submitted: April 7, 2004
• First Submitted That Met QC Criteria: April 7, 2004
• First Posted (Estimate): April 8, 2004

Study Record Updates

• Last Update Posted (Estimate): December 15, 2016
• Last Update Submitted That Met QC Criteria: December 14, 2016
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Keywords: adenocarcinoma of the rectum; stage II rectal cancer; stage III rectal cancer
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Adenocarcinoma; 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; Cyclooxygenase 2 Inhibitors; Capecitabine; Celecoxib
• Other Study ID Numbers: NCCTG-N0346; NCI-2012-02582 (Registry Identifier: CTRP (Clinical Trials Reporting System)); CDR0000360666 (Registry Identifier: PDQ (Physician Data Query))