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”

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 Type: Interventional

Study Design: Treatment, Open Label

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.

Intervention(s) in this Clinical Trial

• Drug: capecitabine
• Drug: celecoxib
• Procedure: adjuvant therapy
• Procedure: neoadjuvant therapy
• Procedure: radiation therapy

Primary Measures

• Proportion of successes
  • Safety Issue?: No

Secondary Measures

• Survival time
  • Safety Issue?: No
• Time-to event analyses
  • Safety Issue?: No
• Time to disease progression/recurrence
  • Safety Issue?: No
• Time to recurrence
  • Safety Issue?: No
• Time to first progression
  • Safety Issue?: No
• Survival
  • Safety Issue?: No
• Bowel function as measured by the Patient Bowel Function (Uniscale) Questionnaire, the FACT Diarrhea Subscale and the Mayo Bowel Function Questionnaire
  • Safety Issue?: No

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: North Central Cancer Treatment Group

Overall Clinical Trial Officials and Contacts

Frank Sinicrope, MD Study Chair Mayo Clinic  

Information obtained from ClinicalTrials.gov on August 28, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00081224

Study ID Number: CDR0000360666

ClinicalTrials.gov Identifier: NCT00081224

Health Authority: United States: Federal Government

Clinical trial summary from the National Cancer Institute's PDQ® database