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

Primary Purpose

Colorectal Cancer

Status
Terminated
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
capecitabine
celecoxib
radiation therapy
surgery
Sponsored by
Alliance for Clinical Trials in Oncology
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Colorectal Cancer focused on measuring adenocarcinoma of the rectum, stage II rectal cancer, stage III rectal cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    celecoxib + capecitabine + radiation + surgery

    Arm Description

    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.

    Outcomes

    Primary Outcome Measures

    Proportion of successes

    Secondary Outcome Measures

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

    Full Information

    First Posted
    April 7, 2004
    Last Updated
    December 14, 2016
    Sponsor
    Alliance for Clinical Trials in Oncology
    Collaborators
    National Cancer Institute (NCI)
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    1. Study Identification

    Unique Protocol Identification Number
    NCT00081224
    Brief Title
    Neoadjuvant Celecoxib and Capecitabine Combined With Pelvic Irradiation in Treating Patients With Stage II or Stage III Adenocarcinoma (Cancer) of the Rectum
    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
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    December 2016
    Overall Recruitment Status
    Terminated
    Study Start Date
    December 2004 (undefined)
    Primary Completion Date
    February 2006 (Actual)
    Study Completion Date
    November 2010 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Alliance for Clinical Trials in Oncology
    Collaborators
    National Cancer Institute (NCI)

    4. Oversight

    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    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.
    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Colorectal Cancer
    Keywords
    adenocarcinoma of the rectum, stage II rectal cancer, stage III rectal cancer

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    3 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    celecoxib + capecitabine + radiation + surgery
    Arm Type
    Experimental
    Arm Description
    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.
    Intervention Type
    Drug
    Intervention Name(s)
    capecitabine
    Intervention Type
    Drug
    Intervention Name(s)
    celecoxib
    Intervention Type
    Radiation
    Intervention Name(s)
    radiation therapy
    Intervention Type
    Procedure
    Intervention Name(s)
    surgery
    Primary Outcome Measure Information:
    Title
    Proportion of successes
    Time Frame
    Up to 5 years
    Secondary Outcome Measure Information:
    Title
    Survival time
    Time Frame
    Up to 5 years
    Title
    Time-to event analyses
    Time Frame
    Up to 5 years
    Title
    Time to disease progression/recurrence
    Time Frame
    Up to 5 years
    Title
    Time to recurrence
    Time Frame
    Up to 5 years
    Title
    Time to first progression
    Time Frame
    Up to 5 years
    Title
    Survival
    Time Frame
    Up to 5 years
    Title
    Bowel function as measured by the Patient Bowel Function (Uniscale) Questionnaire, the FACT Diarrhea Subscale and the Mayo Bowel Function Questionnaire
    Time Frame
    Up to 5 years

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility 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
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Frank Sinicrope, MD
    Organizational Affiliation
    Mayo Clinic
    Official's Role
    Study Chair

    12. IPD Sharing Statement

    Learn more about this trial

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

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