Combination of Oxaliplatin, Capecitabine, and Celecoxib With Concurrent Radiation for Rectal Cancer
Condition: Rectal Cancer
MeSH terms: Rectal Neoplasms
Intervention: Chemotherapy, Celecoxib, and Radiation
Intervention description: Enrolled rectal cancer patients are treated with concurrent chemoradiation and celecoxib pre-operatively for at least 14 days. Definitive surgery is performed within 6 weeks from the end of treatment.
Intervention MeSH terms: Celecoxib; Capecitabine; Oxaliplatin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 38.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Resectable Rectal Cancer; Radiation; Neoadjuvant; Rectum; GI - Colorectal Neoadjuvant; Cancer

Summary:

      A combination of chemotherapy and radiation is often used to treat rectal cancer patients
      before surgery in an effort to shrink the tumor and make it easier to remove as well as to
      help increase the chances of sphincter-sparing surgery. Many previous clinical studies have
      suggested that rectal cancer patients may survive longer if the surgery results in a
      pathological complete response - that is, the absence of any tumor cells in the surgical
      specimen. However, there is still controversy over this. This study attempts to start to
      answer this question by treating rectal cancer patients with a combination of chemotherapy
      drugs (oxaliplatin and capecitabine), a cyclooxygenase-2 (COX-2) enzyme inhibitor and
      radiation before surgery. The rates of pathologic complete response, sphincter-sparing
      surgery, and disease-free survival are some of the therapeutic endpoints that will be
      studied.
    

Eligibility criteria:

        Inclusion Criteria:

          -  All patients 18 years of age or older, with biopsy proven T3-4N0-2M0 rectal cancer are
             eligible.

          -  Life expectancy of at least 2 years.

          -  Zubrod performance status of 0-2.

          -  Patients must be able to sign an informed consent.

          -  Adequate bone marrow function: peripheral granulocyte count of > 1,500 cells/mm3 and
             platelet count >100,000/mm3, hemoglobin > 10 gm/dl and absence of a regular red blood
             cell transfusion requirement.

          -  Adequate hepatic function with a total serum bilirubin < 1.5 x ULN; alkaline
             phosphatase, alanine aminotransferase (ALAT), and aspartate aminotransferase (ASAT) <
             2.5 x the upper limit of normal (ULN); and adequate renal function as defined by a
             calculated creatinine clearance > 50 ml/min [Cockroft-Gault].

          -  Other initial cancer diagnosis more than five years ago without evidence of residual
             or recurrent disease

          -  Prior diagnosis of squamous or basal cell carcinoma of skin,no active disease at the
             time of enrollment.

        Exclusion Criteria:

          -  Known metastases

          -  Pregnant or lactating women. Women/men of childbearing potential not using a reliable
             and appropriate contraceptive method.

          -  May receive no other concurrent chemotherapy or radiation therapy during this trial.

          -  Severe medical problems such as uncontrolled diabetes mellitus or cardiovascular
             disease or active infections

          -  Prior pelvic radiation

          -  Known active inflammatory bowel disease, Crohn's disease or ulcerative colitis.

          -  Medical conditions that would preclude the patient from definitive surgery at the end
             of concurrent chemoradiation

          -  Serious, uncontrolled, concurrent infection(s).

          -  Prior severe reaction to fluoropyrimidine therapy, or known hyper-sensitivity to
             5-fluorouracil or known dihydropyrimidine dehydrogenase (DPD) deficiency.

          -  Treatment for other carcinomas within the last five years, except cured non-melanoma
             skin and treated in-situ cervical cancer.

          -  Participation in any investigational drug study within 4 weeks preceding the start of
             study treatment.

          -  Clinically significant cardiac disease or myocardial infarction within the last 12
             months.

          -  History of uncontrolled seizures, central nervous system disorders or psychiatric
             disability judged by the investigator to be clinically significant, precluding
             informed consent, or interfering with compliance of oral drug intake.

          -  Other serious uncontrolled medical conditions that the investigator feels might
             compromise study participation.

          -  Major surgery <4 weeks of the start of study treatment, without complete recovery.

          -  Lack of physical integrity of the upper gastrointestinal tract or malabsorption
             syndrome.

          -  Known, existing uncontrolled coagulopathy

          -  Any of the following laboratory values:

               -  Abnormal hematologic values (neutrophils < 1.5 x 10^9/L, platelet count < 100 x
                  10^9/L, hemoglobin < 10 gm/dl)

               -  Impaired renal function (estimated creatinine clearance <50 ml/min as calculated
                  with Cockroft-Gault equation.

               -  Serum total bilirubin > 1.5 x upper normal limit.

               -  ALAT, ASAT > 2.5 x upper normal limit (or > 5 x upper normal limit in the case of
                  liver metastases).

               -  Alkaline phosphatase > 2.5 x upper normal limit (or > 5 x upper normal limit in
                  the case of liver metastases or > 10 x upper normal limit in the case of bone
                  disease).

          -  Unwillingness to give written informed consent.

          -  Unwillingness to participate or inability to comply with the protocol for the duration
             of the study.

          -  History of allergic reactions, hypersensitivity reactions to aspirin, nonsteroidal
             anti-inflammatory drugs (NSAIDs), or sulfonamides