Clinical trial NCT00256321: Celecoxib/Oxaliplatin/Capecitabine for Gastric/Gastroesophageal Junction Carcinoma
Official title: A Phase II Study of Celecoxib/Oxaliplatin/Capecitabine Combination Chemotherapy for Unresectable,Recurrent, or Metastatic Gastric/Gastroesophageal Junction Carcinoma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Gastric Carcinoma
Gastroesophageal Junction Carcinoma
Keywords: Gastric Carcinoma
Gastroesophageal junction Carcinoma
Lead sponsor: University of California, Irvine
Sponsor class: OTHER
Collaborators: name: Sanofi-Synthelabo
First posted: 2005-11-21
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Gastric cancer is the second most common neoplasm in the world. Early diagnosis and surgical resection improve the survival and the chance of cure. Unfortunately, majority of cases are diagnosed at advanced stage, with only 20% of the patients presenting with localized disease. The five-year survival for gastric cancer of all stages remains at a dismal 8%. Chemotherapy has been used for advanced gastric cancer but with unsatisfactory results. Therefore, new approaches are needed for these patients. Among the newer chemotherapy regimens for advanced gastric cancer include a combination of oral 5-Fluoro-Uracil (FU)-based compound called Capecitabine(Xeloda) and Oxaliplatin. A few phase II studies suggest that the combination regimen is active with overall response rates ranging 30-40%. Several preclinical and clinical studies have shown that the expression of cyclooxygenase enzyme II(COX-2) is upregulated in many pre-neoplastic and neoplastic lesions. Furthermore, there appears to be an association with the overexpression of Cox-2 and the invasiveness of cancer and prognosis. Finally, preclinical and clinical studies suggest selective Cox-2 inhibitors can induce apoptosis in gastric cancer cells and retard tumor progression. Therefore, there is a strong rationale for the combination of a selective Cox-2 inhibitor, Celecoxib, with Capecitabine and Oxaliplatin in a therapeutic phase II trial for patients with advanced or recurrent gastric cancer.


Eligibility criteria: Inclusion Criteria:

* Patient must have histologically proven, pathologically verified and surgically incurable(unresectable, recurrent, or metastatic) gastric/gastroesophageal junction carcinoma. Gastric lymphoma and Gastrointestinal stromal tumor(GIST) are ineligible for this study. At least 6 unstained paraffin-embedded pathologic specimen slides will be required for the COX-2 expression assays.
* Patient must have bidimensionally measurable disease as defined below. Measurable lesions must be assessed (by physical examination, CT scan, radionuclide scan or plain X-ray) within 30 days prior to registration. The patient's disease status must be completely assessed and reported.

(Measurable Disease: Bidimensionally measurable lesions with clearly defined margins by: 1) Ruler measurement or medical photograph (skin or oral lesion), or plain x ray with at least one diameter .5 cm or greater (bone lesions are not included) or, 2) CT, MRI or other imaging scan with both diameters greater than the distance between cuts of the imaging study, or 3) palpation with both diameters 2 cm or greater.)

* All patients must undergo a CT of abdomen and chest within 30 days prior to registration.
* Patients may have received prior radiation therapy. Radiation therapy must have been completed at least 30 days before registration.
* Patients may have received prior surgery. Prior surgery must have been completed at least 30 days before registration.
* Performance status must be 0-2 according to Southwest Oncology Group Criteria

Exclusion criteria:

* Patients with brain metastases are NOT eligible for this study. It is not mandatory to obtain brain CT or MRI on all patients. However, patients who exhibit neurological symptoms or have pulmonary metastases on radiographic studies must obtain brain CT w/ IV contrast or MRI prior to registration to ascertain the presence of brain metastasis.
* Patients must NOT have received capecitabine or oxaliplatin. Prior use of cisplatin, carboplatin, 5-FU are permitted. Prior systemic therapy must have been completed at least 30 days before registration.
* Pregnant or nursing women are not eligible to participate in this trial because the safe use of these drugs in pregnancy have not been established. Urine pregnancy test must be done prior to the study.
* Patient must NOT have known allergic reaction to sulfonamides
* Patient must NOT have known allergic or other adverse reaction to celecoxib
* Patient must NOT have persistent peripheral neuropathy
* Patient must NOT have known hypersensitivity reactions to 5-FU or platinum
* Patient must NOT have active gastric/duodenal bleeding
* Patient must NOT have had a sensitivity reaction to aspirin or other NSAIDS nonsteroidal antiinflammatory drugs (NSAIDS) \[experiencing asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs\]

Primary outcomes:
measure: Response rate of patients with gastric/gastroesophageal carcinoma when treated with celecoxib, oxaliplatin, and capcetabine combination therapy
timeFrame: 18 weeks
measure: Determine time to progression
timeFrame: 18 weeks
Secondary outcomes:
measure: Incidence of treatment-related study adverse events and toxicity according to NCI Common Toxicity Criteria v2.X
timeFrame: 18 weeks
measure: Evaluate the expression of the Cox-2 on paraffin-embedded tumor sections from patients enrolled on the study and correlate expression with clinical response
timeFrame: 18 weeks
Other outcomes:
Locations:
city: Orange
country: United States
facility: Chao Family Comprehensive Cancer Center
state: California
Study officials:
affiliation: Chao Family Comprehensive Cancer Center
name: Randall Holcombe, MD
role: PRINCIPAL_INVESTIGATOR
References: