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Celecoxib/Oxaliplatin/Capecitabine for Gastric/Gastroesophageal Junction Carcinoma

Primary Purpose

Gastric Carcinoma, Gastroesophageal Junction Carcinoma

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Oxaliplatin
Capecitabine
Celecoxib
Sponsored by
University of California, Irvine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Gastric Carcinoma focused on measuring Gastric Carcinoma, Gastroesophageal junction Carcinoma

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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]

Sites / Locations

  • Chao Family Comprehensive Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Celecoxib/Oxaliplatin/Capecitabine

Arm Description

Oxaliplatin 70mg/m2 IV on Days 1 and 8. Capecitabine 1000mg/m2 PO BID from Days 1 through 14. Celecoxib 400mg PO BID from Days 1 through 21. 1 Cycle = 21 days.

Outcomes

Primary Outcome Measures

Response rate of patients with gastric/gastroesophageal carcinoma when treated with celecoxib, oxaliplatin, and capcetabine combination therapy
Complete Response (CR) Complete disappearance of all measurable and evaluable disease. No new lesions. No disease related symptoms. No evidence of non evaluable disease, including normalization of markers and other abnormal lab values. All measurable, evaluable and non evaluable lesions and sites must be assessed using the same techniques as baseline. Partial Response (PR): Applies only to patients with at least one measurable lesion. Greater than or equal to 50% decrease under baseline in the sum of products of perpendicular diameters of all measurable lesions. No progression of evaluable disease. No new lesions. All measurable and evaluable lesions and sites must be assessed using the same techniques as baseline. A response rate (RR) is defined as a complete or partial response. RR=CR+PR
Determine time to progression
Progression: 50% increase or an increase of 10 CM2 (whichever is smaller) in the sum of products of all measurable lesions over smallest sum observed (over baseline if no decrease) using the same techniques as baseline, or clear worsening of any evaluable disease, or reappearance of any lesion which had disappeared, or appearance of any new lesion/site, or failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer). For "scan only" bone disease, increased uptake does not constitute clear worsening. Worsening of existing non evaluable disease does not constitute progression.

Secondary Outcome Measures

Incidence of treatment-related study adverse events and toxicity according to NCI Common Toxicity Criteria v2.X
Toxicity and adverse events are graded on CTC (NCI Common Toxicity Criteria) version 2.X.
Evaluate the expression of the Cox-2 on paraffin-embedded tumor sections from patients enrolled on the study and correlate expression with clinical response

Full Information

First Posted
November 18, 2005
Last Updated
February 6, 2019
Sponsor
University of California, Irvine
Collaborators
Sanofi-Synthelabo
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1. Study Identification

Unique Protocol Identification Number
NCT00256321
Brief Title
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

2. Study Status

Record Verification Date
February 2019
Overall Recruitment Status
Terminated
Why Stopped
Closed due to poor accrual
Study Start Date
October 2004 (undefined)
Primary Completion Date
August 2007 (Actual)
Study Completion Date
August 2007 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of California, Irvine
Collaborators
Sanofi-Synthelabo

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gastric Carcinoma, Gastroesophageal Junction Carcinoma
Keywords
Gastric Carcinoma, Gastroesophageal junction Carcinoma

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
Celecoxib/Oxaliplatin/Capecitabine
Arm Type
Experimental
Arm Description
Oxaliplatin 70mg/m2 IV on Days 1 and 8. Capecitabine 1000mg/m2 PO BID from Days 1 through 14. Celecoxib 400mg PO BID from Days 1 through 21. 1 Cycle = 21 days.
Intervention Type
Drug
Intervention Name(s)
Oxaliplatin
Other Intervention Name(s)
Eloxatin
Intervention Description
Oxaliplatin 70mg/m2 IV on Days 1 and 8
Intervention Type
Drug
Intervention Name(s)
Capecitabine
Other Intervention Name(s)
Xeloda
Intervention Description
Capecitabine 1000mg/m2 PO BID from Days 1 through 14.
Intervention Type
Drug
Intervention Name(s)
Celecoxib
Other Intervention Name(s)
Celebrex
Intervention Description
Celecoxib 400mg PO BID from Days 1 through 21.
Primary Outcome Measure Information:
Title
Response rate of patients with gastric/gastroesophageal carcinoma when treated with celecoxib, oxaliplatin, and capcetabine combination therapy
Description
Complete Response (CR) Complete disappearance of all measurable and evaluable disease. No new lesions. No disease related symptoms. No evidence of non evaluable disease, including normalization of markers and other abnormal lab values. All measurable, evaluable and non evaluable lesions and sites must be assessed using the same techniques as baseline. Partial Response (PR): Applies only to patients with at least one measurable lesion. Greater than or equal to 50% decrease under baseline in the sum of products of perpendicular diameters of all measurable lesions. No progression of evaluable disease. No new lesions. All measurable and evaluable lesions and sites must be assessed using the same techniques as baseline. A response rate (RR) is defined as a complete or partial response. RR=CR+PR
Time Frame
18 weeks
Title
Determine time to progression
Description
Progression: 50% increase or an increase of 10 CM2 (whichever is smaller) in the sum of products of all measurable lesions over smallest sum observed (over baseline if no decrease) using the same techniques as baseline, or clear worsening of any evaluable disease, or reappearance of any lesion which had disappeared, or appearance of any new lesion/site, or failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer). For "scan only" bone disease, increased uptake does not constitute clear worsening. Worsening of existing non evaluable disease does not constitute progression.
Time Frame
18 weeks
Secondary Outcome Measure Information:
Title
Incidence of treatment-related study adverse events and toxicity according to NCI Common Toxicity Criteria v2.X
Description
Toxicity and adverse events are graded on CTC (NCI Common Toxicity Criteria) version 2.X.
Time Frame
18 weeks
Title
Evaluate the expression of the Cox-2 on paraffin-embedded tumor sections from patients enrolled on the study and correlate expression with clinical response
Time Frame
18 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
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]
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Randall Holcombe, MD
Organizational Affiliation
Chao Family Comprehensive Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Chao Family Comprehensive Cancer Center
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States

12. IPD Sharing Statement

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Celecoxib/Oxaliplatin/Capecitabine for Gastric/Gastroesophageal Junction Carcinoma

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