Capecitabine and Oxaliplatin in Patients With Advanced or Metastatic Pancreatic Adenocarcinoma

Phase 2

Completed

Conditions: Pancreatic Cancer

Interventions: Drug: Capecitabine
Drug: Oxaliplatin

Registration Number: NCT00585078

Lead Sponsor: Beth Israel Deaconess Medical Center

Brief Summary: There are limited treatment options available for patients with advanced pancreatic ductal adenocarcinoma (PDAC). The purpose of this study is to determine the effectiveness and safety of the drugs capecitabine and oxaliplatin in patients who have been diagnosed with advanced and metastatic PDAC treated in the first and second lines.

Detailed Description: OBJECTIVES:

Primary

* To determine the response rate to capecitabine and oxaliplatin in patients with locally advanced or metastatic pancreatic adenocarcinoma Secondary

* To determine safety

* To determine overall survival

* To determine time to progression

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 40

Inclusion Criteria

18 years of age or older
At most one prior chemotherapy regimen for unresectable or metastatic disease. Any adjuvant chemotherapy must have been completed more than 12 months prior to beginning protocol therapy
Histologically or cytologically confirmed adenocarcinoma of the pancreas
At least one measurable lesion according to RECIST criteria that has not been irradiated
Adequate laboratory parameters as outlined in protocol
Anticoagulation with coumadin is permitted, but PT/INR must be monitored closely, given the drug-drug interaction between coumadin and capecitabine
Negative serum pregnancy test within 14 days prior to registration

Exclusion Criteria

Pregnant or lactating women
Life expectancy < 3 months
Serious, uncontrolled, concurrent infection(s)
Any prior oxaliplatin or fluoropyrimidine therapy
More than one prior chemotherapy regimen for unresectable or metastatic disease
Prior unanticipated severe reaction to fluoropyrimidine therapy, or known sensitivity to 5-fluorouracil or platinum compounds
Any active second malignancy
Clinically significant cardiac disease or myocardial infarction within the last 12 months
Evidence of CNS metastases or history of uncontrolled seizures, central nervous system disorders or psychiatric disability
Other serious uncontrolled medical conditions
Major surgery within 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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
CAPOX	Capecitabine	Participants self-administered capecitabine 1,000 mg/m2 orally twice daily (total daily dose 2,000 mg/m2), days 1-14 in 21-day cycles. Only 500 mg tablets were used, and doses were rounded to the nearest dose that could be administered with 500 mg tablets. Oxaliplatin 130 mg/m2 was administered intravenously on day 1 every 21 (±2) days. Treatment continued until tumor progression or toxicity requiring discontinuation of therapy.
CAPOX	Oxaliplatin	Participants self-administered capecitabine 1,000 mg/m2 orally twice daily (total daily dose 2,000 mg/m2), days 1-14 in 21-day cycles. Only 500 mg tablets were used, and doses were rounded to the nearest dose that could be administered with 500 mg tablets. Oxaliplatin 130 mg/m2 was administered intravenously on day 1 every 21 (±2) days. Treatment continued until tumor progression or toxicity requiring discontinuation of therapy.

Primary Outcome Measures

Name	Time	Method
Response Rate	Response was assessed by computed tomography (CT) or magnetic resonance imaging (MRI) every two cycles (42 days ±2 days) on treatment. Participants received a median (range) of 2 cycles (1-12) of CAPOX.	Response rate (RR) is defined as the proportion of participants achieving partial response (PR) or complete response (CR) based on RECIST 1.0 criteria on treatment. Per RECIST 1.0 for target lesions, CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. To be assigned a status of CR or PR, changes in tumor measurements must be confirmed by repeat assessments performed no fewer than 4 weeks after the response criteria are first met. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.

Secondary Outcome Measures

Name	Time	Method
Overall Survival	Participants were followed long-term for survival every 3 months from the end of treatment until death or lost to follow-up. Median survival follow-up was 10.8 months (95% CI: 7.1-37.7) in this study cohort.	Overall survival is defined as the time from study entry to death or date last known alive and estimated using Kaplan-Meier (KM) methods.
Best Response	Response was assessed by computed tomography (CT) or magnetic resonance imaging (MRI) every two cycles (42 days ±2 days) on treatment. Participants received a median (range) of 2 cycles (1-12) of CAPOX.	Best response on treatment was based on RECIST 1.0 criteria: Complete Response (CR) is complete disappearance of all target lesions; Partial Response (PR) is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. Both require confirmation no fewer than 4 weeks apart. CR/PR assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions. Progressive disease (PD) is at least a 20% increase in the sum of longest diameter of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions. Stable disease is defined as any condition not meeting above criteria.
Progression-Free Survival	Disease evaluations occurred every two cycles (42 days ±2 days) on treatment. In this study cohort, participants were followed for progression up to 38 months.	Progression-free survival based on the Kaplan-Meier method is defined as the duration of time from study entry to documented disease progression (PD) requiring removal from treatment or death. Per RECIST 1.0 criteria: progressive disease (PD) is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions.