Second Line Chemotherapy for Advanced Pancreatic Cancer

Study Overview
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Brief Summary
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No validated second-line chemotherapy for the treatment of locally advanced/metastatic pancreatic cancer is actually available,after the failure of a gemcitabine(+/- Cisplatin or Oxaliplatin)-based regimen. Irinotecan seems to be a moderately active drug in the treatment of this disease Recently was reported some interesting results using a potentially non -cross resistant regimen (FOLFIRI) which could be useful even as second-line chemotherapy. An exploratory study in this setting seem warranted.

Official Title
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Folfiri as Second-Line Chemotherapy for Advanced Pancreatic Cancer. A GISCAD Phase II Study

Conditions
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Pancreatic Adenocarcinoma

Intervention / Treatment
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* Drug: FOLFIRI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed written informed consent prior to beginning protocol specific procedures Previous chemotherapy with Gemcitabine plus or less Platinoids Previous gemcitabine delivered as a radiosensitizer for locally advanced disease, followed or not by a gemcitabine plus or less platinoids as maintenance or disease progression is allowed. Male or female less than 75 years of age Diagnosis of histologically or cytologically confirmed adenocarcinoma of the pancreas Locally advanced (non-resectable) or metastatic pancreatic cancer Presence of at least one uni-dimensional indicator lesion measurable by CT scan or MRI in not an irradiated area ECOG performance status 0 to 1 at study entry Life expectancy: more than 3 months Neutrophils more than 1.5 x 109L, platelets more than 100 x 109L, and hemoglobin more than 10 gdL Bilirubin level either normal or less than 1.5 x ULN ASAT and ALAT normal or less than 2.5 x ULN (normal or less than 5 x ULN if liver metastasis are present) Serum creatinine less than 1.5 x ULN Amylase normal or less than 1.5 ULN Effective contraception for both male and female patients if the risk of conception exists Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be assessed with the patient before registration in the trial Exclusion Criteria: Brain metastases Previous treatment with irinotecan or fluoropyrimidines Significant cardiovascular disease: clinically relevant coronary artery disease or a history of a myocardial infarction within the last 6 months Significant gastrointestinal abnormalities Gilbert's Syndrome Any uncontrolled infections Known HIV infection Radiotherapy within 4 weeks prior to study entry Any investigational agents 4 weeks prior to entry Known grade 3 or 4 allergic reaction to any of the components of the treatment Known drug abuse or alcohol abuse Medical or psychological condition which in the opinion of the investigator would not permit the patient to complete the study or sign meaningful informed consent Women who are pregnant or breastfeeding Any concurrent malignancy other than non-melanoma skin cancer, or carcinoma in situ of the cervix. Legal incapacity or limited legal capacity

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FOLFIRI<br>Folfiri consist of Irinotecan 180 mg/m2 iv on day 1, Leucovorin(l-form) 200 mg/m2 iv on day 1and 2, 5-FU 400 mg/m2 iv bolus on day 1and 2, 5-FU 600 mg/m2 iv by ci for 22 hours on day 1 and 2, repeated every 2 wks The use of antiemetic prophylaxis was decided locally. | Drug: FOLFIRI<br>* Irinotecan 180 mg/m2 iv on day 1, Leucovorin(l-form) 200 mg/m2 iv on day 1,2 5-FU 400 mg/m2 iv bolus on day 1,2 5-FU 600 mg/m2 iv by ci for 22 hrs on day 1,2 repeated every 2 wks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (RECIST Criteria) | time from randomization date to date of death from any cause | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability; Safety (CTC criteria - version 3.0) | Treatment will consist of 4 combination-chemotherapy cycles and in case of stable or responsive disease, other 4 cycles can be administered at investigator's discretion. Therefore will be administered for up to 6 months Each treatment cycle will consist of 2 weeks, unless the start of the subsequent cycle is delayed, in which case the cycle length will be longer than 4 weeks. | 18 months | 
| Overall survival (OS) | OS is calculated using the Kaplan-Meyer method The principal objective of the trial is to assess the therapeutic activity of FOLFIRI in patients with exocrine pancreas carcinoma. The primary activity parameter to be determined is overall response rate. | time from first cycle to death | 
| Progression Free Survival | PFS was calculated using the Kaplan-Meyer method Presence of at least one target lesion measurable by CT scan or MRI in not an irradiated area (and conform with the RECIST criteria) | time from first cycle to progression or death | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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FOLFIRI, Metastases, pancreatic adenocarcinoma, locally advanced or metastatic pancreatic adenocarcinoma