Abraxane and Gemcitabine Versus Gemcitabine Alone in Locally Advanced Unresectable Pancreatic Cancer.

Study Overview
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Brief Summary
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Pancreatic cancer is the fourth cause of cancer mortality: there are different treatment approaches to locally advanced pancreatic cancer management. Generally, gemcitabine alone is considered a reasonable approach for advanced pancreatic cancer patients but we need a chemotherapeutic regimen able to prevent as much as possible a progression of the disease. Nab-paclitaxel (Abraxane) recently demonstrated an interesting activity profile in advanced pancreatic cancer. A combination of Nab-paclitaxel and gemcitabine has been demonstrated superior to gemcitabine alone in metastatic patients.

Detailed Description
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Study population: Locally advanced unresectable pancreatic cancer patients Elegibility criteria: Written informed consent Age >18 < 75 years Histologically/cytologically confirmed locally advanced, unresectable pancreatic cancer At least one lesion measurable with CT or MRI scan Performance Status (ECOG) 0-1 at study entry Life expectancy of at least 3 months Adequate marrow, liver and renal function Effective contraception if the risk of conception exists (in the Informed Consent for the patients the descriptions of possible contraceptives is reported

Official Title
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A Phase II Randomized Trial Comparing a Combination of Abraxane and Gemcitabine Versus Gemcitabine Alone as First Line Treatment in Locally Advanced Unresectable Pancreatic Cancer. GAP (Gemcitabine Abraxane Pancreas) Trial

Conditions
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Pancreatic Cancer Stage II

Intervention / Treatment
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* Drug: Nab-paclitaxel and Gemcitabine
* Drug: Gemcitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent Age >18 < 75 years Histologically/cytologically confirmed locally advanced, unresectable pancreatic cancer At least one lesion measurable with CT or MRI scan Performance Status (ECOG) 0-1 at study entry Life expectancy of at least 3 months Adequate marrow, liver and renal function Effective contraception if the risk of conception exists (in the Informed Consent for the patients the descriptions of possible contraceptives is reported) Exclusion Criteria: Previous chemotherapy or radiotherapy for pancreatic cancer Severe cardiovascular disease Thrombotic or embolic events Acute or subacute intestinal occlusion or history of inflammatory bowel disease Known hypersensitivity to study drug Known drugs or alcohol abuse Pregnant or breastfeeding women Previous or concurrent malignancy; except for basal or squamous cell skin cancer and/or in situ carcinoma of the cervix, or other solid tumors treated curatively and with evidence of no recurrence for at least 5 years prior to randomization Unable to sign informed consent

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: nab-paclitaxel and gemcitabine<br>ARM A: nab-paclitaxel 125 mg/mq over 30 min and gemcitabine 1000 mg/mq weekly on days 1, 8 and 15 of a 28-day cycle | Drug: Nab-paclitaxel and Gemcitabine<br>* Chemotherapy will consist of nab-paclitaxel 125 mg/mq over 30 min and gemcitabine 1000 mg/mq weekly on days 1, 8 and 15 of a 28-day cycle<br>* Other names: gemzar;Drug: Gemcitabine<br>* gemcitabine 1000 mg/mq over 30 minutes on days 1, 8 and 15 of a 28-day cycle.<br>* Other names: gemzar;|
| Active Comparator: Gemcitabine<br>ARM B: Gemcitabine 1000 mg/mq over 30 minutes on days 1, 8 and 15 of a 28-day cycle. | Drug: Gemcitabine<br>* gemcitabine 1000 mg/mq over 30 minutes on days 1, 8 and 15 of a 28-day cycle.<br>* Other names: gemzar;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Rate | Assuming an expected progression rate in the control arm of 40% and an auspicated progression rate in the experimental arm of 20%,with one-tailed alpha=0.05, 80% power, 124 patients are required for the final analysis | progression rate is evaluated after 3 cycles of chemotherapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of Response | All patients must be considered in response analysis, including those who discontinue treatment or who die for any reason prior to response evaluations | Response to treatment is evaluated according to the RECIST criteria at the end of chemotherapy | 
| Esplore the effects of nab-paclitaxel in terms of toxicity | Treatment-emergent adverse events, drug-related adverse events and safety laboratory parameters will be analysed by treatment groups and CTCAE grade | every 3 cycles of chemotherapy | 
| Progression Free Survival | Progression free survival time will be defined as the time from randomization until the date of first observed disease progression (radiological or clinical, whichever is earlier) or death due to any cause, if death occurs before progression is documented. Patients who did not progress will be censored at the last date they were known to be alive. Patients who died of disease and for whom a date of progression is not available will be considered to have progressed on the day of their death | time from the start of the treatment until PD or death | 
| Overall Survival | Overall survival time will be defined as the time from randomization to the date of death. If the subject has not died, survival will be censored on the last date the subject was known to be alive (last date of follow up). | the time from randomization to the date of death | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pancreatic cancer, locally advanced, unresectable cancer