Phase I/II Study of Nab-paclitaxel and Gemcitabine Followed by AG-mFOLFOX in Patients With Metastatic Pancreatic Adenocarcinoma

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety and efficacy of nab-paclitaxel (Abraxane) and gemcitabine followed by modified FOLFOX (AG-mFOLFOX) in patients with previously untreated, metastatic pancreatic adenocarcinoma

Official Title
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A Phase I/II Study of Nab-paclitaxel (Abraxane) and Gemcitabine Followed by Modified FOLFOX (AG-mFOLFOX) in Patients With Previously Untreated, Metastatic Pancreatic Adenocarcinoma

Conditions
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Metastatic Pancreatic Adenocarcinoma

Intervention / Treatment
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* Drug: nab-paclitaxel
* Drug: gemcitabine
* Drug: m-FOLFOX
* Drug: nab-paclitaxel
* Drug: gemcitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically and/or cytologically confirmed pancreatic adenocarcinoma Stage IV disease (metastatic only) No prior systemic therapy for their diagnosis (except in adjuvant/neoadjuvant setting>six months previously) ECOG performance status of 0-1 At least 18 years of age Evidence of either or both of the following RECIST-defined measurable disease (lesions that can be accurately measured in at least one dimension with the longest diameter ≥ 20mm using conventional techniques or ≥10 mm with spiral CT scan) Female patients must be either surgically sterile or postmenopausal, or if of childbearing potential must have a negative pregnancy test (serum or urine) prior to enrollment and agree to use effective barrier contraception during the period of therapy. Oral, implantable, or injectable contraceptives may be affected by cytochrome P450 interactions, and are therefore not considered effective for this study. Male patients must be surgically sterile or must agree to use effective contraception during the period of therapy. The definition of effective contraception will be based on the judgment of the investigator. Adequate bone marrow function: ANC ≥ 1500/uL platelet count ≥ 100,000/uL hemoglobin ≥ 9.0 g/dL Adequate hepatic function: Total bilirubin ≤ 1.5 X ULN AST (SGOT) ≤ 2.5 X ULN ALT (SGPT) ≤ 2.5 X ULN Adequate renal function as determined by either: - Calculated or measured creatinine clearance ≥ 40 mL/min (for calculated creatinine clearance, Cockroft-Gault equation will be used). Ability to understand the nature of this study protocol and give written informed consent. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures. Exclusion Criteria: History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that, in the opinion of the investigator, renders the subject at high risk from treatment complications or might affect the interpretation of the results of the study. Presence of central nervous system or brain metastases. Life expectancy < 12 weeks Pregnancy (positive pregnancy test) or lactation. Pre-existing sensory neuropathy > grade 1. Clinically significant cardiac disease (e.g. congestive heart failure, symptomatic coronary artery disease and cardiac arrhythmias not well controlled with medication) or myocardial infarction within the last 12 months. Major surgery and/or radiotherapy within 4 weeks of the start of study treatment, without complete recovery. Prior malignancy except for adequately treated basal cell skin cancer, in situ cervical cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission, or any other form of cancer from which the patient has been disease-free for 5 years.

Ages Eligible for Study
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Minimum Age: 18 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: AG<br>nab-Paclitaxel followed by Gemcitabine | Drug: nab-paclitaxel<br>* Day 1-8-15: Intravenous, 125 mg/m2 over 30 minutes<br>Drug: gemcitabine<br>* Day 1-8-15: Intravenous, 1.000 mg/m2 over 30 minutes<br>|
| Experimental: AG-mFOLFOX<br>nab-Paclitaxel followed by Gemcitabine and FOLFOXm at dose levels selected from the phase I trial | Drug: m-FOLFOX<br>* Day 28 according to the dose levels stablished in Phase I<br>Drug: nab-paclitaxel<br>* Day 1-8-15: Intravenous 30 minutes according to the dose levels stablished in Phase I<br>Drug: gemcitabine<br>* Day 1-8-15: Intravenous 30 minutes according to the dose levels stablished in Phase I<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-limiting toxicity for the AG-mFOLFOX combination | Primary outcome phase I. | 12 weeks | 
| Rate of overall survival al 12 months | Primary outcome phase II | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of overall survival at 6 months |  | 54 months | 
| Rate of overall survival at 24 months |  | 54 months | 
| Time to tumor progression |  | 54 months | 
| Progression free survival |  | 54 months | 
| Overall Survival |  | 54 months | 
| Objective radiographic response | Secondary outcome Phase I and Phase II | 54 months | 
| CA 19-9 biomarker response |  | 54 months | 
| Safety profile of this combination (AG-mFOLFOX) using NCI-CTCAE v.4 criteria | Secondary outcome Phase I and Phase II | 54 months | 
| To assess the Quality of Life of the patients through the EORTC QLQ-C30/PAN26 and EORTC QLQ-CIPN20 questionnaires | Secondary outcome Phase I and Phase II | 54 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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metastatic pancreatic adenocarcinoma, Nab-paclitaxel, Gemcitabine, modified FOLFOX