Nab-Pac+Cis+Gem in Pts w Previously Untreated Metastatic PDA

Study Overview
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Brief Summary
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The primary objective of this study is to determine the efficacy of nab-paclitaxel plus cisplatin plus gemcitabine for patients with metastatic pancreatic ductal adenocarcinoma (PDA).

Detailed Description
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This is a phase 1b/2 open-label pilot study evaluating the preliminary efficacy and safety of nab-paclitaxel, cisplatin, and gemcitabine in patients with metastatic pancreatic ductal adenocarcinoma. An individual cycle of therapy will be defined as Days 1 and 8 every 21 days. Multiple cycles may be administered until the patient is withdrawn from therapy. Overall response rates as well as individual categories of response (complete response-CR, partial response-PR, stable disease-SD and progressive disease-PD) will be determined using RECIST 1.1. Time-to-event endpoints, including progression free survival (PFS) and OS (overall survival) will be assessed using the Kaplan-Meier method. Evaluation of stable disease at 9 weeks will also be assessed. Toxicity (adverse events) will be recorded using the NCI CTCAE (v4.0, May 2009).

Official Title
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A Phase 1b/2 Pilot Trial of Nab-Paclitaxel Plus Cisplatin Plus Gemcitabine (Nabplagem) in Patients With Previously Untreated Metastatic Pancreatic Ductal Adenocarcinoma (PDA)

Conditions
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Stage IV Pancreatic Cancer

Intervention / Treatment
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* Drug: nab-paclitaxel
* Drug: Cisplatin
* Drug: gemcitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age >18 years of age; male or female. Histologically or cytologically confirmed metastatic pancreatic ductal adenocarcinoma. Capable of providing informed consent and complying with trial procedures. Karnofsky Performance Status (KPS) of >/=70%. Life expectancy >/=12 weeks. Measurable tumor lesions according to RECIST 1.1 criteria. Women must not be able to become pregnant (e.g. post-menopausal for at least 1 year, surgically sterile, or practicing adequate birth control methods) for the duration of the study. Women of child bearing potential must have a negative serum or urine pregnancy test at the Screening Visit and be non-lactating. Both male and female patients of reproductive potential must agree to use a reliable method of birth control during the study. Exclusion Criteria: Patients must have received no previous radiotherapy, surgery, chemotherapy or investigational therapy for the treatment of metastatic disease. Prior treatments in the adjuvant setting with gemcitabine and/or 5-FU or gemcitabine administered as a radiation sensitizer are allowed, provided at least 6 months have elapsed since completion of the last dose and no lingering toxicities are present. Palliative surgery and/or radiation treatment less than 4 weeks prior to initiation of study treatment. Exposure to any investigational agent within 4 weeks prior to initiation of study treatment. Evidence of central nervous system (CNS) metastasis (negative imaging study, if clinically indicated, within 4 weeks of Screening Visit). History of other malignancies (except cured basal cell carcinoma, superficial bladder cancer or carcinoma in situ of the cervix) unless documented free of cancer for >/= 5 years. Laboratory values: Screening serum creatinine > upper limits of normal (ULN); total bilirubin > ULN: alanine aminotransferase (ALT) and AST >/= 2.5 ULN or >/= 5.0 x ULN if liver metastases are present; absolute neutrophil count < 1,500/mm3, platelet concentration < 100,00/mm3, hematocrit level < 27% for females or < 30% for males, or coagulation tests (prothrombin time [PT], partial thromboplastin time [PTT], International Normalized Ratio [INR]) > 1.5 x ULN unless on therapeutic doses of warfarin. current, serious, clinically significant cardiac arrhythmias as determined by the Investigator. History of HIV infection. Active, clinically significant serious infection requiring treatment with antibiotics, anti-virals or anti-fungals. Major surgery within 4 weeks prior to initiation of study treatment. Any condition that might interfere with the patient's participation in the study or in the evaluation of the study results. Any condition that is unstable and could jeopardize the patient's participation in the study.

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: nab-paclitaxel+Cisplatin+gemcitabine<br>This is a phase Ib/II open-label, pilot study evaluating the preliminary efficacy and safety of nab-paclitaxel 125mb/m2, cisplatin 25mg/m2, and gemcitabine 1000mg/m2, all administered intravenously (IV) on Days 1 and 8 every 21 days until development of toxicity that is unacceptable in the opinion of the patient or the Investigator or upon disease progression. | Drug: nab-paclitaxel<br>* 25 mg/m2 given intravenously (IV) on days 1 and 8 of a 21 day cycle<br>* Other names: Abraxane;Drug: Cisplatin<br>* 25mg/m2 (or 50mg/m2) given intravenously (IV) on days 1 and 8 of a 21 day cycle<br>* Other names: CDDP;Drug: gemcitabine<br>* 1000mg/m2 given intravenously (IV) on days 1 and 8 of a 21 day cycle<br>* Other names: Gemzar;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Response Rate | The primary objectives of this study is to pursue treatment of 25 individual patients with previously untreated metastatic pancreatic ductal adenocarcinoma (PDA) to evaluate: Complete response rate as defined by computed tomography (CT) scan using RECIST 1.1 criteria and CA 19-9 (or CA 125, or CEA if not expressers of CA 19-9) down to normal limits (from at least > 2x ULN). We expect to accomplish this in > or = to 5% of patients. When a complete response (CR) is documented, a confirmatory PET scan will be obtained. If 1 or more of 10 patients demonstrate a complete response (CR), study will continue to enroll to a total of 25 patients. If intolerable adverse events or no clinical benefit are noted in the first 6 patients, study will discontinue enrollment. | 1 yr. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment-Related Toxicities | Frequency of treatment-related toxicities | Over the course of the subjects' treatment on study, approx 1 year | 
| Percentage Change in CA 19-9 | Percentage change in CA 19-9 from baseline values | Over the course of the subjects' treatment on study, approx 1 year | 
| Overall Survival | Overall survival is defined as the time from study enrollment until death from any cause. | Over the course of the subjects' treatment and participation in study, approx 18 mos | 
| Progression-Free Survival | Progression-free survival is defined as the time from study enrollment until the first documented tumor progression (using RECIST 1.1 criteria) or death from any cause. | Over the course of the subjects' treatment and participation in study, approx 18 mos | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pancreatic cancer, pancreatic adenocarcinoma, Stage IV pancreatic cancer, pancreas, pancreatic