Erlotinib, Gemcitabine and Nab-Paclitaxel in Advanced Pancreatic Cancer

Study Overview
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Brief Summary
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This is a phase 1b study to evaluate the combination of gemcitabine and Tarceva (erlotinib) and nab-paclitaxel in patients with advanced pancreatic cancer.

Detailed Description
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This is a single-arm, phase 1b study to determine the maximum tolerated dose (MTD) of the combination of erlotinib (daily), gemcitabine (weekly), nab-paclitaxel (weekly) in patients with advanced pancreatic cancer.

Official Title
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A Phase Ib Study of Erlotinib in Combination With Gemcitabine and Nab-Paclitaxel in Patients With Previously Untreated Advanced Pancreatic Cancer

Conditions
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Advanced Pancreatic Cancer

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-1 Predicted life expectancy of >= 12 weeks Previous surgery Histologically or cytologically confirmed, measurable, locally advanced, unresectable or metastatic pancreatic adenocarcinoma No prior therapy for pancreatic cancer Adequate organ and marrow function Absolute neutrophil count >= 1.5 x 10^9/L Platelets >= 100 x 10^9/L Total bilirubin <= institutional upper limits of normal AST (SGOT)/ALT(SGPT) <= 2 x institutional upper limits of normal Serum creatinine <= 1.5 x upper limits of normal Negative pregnancy test Informed consent Patient must agree not to smoke while on study Exclusion Criteria: Significant history of cardiac disease unless the disease is well controlled Active or uncontrolled infections or serious illness or medical conditions that could interfere with the patient's ongoing participation in study History of any psychiatric condition that might impair the patient's ability to understand or to comply with the requirements of the study or to provide informed consent History of smoking within the previous 14 days before enrollment or positive cotinine test at baseline Pregnant or breast-feeding females Symptomatic brain metastases that are not stable, that require steroids, that are potentially life-threatening, or that have required radiation within the last 14 days History of allergic reactions attributed to compounds of similar chemical or biological composition to the study drugs

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: erlotinib, gemcitabine, nab-paclitaxel<br>Patients receive the following treatment in 28-day cycles: 1) erlotinib: orally once daily from days 1 through 28 continuous dosing; 2) gemcitabine (following nab-paclitaxel): intravenously over 30 minutes on days 1, 8 and 15 every 28 days; and 3) nab-paclitaxel: intravenously over 30 minutes on days 1, 8 and 15 every 28 days. | Drug: erlotinib<br>* administered orally<br>* Other names: OSI-774;Drug: gemcitabine<br>* administered intravenously<br>Drug: nab-paclitaxel<br>* administered intravenously<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dose |  | Monthly (to a maximum of 12 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of drug combination assessed through dose limiting toxicities (DLTs) |  | 1 month | 
| Safety of drug combination assessed through Adverse Events (AEs) |  | Monthly (to a maximum of 12 months) | 
| Evaluate erlotinib Pharmacokinetic (PK) trough concentrations (C24h) |  | Days 29 (Cycle 2, Day 1) and 30 | 
| Objective Response Rate | Response will be based on the RECIST v1.1 criteria. Patients with partial and complete response will be classified as responders. | Monthly (to a maximum of 12 months) | 
| Progression Free Survival (PFS) | PFS will be calculated as the time from start of treatment until disease progression or death; patients who are still alive and free of progression at their last follow-up will be censored at that time. | Monthly (to a maximum of 12 months) | 
| Overall Survival | Survival will be calculated as the time from start of treatment until death of any cause, patients who are still alive at their last follow-up will be censored at that time. | Monthly (to a maximum of 12 months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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erlotinib, nab-paclitaxel, gemcitabine, Adenocarcinoma, Advanced Pancreatic Cancer, Phase 1b