Nab-paclitaxel in Combination With Gemcitabine in Fragile Patients With Advanced Pancreatic Cancer

Study Overview
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Brief Summary
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In the list of cancer mortality by type of cancer pancreatic cancer ranks 4th in USA and the 6th in Europe. The estimated figures for 2010 in the USA were 42,000 new cases and 36,000 deaths from pancreatic cancer. The survival rate at 5 years after diagnosis is 4.6% in the USA. In Europe the figures are similar, with survival at 1, 3 and 5 years of 16%, 6% and 4%, respectively. Most patients are diagnosed in advanced stages that are no longer operable, so that treatment goals are often the prolongation of survival and palliation of symptoms. The aim of the study is to explore whether the new combination nab-paclitaxel plus gemcitabine is a therapeutic advance for this fragile population for which it is assumed that some modifications in dose and schedule of administration may be necessary in patients with good performance status. It is ultimately to find out the clinical benefit of this combination, but first making sure that dose and schedule of the combination are tolerable for these fragile patients. For this, the investigators have chosen a design that includes two stages: the first step aimed at choosing the safest treatment regimen for these patients among a group of treatment regimens used in other clinical trials. The second step will evaluate the effectiveness of the two regimens with the better results in the previous step.

Official Title
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Phase I/II Study to Assess the Efficacy and Safety of Nab-paclitaxel in Combination With Gemcitabine for the Treatment of Fragile Patients With Advanced or Metastatic Pancreatic Cancer

Conditions
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Advanced Pancreatic Cancer

Intervention / Treatment
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* Drug: Nab-paclitaxel 150 mg/m2 + Gemcitabine 1000 weeks 1,3/4
* Drug: Nab-paclitaxel 100 mg/m2 + Gemcitabine 1000 weeks 1,2,3/4
* Drug: Nab-paclitaxel 125 mg/m2 + Gemcitabine 1000 weeks 1,3/4
* Drug: Nab-paclitaxel 125 mg/m2 + Gemcitabine 1000 weeks 1,2,3/4


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who are 18 years or older; Patients with histological or, if not possible, cytologic confirmed adenocarcinoma of the pancreas. Patients with metastatic pancreatic cancer; Patient with an Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) = 2 Adequate hematopoietic, hepatic and renal function: Neutrophil count >= 1.5 x 10*9/L; Platelet count >= 100 x 10*9/L; Bilirubin <= 1.5 x ULN; AST and/or ALT <= 2.5 x ULN; Serum creatinine <= 1.5 x ULN. Investigators must ensure that patients enrolled in the study will be available for all study procedures, including tumor biopsy, chemotherapy treatment, and follow up. Investigators must ensure that patients have the ability to understand the requirements of the study and provide signed informed consent. Women of childbearing potential and men who wish to participate in the study must agree to use adequate contraception since the signing of informed consent until at least 3 months after stopping the study medication; Signed Informed Consent. Exclusion Criteria: Active or uncontrolled infections or serious illnesses or medical conditions that could interfere with patient eligibility for treatment; History of any psychiatric condition that might impair patient?s ability to understand or to comply with the requirements of the study or to provide informed consent; Concurrent anticancer therapy; Pregnant or breast-feeding women (documented methods of birth control are required in those with reproductive potential); History of allergic reactions attributed to compounds of similar chemical or biologic composition to study drugs; History of life threatening reaction to gemcitabine or abraxane; Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) <=1. Previous treatment with chemotherapy or chemoradiotherapy for advanced pancreatic cancer.

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 |
| --- | --- |
| Experimental: Arm B<br>Nab-paclitaxel 150 mg/m2 + Gemcitabine 1000 weeks 1,3/4 | Drug: Nab-paclitaxel 150 mg/m2 + Gemcitabine 1000 weeks 1,3/4<br>* Nab-paclitaxel 150 mg/m2 + Gemcitabine 1000 days 1 & 15 in a 28 days cycle<br>|
| Experimental: Arm C<br>Nab-paclitaxel 100 mg/m2 + Gemcitabine 1000 weeks 1,2,3/4 | Drug: Nab-paclitaxel 100 mg/m2 + Gemcitabine 1000 weeks 1,2,3/4<br>* Nab-paclitaxel 100 mg/m2 + Gemcitabine 1000 days 1,8 & 15 in a 28 days cycle<br>|
| Experimental: Arm D<br>Nab-paclitaxel 125 mg/m2 + Gemcitabine 1000 weeks 1,3/4 | Drug: Nab-paclitaxel 125 mg/m2 + Gemcitabine 1000 weeks 1,3/4<br>* Nab-paclitaxel 125 mg/m2 + Gemcitabine 1000 days 1 & 15 in a 28 days cycle<br>|
| Experimental: Arm E<br>Nab-paclitaxel 125 mg/m2 + Gemcitabine 1000 weeks 1,2,3/4 | Drug: Nab-paclitaxel 125 mg/m2 + Gemcitabine 1000 weeks 1,2,3/4<br>* Nab-paclitaxel 125 mg/m2 + Gemcitabine 1000 days 1,8 & 15 in a 28 days cycle<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PHASE I: To select the schemes with the best therapeutic indexes of the combination of gemcitabine and nab-paclitaxel in fragile patients with advanced pancreatic cancer. | Phase I: Therapeutic index. Criteria: Early mortality all causes at 30 and 60 days, Adverse Events grade 3 and 4, treatment discontinuation due to toxicity and relative dose intensity | Up to 2 months | 
| PHASE II: Evaluate the effectiveness of two selected schemes of gemcitabine and nab-paclitaxel, vs. gemcitabine alone. (Six months overall survival) | Six months overall survival | Up to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase I: evaluate safety profile of gemcitabine and nab-paclitaxel schemes. (Number of events per patient according to NCI-CTC-AE criteria) | Number of events per patient according to NCI-CTC-AE criteria | Up to 6 months | 
| Phase I: evaluate objective response rate. (Response rate will be evaluated according RECIST criteria) | Response rate will be evaluated according RECIST criteria | Up to 6 months | 
| Phase II: progression free survival (Time from randomization to disease progression according RECIST criteria) | Time from randomization to disease progression according RECIST criteria | Up to 8 months | 
| Phase II: objective response rate (Response rate will be evaluated according RECIST criteria) | Response rate will be evaluated according RECIST criteria | Up to 6 months | 
| Phase II: to explore changes induced by treatment on tumor Marker CA19.9 |  | Up to 8 months | 
| Phase II: change in FAP and Cav-1 tumor markers as an inidicatior of treatment efficacy |  | Up to 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Advanced pancreatic cancer, Fragile, Nab-paclitaxel