A Phase I-II Study of PAXG in Stage III-IV Pancreatic Adenocarcinoma
Conditions
Pancreatic Cancer
Conditions: official terms
Adenocarcinoma - Pancreatic Neoplasms
Conditions: Keywords
pancreatic adenocarcinoma, stage III disease, stage IV disease, chemotherapy
Study Type
Interventional
Study Phase
Phase 1/Phase 2
Study Design
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Intervention
Name: cisplatin Type: Drug
Name: capecitabine Type: Drug
Name: gemcitabine Type: Drug
Name: nab-paclitaxel Type: Drug
Overall Status
Recruiting
Summary
Four-drug combo yielded a statistically significant improvement in progression-free survival and overall survival compared to gemcitabine in patients with advanced pancreatic adenocarcinoma. Nab-Paclitaxel showed promising antitumor activity in patients with pancreatic cancer. Given the synergism of taxanes with gemcitabine, fluoropyrimidines and platinating agents the role of nab-Paclitaxel in a 4-drug regimen will be explored.

The aim of this trial is to determine the recommended dose of nab-paclitaxel in combination with cisplatin, capecitabine, and gemcitabine, PAXG regimen (Phase I), and to evaluate the feasibility and the activity of the PAXG regimen in patients with stage III and IV pancreatic cancer.
Detailed Description
OBJECTIVES: PHASE I: to determine the recommended phase 2 dose of nab-paclitaxel in combination with cisplatin, capecitabine, and gemcitabine.

PHASE II: to evaluate the feasibility and the activity of the PAXG regimen in terms of 6-months progression-free survival in patients with stage III and IV pancreatic cancer.

OUTLINE Phase I - dose finding single institution trial, followed by a randomized open label multicenter phase II trial.

Phase II: Patients will be stratified by stage (III vs IV) and CA19.9 level (< 10 x ULN versus >10 x ULN); Patients will be randomly assigned to receive PAXG (arm A) or gemcitabine-nab-paclitaxel regimen (arm B).

Treatment plan (phase II):

Arm A: PAXG every 4 weeks (1 cycle): cisplatin at 30 mg/m2 on days 1 and 15, nab-paclitaxel at the RP2D on days 1 and 15, capecitabine at 1250 mg/ m2 days 1-28, gemcitabine at 800 mg/ m2 on days 1 and 15.

Arm B: Gemcitabine + nab-paclitaxel every 4 weeks (1 cycle): gemcitabine at 1000 mg/m2 on days 1, 8 and 15; nab-paclitaxel at 125 mg/mq on days 1, 8 and 15.

Treatment will be administered for a maximum of 6 cycles or until there is a clinical benefit.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: 75 Years
Minimum Age: 18 Years
Gender: Both
Criteria: Inclusion Criteria:

- Pathologic diagnosis of pancreatic adenocarcinoma

- Stage III or IV disease

- Age > 17 < 76 years

- Karnofsky Performance Status > 50

- Measurable disease (only for phase II part)

- Adequate bone marrow (GB > 3500/mm3, neutrophils > 1500/mm3; platelets > 100000/mm3; hemoglobin > 10 g/dl), liver (total bilirubin < 2 mg/dL; SGOT e SGPT < 3 UNL) and kidney function (serum creatinin < 1.5 mg/dL;)

- Written informed consent

Exclusion Criteria:

- previous chemotherapy

- concurrent treatment with other experimental drugs

- previous or concurrent malignancies at other sites with the exception of surgically cured carcinoma in-site of the cervix and basal or squamous cell carcinoma of the skin and of other neoplasms without evidence of disease at least from 5 years

- symptomatic brain metastases

- history of interstitial lung disease

- presence of serious disease which can compromise safety (cardiac failure, previous myocardial infarction within the prior 6 months, cardiac arrhythmia, history of psychiatric disabilities)

- pregnancy and lactating

- History of connective tissue disorders (eg, lupus, scleroderma, arteritis nodosa).
Location
IRCCS S Raffaele
Milan, Italy
Status: Recruiting
Contact: Michele Reni, MD - +39 02 26437644 - reni.michele@hsr.it
Start Date
November 2012
Completion Date
December 2016
Sponsors
IRCCS San Raffaele
Source
IRCCS San Raffaele
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page