A Phase I-II Study of PAXG in Stage III-IV Pancreatic Adenocarcinoma (PACT-19)

San Donato Group (GSD)

Status and phase: Completed; Phase 2; Phase 1

Conditions: Pancreatic Cancer

Treatments: Drug: nab-paclitaxel; Drug: capecitabine; Drug: cisplatin; Drug: gemcitabine

Study type: Interventional

Funder types: Other

Identifiers

NCT01730222

PACT-19

2012-001763-75 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 137 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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137 participants in 2 patient groups

PAXG regimen

Experimental group

Description:

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 every 4 weeks

Treatment:

Drug: gemcitabine

Drug: cisplatin

Drug: capecitabine

Drug: nab-paclitaxel

gemcitabine + nab-paclitaxel

Active Comparator group

Description:

gemcitabine at 1000 mg/ m2 on days 1, 8 and 15 every 4 weeks + nab-paclitaxel at 125 mg/ m2 on days 1, 8 and 15 every 4 weeks

Treatment:

Drug: gemcitabine

Drug: nab-paclitaxel