Clinical trial NCT01730222: A Phase I-II Study of PAXG in Stage III-IV Pancreatic Adenocarcinoma
Official title: A Phase I-II Study of PAXG in Stage III-IV Pancreatic Adenocarcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Pancreatic Cancer
Keywords: pancreatic adenocarcinoma
stage III disease
stage IV disease
chemotherapy
Lead sponsor: IRCCS San Raffaele
Sponsor class: OTHER
First posted: 2012-11-21
Enrollment: 137
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Eligibility 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).

Primary outcomes:
measure: first cycle toxicity for phase I part
timeFrame: after one month from treatment start
measure: progression-free survival for phase II part, stage IV patients
timeFrame: after 6 months from randomization
measure: resectability rate for phase II part, stage III patients
timeFrame: after 4 and 6 months from treatment start
Secondary outcomes:
measure: response rate
timeFrame: every two months up to 6 months during treatment; every 2-3 months afterwards until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months
measure: biochemical response rate
timeFrame: every month up to 6 months during treatment; every 2-3 months afterwards until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months
measure: toxicity
timeFrame: every two weeks up to 26 weeks during treatment
measure: overall survival
timeFrame: From date of trial enrolment until the date of death from any cause, assessed every two weeks up to 26 weeks during treatment; every 2-3 months afterwards up to 60 months
measure: Progression-free survival
timeFrame: From date of trial enrolment until the date of documented progression or date of death from any cause, whichever came first, assessed every two months up to 6 months during treatment; every 2-3 months afterwards up to 60 months
Other outcomes:
Locations:
city: Milan
country: Italy
facility: IRCCS S Raffaele
Study officials:
affiliation: IRCCS S RAFFAELE
name: Michele Reni, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Reni M, Zanon S, Peretti U, Chiaravalli M, Barone D, Pircher C, Balzano G, Macchini M, Romi S, Gritti E, Mazza E, Nicoletti R, Doglioni C, Falconi M, Gianni L. Nab-paclitaxel plus gemcitabine with or without capecitabine and cisplatin in metastatic pancreatic adenocarcinoma (PACT-19): a randomised phase 2 trial. Lancet Gastroenterol Hepatol. 2018 Oct;3(10):691-697. doi: 10.1016/S2468-1253(18)30196-1. Epub 2018 Jul 7.
citation: Reni M, Zanon S, Balzano G, Passoni P, Pircher C, Chiaravalli M, Fugazza C, Ceraulo D, Nicoletti R, Arcidiacono PG, Macchini M, Peretti U, Castoldi R, Doglioni C, Falconi M, Partelli S, Gianni L. A randomised phase 2 trial of nab-paclitaxel plus gemcitabine with or without capecitabine and cisplatin in locally advanced or borderline resectable pancreatic adenocarcinoma. Eur J Cancer. 2018 Oct;102:95-102. doi: 10.1016/j.ejca.2018.07.007. Epub 2018 Aug 24.
citation: Reni M, Balzano G, Zanon S, Passoni P, Nicoletti R, Arcidiacono PG, Pepe G, Doglioni C, Fugazza C, Ceraulo D, Falconi M, Gianni L. Phase 1B trial of Nab-paclitaxel plus gemcitabine, capecitabine, and cisplatin (PAXG regimen) in patients with unresectable or borderline resectable pancreatic adenocarcinoma. Br J Cancer. 2016 Jul 26;115(3):290-6. doi: 10.1038/bjc.2016.209. Epub 2016 Jul 12.