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

August 31, 2017 updated by: Michele Reni, IRCCS San Raffaele

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

137

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Milan, Italy, 20132
        • IRCCS S Raffaele

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: PAXG regimen
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
Drug: cisplatin
cisplatin at 30 mg/m2 on days 1 and 15
Other Names:
  • cisplatino TEVA
Drug: capecitabine
capecitabine at 1250 mg/ m2 days 1-28
Other Names:
  • XELODA
Drug: gemcitabine
gemcitabine at 800 mg/ m2 on days 1 and 15 in arm A; at 1000 mg/m2 on days 1, 8 and 15 in arm B
Other Names:
  • Gemzar
Drug: nab-paclitaxel
nab-paclitaxel at the recommended phase II dose day 1 and 15 in arm A; at 125 mg/m2 on days 1, 8 and 15 in arm B
Other Names:
  • abraxane
ACTIVE_COMPARATOR: gemcitabine + nab-paclitaxel
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
Drug: gemcitabine
gemcitabine at 800 mg/ m2 on days 1 and 15 in arm A; at 1000 mg/m2 on days 1, 8 and 15 in arm B
Other Names:
  • Gemzar
Drug: nab-paclitaxel
nab-paclitaxel at the recommended phase II dose day 1 and 15 in arm A; at 125 mg/m2 on days 1, 8 and 15 in arm B
Other Names:
  • abraxane

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
first cycle toxicity for phase I part
Time Frame: after one month from treatment start

Dose Limiting Toxicity definition: DLT will be defined as any of the following events attributable to the administered study drugs:

  • Hematologic toxicity

    • Grade ≥ 4 neutropenia lasting 7 days or more
    • Grade ≥ 3 febrile neutropenia or fever of unknown origin ≥ 38.5°C
    • Grade 4 thrombocytopenia
    • Grade 3 thrombocytopenia which required transfusions
  • Nausea or vomiting Grade ≥ 3 nausea or vomiting despite maximal antiemetic therapy
  • Diarrhea Grade ≥ 3 diarrhea despite optimal management of the event
  • Neurological toxicity Any Grade ≥ 2 neurological toxicity
  • Other non-hematologic toxicity Any grade ≥ 3 toxicities or representing a shift by 2 grades from baseline (in case of abnormal baseline)
  • Failure to recover Failure to recover to grade ≤ 1 toxicity (except alopecia) or to baseline values after delaying the initiation of next cycle by > 2 weeks.
after one month from treatment start
progression-free survival for phase II part, stage IV patients
Time Frame: after 6 months from randomization
rate of progression-free patients at 6 months from randomization
after 6 months from randomization
resectability rate for phase II part, stage III patients
Time Frame: after 4 and 6 months from treatment start
rate of resectable patients at at time of CT evaluation and multidisciplinary assessment after 4 and 6 months from treatment start
after 4 and 6 months from treatment start

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
response rate
Time Frame: 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
contrast enhanced CT scan tumor assessment
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
biochemical response rate
Time Frame: 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
blood sample for CA19.9 assessment
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
toxicity
Time Frame: every two weeks up to 26 weeks during treatment
outpatients visits; laboratory
every two weeks up to 26 weeks during treatment
overall survival
Time Frame: 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
outpatients visit; phone interviews
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
Progression-free survival
Time Frame: 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
contrast enhanced CT scan
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

IRCCS San Raffaele

Investigators

  • Principal Investigator: Michele Reni, MD, IRCCS S Raffaele

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2012

Primary Completion (ACTUAL)

February 1, 2017

Study Completion (ACTUAL)

August 1, 2017

Study Registration Dates

First Submitted

November 4, 2012

First Submitted That Met QC Criteria

November 14, 2012

First Posted (ESTIMATE)

November 21, 2012

Study Record Updates

Last Update Posted (ACTUAL)

September 1, 2017

Last Update Submitted That Met QC Criteria

August 31, 2017

Last Verified

August 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PACT-19
  • 2012-001763-75 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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