Skip to main content
OpenTrials
Completed

NCT Number: NCT01730222

A Phase I-II Study of PAXG in Stage III-IV Pancreatic Adenocarcinoma

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.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Pancreatic Cancer Digestive System Diseases Digestive System Neoplasms Disease Endocrine Gland Neoplasms Endocrine System Diseases Neoplasms Neoplasms by Site Pancreatic Diseases Pancreatic Neoplasms Pathologic Processes Pathological Conditions, Signs and Symptoms

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

IRCCS S Raffaele

Milan, 20132, Italy

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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).

Treatment and study plan

Cisplatin

Drug

cisplatin at 30 mg/m2 on days 1 and 15

Other names: cisplatino TEVA

Capecitabine

Drug

capecitabine at 1250 mg/ m2 days 1-28

Other names: XELODA

Gemcitabine

Drug

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

Nab-paclitaxel

Drug

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

Primary outcomes

  1. 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.

  2. 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

  3. 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

Secondary outcomes

  1. 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

  2. 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

  3. toxicity

    Time frame: every two weeks up to 26 weeks during treatment

    outpatients visits; laboratory

  4. 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

  5. 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

Sponsors and collaborators

Lead sponsor

IRCCS San Raffaele

Other

Registry information

Acronym: PACT-19

Important dates

Study start
2012
Primary completion
2017
Study completion
2017
First posted
Nov 21, 2012
Registry last updated
Sep 1, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.