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

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2015 by IRCCS San Raffaele
Sponsor:
Information provided by (Responsible Party):
Michele Reni, IRCCS San Raffaele
ClinicalTrials.gov Identifier:
NCT01730222
First received: November 4, 2012
Last updated: April 23, 2015
Last verified: April 2015
  Purpose

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.


Condition Intervention Phase
Pancreatic Cancer
Drug: cisplatin
Drug: capecitabine
Drug: gemcitabine
Drug: nab-paclitaxel
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I-II Study of PAXG in Stage III-IV Pancreatic Adenocarcinoma

Resource links provided by NLM:


Further study details as provided by IRCCS San Raffaele:

Primary Outcome Measures:
  • first cycle toxicity for phase I part [ Time Frame: after one month from treatment start ] [ Designated as safety issue: Yes ]

    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.

  • progression-free survival for phase II part, stage IV patients [ Time Frame: after 6 months from randomization ] [ Designated as safety issue: No ]
    rate of progression-free patients at 6 months from randomization

  • resectability rate for phase II part, stage III patients [ Time Frame: after 4 and 6 months from treatment start ] [ Designated as safety issue: No ]
    rate of resectable patients at at time of CT evaluation and multidisciplinary assessment after 4 and 6 months from treatment start


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    contrast enhanced CT scan tumor assessment

  • 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 ] [ Designated as safety issue: No ]
    blood sample for CA19.9 assessment

  • toxicity [ Time Frame: every two weeks up to 26 weeks during treatment ] [ Designated as safety issue: Yes ]
    outpatients visits; laboratory

  • 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 ] [ Designated as safety issue: Yes ]
    outpatients visit; phone interviews

  • 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 ] [ Designated as safety issue: No ]
    contrast enhanced CT scan


Estimated Enrollment: 134
Study Start Date: November 2012
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: cisplatino TEVA
Drug: capecitabine
capecitabine at 1250 mg/ m2 days 1-28
Other Name: 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 Name: 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 Name: 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 Name: 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 Name: abraxane

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

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01730222

Locations
Italy
IRCCS S Raffaele Recruiting
Milan, Italy, 20132
Contact: Michele Reni, MD    +39 02 26437644    reni.michele@hsr.it   
Principal Investigator: Michele Reni, MD         
Sponsors and Collaborators
IRCCS San Raffaele
Investigators
Principal Investigator: Michele Reni, MD IRCCS S RAFFAELE
  More Information

No publications provided

Responsible Party: Michele Reni, Principal Investigator, IRCCS San Raffaele
ClinicalTrials.gov Identifier: NCT01730222     History of Changes
Other Study ID Numbers: PACT-19, 2012-001763-75
Study First Received: November 4, 2012
Last Updated: April 23, 2015
Health Authority: Italy: Ministry of Health

Keywords provided by IRCCS San Raffaele:
pancreatic adenocarcinoma
stage III disease
stage IV disease
chemotherapy

Additional relevant MeSH terms:
Adenocarcinoma
Pancreatic Neoplasms
Carcinoma
Digestive System Diseases
Digestive System Neoplasms
Endocrine Gland Neoplasms
Endocrine System Diseases
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Pancreatic Diseases
Capecitabine
Cisplatin
Gemcitabine
Paclitaxel
Anti-Infective Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Antiviral Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on April 23, 2015