Back to results

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

Primary Purpose

Pancreatic Cancer

Status

Completed

Phase

Phase 1

Locations

Italy

Study Type

Interventional

Intervention

cisplatin

capecitabine

gemcitabine

nab-paclitaxel

About this trial

This is an interventional treatment trial for Pancreatic Cancer focused on measuring pancreatic adenocarcinoma, stage III disease, stage IV disease, chemotherapy

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept 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).

Sites / Locations

IRCCS S Raffaele

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

PAXG regimen

gemcitabine + nab-paclitaxel

Arm 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

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

Outcomes

Primary Outcome Measures

first cycle toxicity for phase I part

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

rate of progression-free patients at 6 months from randomization

resectability rate for phase II part, stage III patients

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

contrast enhanced CT scan tumor assessment

biochemical response rate

blood sample for CA19.9 assessment

toxicity

outpatients visits; laboratory

overall survival

outpatients visit; phone interviews

Progression-free survival

contrast enhanced CT scan

Full Information

NCT ID

NCT01730222

First Posted

November 4, 2012

Last Updated

August 31, 2017

Sponsor

IRCCS San Raffaele

1. Study Identification

Unique Protocol Identification Number

NCT01730222

Brief Title

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

Acronym

PACT-19

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

August 2017

Overall Recruitment Status

Completed

Study Start Date

November 2012 (undefined)

Primary Completion Date

February 2017 (Actual)

Study Completion Date

August 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

IRCCS San Raffaele

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Pancreatic Cancer

Keywords

pancreatic adenocarcinoma, stage III disease, stage IV disease, chemotherapy

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

137 (Actual)

8. Arms, Groups, and Interventions

Arm Title

PAXG regimen

Arm Type

Experimental

Arm 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

Arm Title

gemcitabine + nab-paclitaxel

Arm Type

Active Comparator

Arm 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

Intervention Type

Drug

Intervention Name(s)

cisplatin

Other Intervention Name(s)

cisplatino TEVA

Intervention Description

cisplatin at 30 mg/m2 on days 1 and 15

Intervention Type

Drug

Intervention Name(s)

capecitabine

Other Intervention Name(s)

XELODA

Intervention Description

capecitabine at 1250 mg/ m2 days 1-28

Intervention Type

Drug

Intervention Name(s)

gemcitabine

Other Intervention Name(s)

Gemzar

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

nab-paclitaxel

Other Intervention Name(s)

abraxane

Intervention Description

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

Primary Outcome Measure Information:

Title

first cycle toxicity for phase I part

Description

Time Frame

after one month from treatment start

Title

progression-free survival for phase II part, stage IV patients

Description

rate of progression-free patients at 6 months from randomization

Time Frame

after 6 months from randomization

Title

resectability rate for phase II part, stage III patients

Description

rate of resectable patients at at time of CT evaluation and multidisciplinary assessment after 4 and 6 months from treatment start

Time Frame

after 4 and 6 months from treatment start

Secondary Outcome Measure Information:

Title

response rate

Description

contrast enhanced CT scan tumor assessment

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

Title

biochemical response rate

Description

blood sample for CA19.9 assessment

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

Title

toxicity

Description

outpatients visits; laboratory

Time Frame

every two weeks up to 26 weeks during treatment

Title

overall survival

Description

outpatients visit; phone interviews

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

Title

Progression-free survival

Description

contrast enhanced CT scan

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

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).

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Michele Reni, MD

Organizational Affiliation

IRCCS S RAFFAELE

Official's Role

Principal Investigator

Facility Information:

Facility Name

IRCCS S Raffaele

City

Milan

ZIP/Postal Code

20132

Country

Italy

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

30220407

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.

Results Reference

derived

PubMed Identifier

30149366

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.

Results Reference

derived

PubMed Identifier

27404453

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.

Results Reference

derived

Learn more about this trial

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

We'll reach out to this number within 24 hrs