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

Pancreatic Cancer Clinical Trial

— PACT-19  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01730222
• Other study ID #: PACT-19
• Secondary ID: 2012-001763-75
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: November 4, 2012
• Last updated: August 31, 2017
• Start date: November 2012
• Est. completion date: August 2017

Study information

• Verified date: August 2017
• Source: IRCCS San Raffaele
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 137
• Est. completion date: August 2017
• Est. primary completion date: February 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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).

Related Conditions & MeSH terms

• Adenocarcinoma
• Pancreatic Cancer
• Pancreatic Neoplasms

Intervention

Drug:
• cisplatin
cisplatin at 30 mg/m2 on days 1 and 15
• capecitabine
capecitabine at 1250 mg/ m2 days 1-28
• 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
• 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

Locations

Country	Name	City	State
Italy	IRCCS S Raffaele	Milan

Sponsors (1)

Lead Sponsor	Collaborator
IRCCS San Raffaele

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	after one month from treatment start
Primary	progression-free survival for phase II part, stage IV patients	rate of progression-free patients at 6 months from randomization	after 6 months from randomization
Primary	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	after 4 and 6 months from treatment start
Secondary	response rate	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
Secondary	biochemical response rate	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
Secondary	toxicity	outpatients visits; laboratory	every two weeks up to 26 weeks during treatment
Secondary	overall survival	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
Secondary	Progression-free survival	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