A Phase I-II Study of PAXG in Stage III-IV Pancreatic Adenocarcinoma (PACT-19)
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| ClinicalTrials.gov Identifier: NCT01730222 |
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Recruitment Status :
Completed
First Posted : November 21, 2012
Last Update Posted : September 1, 2017
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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 or disease | Intervention/treatment | Phase |
|---|---|---|
| Pancreatic Cancer | Drug: cisplatin Drug: capecitabine Drug: gemcitabine Drug: nab-paclitaxel | Phase 1 Phase 2 |
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 (Clinical Trial) |
| Actual Enrollment : | 137 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase I-II Study of PAXG in Stage III-IV Pancreatic Adenocarcinoma |
| Study Start Date : | November 2012 |
| Actual Primary Completion Date : | February 2017 |
| Actual Study Completion Date : | August 2017 |
| Arm | Intervention/treatment |
|---|---|
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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
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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 |
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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
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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 |
- 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:
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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.
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- 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
- 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
- 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
- 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
- toxicity [ Time Frame: every two weeks up to 26 weeks during treatment ]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 ]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 ]contrast enhanced CT scan
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| Ages Eligible for Study: | 18 Years to 75 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01730222
| Italy | |
| IRCCS S Raffaele | |
| Milan, Italy, 20132 | |
| Principal Investigator: | Michele Reni, MD | IRCCS S RAFFAELE |
| Responsible Party: | Michele Reni, Principal Investigator, IRCCS San Raffaele |
| ClinicalTrials.gov Identifier: | NCT01730222 |
| Other Study ID Numbers: |
PACT-19 2012-001763-75 ( EudraCT Number ) |
| First Posted: | November 21, 2012 Key Record Dates |
| Last Update Posted: | September 1, 2017 |
| Last Verified: | August 2017 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
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pancreatic adenocarcinoma stage III disease stage IV disease chemotherapy |
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Adenocarcinoma Carcinoma Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Gemcitabine Paclitaxel Capecitabine Antineoplastic Agents, Phytogenic Antineoplastic Agents Tubulin Modulators |
Antimitotic Agents Mitosis Modulators Molecular Mechanisms of Pharmacological Action Antimetabolites, Antineoplastic Antimetabolites Antiviral Agents Anti-Infective Agents Enzyme Inhibitors Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs |