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Efficacy and Safety of Modified Nab-Paclitaxel Plus Gemcitabine Chemotherapy for Metastatic Pancreatic Cancer

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ClinicalTrials.gov Identifier: NCT03502343
Recruitment Status : Recruiting
First Posted : April 18, 2018
Last Update Posted : April 18, 2018
Sponsor:
Information provided by (Responsible Party):
Yonsei University

Brief Summary:

Recently, a retrospective study reported the efficacy and safety of modified gemcitabine plus nab-paclitaxel (GnP), which were administered biweekly (on days 1 and 15). With 79 patients of metastatic pancreatic cancer, this study reported similar efficacy and improved toxicity profile compared with standard dose GnP (OS 10 months, PFS 5.4 months, Grade ≥3 Neutropenia 19%, Grade ≥3 sensory neuropathy 1.6%). Also, several studies reported that dose reduction of nab-paclitaxel in breast or pancreatic cancer treatment was not related of decreased survival, or related with prolonged survival and increased treatment exposure. However, this finding need to be evaluated in prospective clinical trial.

This phase II trial will evaluate the efficacy and safety of modified GnP, which omit the day 8 administration of nab-paclitaxel, in metastatic pancreatic cancer.


Condition or disease Intervention/treatment Phase
Metastatic Pancreatic Cancer Drug: Modified Gemcitabine plus nab-Paclitaxel Combination Chemotherapy Phase 2

Detailed Description:

Gemcitabine-based combination therapy have been used to prolong survival for patient with pancreatic cancer. In early 2010s, gemcitabine plus nab-paclitaxel (GnP) combination regimen have been introduced based on the results of randomized phase III clinical trial that showed survival benefit than gemcitabine monotherapy. Nab-paclitaxel is a nanoparticle albumin-bound paclitaxel that showed anti-tumor activity as well as synergistic effect in combination with gemcitabine.

In the Metastatic Pancreatic Adenocarcinoma Clinical Trial (MPACT), the maximal tolerated nab-paclitaxel dose (125 mg/m2) was administrated with 1000 mg/m2 of gemcitabine, on days 1, 8 and 15 for 4 weeks cycle. This combination therapy showed favorable treatment response, but notable severe adverse events were also reported. Grade 3 or higher neuropathy and neutropenia occurred in 17% and 38% of patients, respectively. Also, dose reduction was required in approximately half of the patients.

Recently, a retrospective study reported the efficacy and safety of modified GnP, which were administered biweekly (on days 1 and 15). With 79 patients of metastatic pancreatic cancer, this study reported similar efficacy and improved toxicity profile compared with standard dose GnP (OS 10 months, PFS 5.4 months, Grade ≥3 Neutropenia 19%, Grade ≥3 sensory neuropathy 1.6%). Also, several studies reported that dose reduction of nab-paclitaxel in breast or pancreatic cancer treatment was not related of decreased survival, or related with prolonged survival and increased treatment exposure. However, this finding need to be evaluated in prospective clinical trial.

This phase II trial will evaluate the efficacy and safety of modified GnP, which omit the day 8 administration of nab-paclitaxel, in metastatic pancreatic cancer.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 52 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Efficacy and Safety of Modified Nab-Paclitaxel Plus Gemcitabine Chemotherapy for Metastatic Pancreatic Cancer: A Single-arm Phase II Clinical Trial
Actual Study Start Date : April 1, 2018
Estimated Primary Completion Date : April 2020
Estimated Study Completion Date : June 2020


Arm Intervention/treatment
Experimental: Modified Gemcitabine plus nab-Paclitaxel
The intervention group
Drug: Modified Gemcitabine plus nab-Paclitaxel Combination Chemotherapy

All patients will receive slow (over 30-40 minutes) intravenous administration of nab-paclitaxel (125 mg/m2) on days 1 and 15, and gemcitabine (1000 mg/m2) on days 1, 8, and 15 of a 28- day cycle (every 4 weeks). Treatment will discontinue if disease progression or intolerable toxicity is observed, if the patient withdraws from the study, or at the physician's discretion.

Dose reduction of the chemotherapeutic agent and/or delay of administration is allowed if serious treatment-related AEs occur, according to specified guideline in study protocol (Level 1: 100% -> 80%; Level 2: 80% -> 60%). If dose reduction is needed more than Level 2, the patient will be dropped from the trial.





Primary Outcome Measures :
  1. Objective response rate [ Time Frame: Every 8 weeks until dropout up to 104 weeks ]
    To evaluate treatment efficacy, computed tomography scan, magnetic resonance imaging, or 18F-fluorodeoxyglucose-positron emission tomography (18F-FDGPET) scan will be performed every 8 weeks. Treatment responses according to the RECIST criteria will be reported by designated radiologists and final disease assessment will be independently made by the attending physician. The proportion of patients with the best response of complete response (CR), partial response (PR) is defined as objective response rate.

  2. Disease control rate [ Time Frame: Every 8 weeks until dropout up to 104 weeks ]
    To evaluate treatment efficacy, computed tomography scan, magnetic resonance imaging, or 18F-fluorodeoxyglucose-positron emission tomography (18F-FDGPET) scan will be performed every 8 weeks. Disease control rate is defined as the proportion of patients with the best response of CR, PR and stable disease.


Secondary Outcome Measures :
  1. Overall survival [ Time Frame: Every 8 weeks from date of drug administration until the date of patient`s death, loss of follow-up, or end of the trial up to 104 weeks ]
    The overall survival is defined as from the date of enrollment to the date of the last follow-up or death of all causes. In case of loss of follow-up, the censoring date will be the day on which the survival is confirmed before follow-up loss.

  2. Progression-free survival [ Time Frame: Every 8 weeks from date of drug administration until the date of patient`s death, loss of follow-up, or end of the trial up to 104 weeks ]

    The progression free survival is defined as from the date of treatment initiation to the date of the event. The event is defined as the date of disease progression or patient`s death, which occured first.

    In case of loss of follow-up, the censoring date will be the day on which the survival is confirmed before follow-up loss.


  3. Adverse event [ Time Frame: Until dropout from the trial up to 104 weeks ]
    Adverse events will be assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.03) before each cycle until study dropout.



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Ages Eligible for Study:   19 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Pathologically or cytologically confirmed pancreatic adenocarcinoma
  • Coexisting extrapancreatic distant metastasis
  • Older than 19 years old
  • Measurable primary tumor in pancreas on imaging study at the time of diagnosis, according to the RECIST criteria

Exclusion Criteria:

  • Previous history of palliative systemic chemotherapy due to pancreatic cancer
  • Existence of active malignancy of other organ which diagnosed in last five years (except the squamous cell carcinoma or basal cell tumor of skin)
  • Existence of life-threatening co-morbidity
  • Poor performance state (ECOG ≥2)
  • Suspected severe bone marrow suppression (Neutrophil count< 1,500/mm3, Hemoglobin< 9 g/dL, Platelet count< 75,000/mm3)
  • Suspected severe liver dysfunction (Total bilirubin or Prothrombin Time > 1.5 times of upper normal range) or renal dysfunction (estimated GFR < 50/ml/min/1.73 m²)
  • Pre-existence of ≥grade 2 peripheral sensory neuropathy
  • Existence of brain metastasis or meningeal carcinomatosis
  • Patient with pregnancy or ongoing breast feeding
  • Do not agree with the informed consent

Information from the National Library of Medicine

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): NCT03502343


Locations
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Korea, Republic of
Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine Recruiting
Seoul, Korea, Republic of, 03722
Contact: Seungmin Bang, MD, Ph.D    02-2228-1995    Bang7028@yuhs.ac   
Sponsors and Collaborators
Yonsei University

Publications:
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Responsible Party: Yonsei University
ClinicalTrials.gov Identifier: NCT03502343     History of Changes
Other Study ID Numbers: 4-2017-0840
First Posted: April 18, 2018    Key Record Dates
Last Update Posted: April 18, 2018
Last Verified: April 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Yonsei University:
Pancreatic cancer
Metastatic
Modified
Gemcitabine
nab-Paclitaxel
Additional relevant MeSH terms:
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Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Pancreatic Diseases
Digestive System Diseases
Endocrine System Diseases
Gemcitabine
Paclitaxel
Albumin-Bound Paclitaxel
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