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

Phase 2

• Conditions: Metastatic Pancreatic Cancer
• Interventions: Drug: Modified Gemcitabine plus nab-Paclitaxel Combination Chemotherapy

• Registration Number: NCT03502343
• Lead Sponsor: 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.

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.

Study Timeline

• Status Verified: 2018-04
• Study Start: 2018-04-01
• Study First Submitted: 2018-04-03
• Study First Submitted QC: 2018-04-10
• Last Update Submitted: 2018-04-10
• Study First Posted: 2018-04-18
• Last Update Posted: 2018-04-18
• Primary Completion: 2020-04
• Study Completion: 2020-06

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 52

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Modified Gemcitabine plus nab-Paclitaxel	Modified Gemcitabine plus nab-Paclitaxel Combination Chemotherapy	The intervention group

Primary Outcome Measures

Name	Time	Method
Objective response rate	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.
Disease control rate	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

Name	Time	Method
Overall survival	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.
Progression-free survival	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.
Adverse event	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.

Trial Locations

Locations (1)

Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine; 🇰🇷 Seoul, Korea, Republic of