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

Yonsei University

Status and phase

Unknown

Phase 2

Conditions

Metastatic Pancreatic Cancer

Treatments

Drug: Modified Gemcitabine plus nab-Paclitaxel Combination Chemotherapy

Study type

Interventional

Funder types

Other

Identifiers

NCT03502343

4-2017-0840

Details and patient eligibility

About

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.

Full 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.

Enrollment

52 estimated patients

Sex

All

Ages

19+ years old

Volunteers

No Healthy Volunteers

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