Clinical trial NCT03502343: Efficacy and Safety of Modified Nab-Paclitaxel Plus Gemcitabine Chemotherapy for Metastatic Pancreatic Cancer
Official title: Efficacy and Safety of Modified Nab-Paclitaxel Plus Gemcitabine Chemotherapy for Metastatic Pancreatic Cancer: A Single-arm Phase II Clinical Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Metastatic Pancreatic Cancer
Keywords: Pancreatic cancer
Metastatic
Modified
Gemcitabine
nab-Paclitaxel
Lead sponsor: Yonsei University
Sponsor class: OTHER
First posted: 2018-04-18
Enrollment: 52
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Objective response rate
timeFrame: Every 8 weeks until dropout up to 104 weeks
measure: Disease control rate
timeFrame: Every 8 weeks until dropout up to 104 weeks
Secondary outcomes:
measure: Overall survival
timeFrame: 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
measure: Progression-free survival
timeFrame: 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
measure: Adverse event
timeFrame: Until dropout from the trial up to 104 weeks
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine
Study officials:
References:
citation: Von Hoff DD, Ervin T, Arena FP, Chiorean EG, Infante J, Moore M, Seay T, Tjulandin SA, Ma WW, Saleh MN, Harris M, Reni M, Dowden S, Laheru D, Bahary N, Ramanathan RK, Tabernero J, Hidalgo M, Goldstein D, Van Cutsem E, Wei X, Iglesias J, Renschler MF. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013 Oct 31;369(18):1691-703. doi: 10.1056/NEJMoa1304369. Epub 2013 Oct 16.
citation: Ahn DH, Krishna K, Blazer M, Reardon J, Wei L, Wu C, Ciombor KK, Noonan AM, Mikhail S, Bekaii-Saab T. A modified regimen of biweekly gemcitabine and nab-paclitaxel in patients with metastatic pancreatic cancer is both tolerable and effective: a retrospective analysis. Ther Adv Med Oncol. 2017 Feb;9(2):75-82. doi: 10.1177/1758834016676011. Epub 2016 Nov 2.
citation: Gradishar WJ, Krasnojon D, Cheporov S, Makhson AN, Manikhas GM, Clawson A, Bhar P, McGuire JR, Iglesias J. Phase II trial of nab-paclitaxel compared with docetaxel as first-line chemotherapy in patients with metastatic breast cancer: final analysis of overall survival. Clin Breast Cancer. 2012 Oct;12(5):313-21. doi: 10.1016/j.clbc.2012.05.001. Epub 2012 Jun 23.
citation: Scheithauer W, Ramanathan RK, Moore M, Macarulla T, Goldstein D, Hammel P, Kunzmann V, Liu H, McGovern D, Romano A, Von Hoff DD. Dose modification and efficacy of nab-paclitaxel plus gemcitabine vs. gemcitabine for patients with metastatic pancreatic cancer: phase III MPACT trial. J Gastrointest Oncol. 2016 Jun;7(3):469-78. doi: 10.21037/jgo.2016.01.03.