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

NCT03502343 | Unknown Phase 2

• 1 other identifier: 4-2017-0840
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

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.

Conditions

Metastatic Pancreatic Cancer

Keywords

Pancreatic cancer; Metastatic; Modified; Gemcitabine; nab-Paclitaxel

Outcome Measures

Primary Outcomes (2)

• Objective response rate

  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.

  Every 8 weeks until dropout up to 104 weeks

• Disease control rate

  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.

  Every 8 weeks until dropout up to 104 weeks

Secondary Outcomes (3)

• 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

• 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

• Adverse event

  Until dropout from the trial up to 104 weeks

Study Arms (1)

Modified Gemcitabine plus nab-Paclitaxel

EXPERIMENTAL

The intervention group

Drug: Modified Gemcitabine plus nab-Paclitaxel Combination Chemotherapy

Interventions

Modified Gemcitabine plus nab-Paclitaxel Combination Chemotherapy DRUG

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.

Modified Gemcitabine plus nab-Paclitaxel

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Yonsei University: lead

Study Sites (1)

Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine

Seoul, 03722, South Korea

RECRUITING

Related Publications (4)

• 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.

  PMID: 24131140 BACKGROUND

• 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.

  PMID: 28203300 BACKGROUND

• 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.

  PMID: 22728026 BACKGROUND

• 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.

  PMID: 27284481 BACKGROUND

MeSH Terms

Conditions

Pancreatic Neoplasms; Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 3, 2018
• First Posted: April 18, 2018
• Study Start: April 1, 2018
• Primary Completion: April 1, 2020
• Study Completion: June 1, 2020
• Last Updated: April 18, 2018

Record last verified: 2018-04

Locations

KR (1)