Neoadjuvant Plus Adjuvant or Only Adjuvant Nab- Paclitaxel Plus Gemcitabine for Resectable Pancreatic Cancer

Phase 2

Completed

• Conditions: Ductal Adenocarcinoma of the Pancreas; Resectable Pancreatic Cancer
• Interventions: Drug: adjuvant nab-paclitaxel/gemcitabine; Drug: perioperative nab-paclitaxel/gemcitabine

• Registration Number: NCT02047513
• Lead Sponsor: AIO-Studien-gGmbH

Brief Summary

NEONAX is an interventional, prospective, randomized, controlled, open label, two sided survival phase II studies against a fixed survival probability, with an unconnected analysis of the results in both experimental arms.

Determining the impact of 2 cycles of Perioperative nab-paclitaxel/gemcitabine followed by surgery and 4 cycles of adjuvant nab-paclitaxel/gemcitabine or 6 cycles of adjuvant nab-paclitaxel/gemcitabine on the Disease free survival (DFS) rate at 18 months post randomization

Detailed Description

The planned trial will enable us to address the following issues:

* Identification of patients who benefit from surgery. Tumor progress during intensified Perioperative chemotherapy is likely to indicate a particularly poor prognosis suggesting that these patients would not have benefitted from immediate surgery.

* Assess tumor response/downsizing using nab-paclitaxel/gemcitabine also at the molecular level

* Can we achieve a better systemic tumor control or reduce the metastatic spread using nab-paclitaxel/gemcitabine compared to adjuvant gemcitabine

* Examining the effect of a more efficacious chemotherapy regimen (nab-paclitaxel/gemcitabine) in the adjuvant setting

* Defining the impact of a perioperative or adjuvant chemotherapy with gemcitabine/nab-paclitaxel on DFS and 3-year Overall survival (OS)

Histopathological tumor regression will be evaluated in addition to tumor size measurement according to Response Evaluation Criteria In Solid Tumors (RECIST). We will establish a histopathological tumor regression score to evaluate the efficacy of the neoadjuvant treatment. For this score we will examine tumor core biopsies obtained prior to neoadjuvant treatment and histological tumor specimen after surgery in both arms.

To reliably determine R0 resections, the resected specimen will be prepared for pathology in a defined manner according to the procedure set out in the German S3 guidelines for pancreatic cancer.

This trial provides the unique opportunity in pancreatic cancer to obtain material prior to and after surgery for biomarker analysis and correlation with outcome. We will perform pharmacogenomic candidate gene analysis of hENT1 (human equilibrative nucleoside transporter-1), CDA (cell differentiation agent), DCK (Desoxycytidin-Kinase) and 5´nucleotidase in both arms.

Study Timeline

• Study First Submitted: 2014-01-09
• Study First Submitted QC: 2014-01-27
• Study First Posted: 2014-01-28
• Study Start: 2015-07
• Primary Completion: 2021-04
• Study Completion: 2022-10
• Status Verified: 2023-06
• Last Update Submitted: 2023-06-13
• Last Update Posted: 2023-06-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 127

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
adjuvant nab-paclitaxel/gemcitabine	adjuvant nab-paclitaxel/gemcitabine	Surgery followed by adjuvant chemotherapy (24 weeks, begin within 12 weeks after surgery), follow-up per patient: Until end of study or death
perioperative nab-paclitaxel/gemcitabine	perioperative nab-paclitaxel/gemcitabine	neoadjuvant chemotherapy (8 weeks) preceding surgery (3 weeks after completion of chemotherapy) followed by adjuvant chemotherapy (16 weeks, begin within 12 weeks after surgery)

Primary Outcome Measures

Name	Time	Method
Time to Disease free survival (DFS)	18 months after randomization	To improve the DFS rate at 18 months in at least one arm to≥ 55%

Secondary Outcome Measures

Name	Time	Method
toxicity	57 months	• Dropout rate due to toxicity in the neoadjuvant study
Tumor response	66 months	To assess tumor response using the imaging data (CT scans, MRI-scans) obtained during the trial
morbidity and mortality	7 years	• pre- and postoperative morbidity and mortality in both studies
Disease progression	7 years	• Disease progression during neoadjuvant therapy
Safety	57 months	• Assessment of safety
Overall survival	7 years	• Overall survival in both studies
tumor recurrence	7 years	• First site of tumor recurrence in both studies
quality of life	57 months	• Explorative analysis of health related quality of life in both studies
pharmacogenomic markers, tumor-biomarkers and molecular analyses	57 months	• Correlation of DFS, OS and tumor regression with pharmacogenomic markers, tumor-biomarkers and molecular analyses in both studies
Tumor recurrence	66 months	To assess tumor recurrence using the imaging data (CT scans, MRI-scans) obtained during the trial
resection rate	53 months	• R0 and R1 resection rate in both groups as assessed according to the German S3 guidelines
Correlation of tumor regression and R0 resection	57 months	• Correlation of tumor regression and R0 resection rate with response according to RECIST v1.1 in the perioperative study

Trial Locations

Locations (1)

University of Ulm, Dept. of Internal Medicine I; 🇩🇪 Ulm, Germany