Neoadjuvant Treatment in Resectable Pancreatic Cancer (NEOPA)

May 4, 2018 updated by: Universitätsklinikum Hamburg-Eppendorf

Sequential Neoadjuvant Chemoradiotherapy (CRT) Followed by Curative Surgery vs. Primary Surgery Alone for Resectable, Non-metastasized Pancreatic Adenocarcinoma

Sequential Neoadjuvant Chemoradiotherapy (CRT) Followed by Curative Surgery vs. Primary Surgery Alone for Resectable, Non-metastasized Pancreatic Adenocarcinoma

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Median overall-survival (OS) after surgery in curative intent for non-metastasized pancreas cancer ranges under study conditions from 17.9 months to 23.6 months. Tumor recurrence occurs locally, at distant sites (liver, peritoneum, lungs), or both. Observational and autopsy series report local recurrence rates of up to 87% even after potentially "curative" R0 resection. To achieve better local control, neoadjuvant chemo-radiation therapy (CRT) has been suggested for preoperative tumour downsizing, to elevate the likelihood of curative, margin-negative R0 resection and to increase the OS rate. However, controlled, randomized trials addressing the impact of neoadjuvant CRT survival do not exist. The underlying hypothesis of this randomized, two-armed, open-label, multicenter, phase III trial is that neoadjuvant CRT increases the three-year overall survival by 12% (30% to 42%) compared to patients undergoing upfront surgery for resectable pancreatic cancer. Overall, 410 patients (n=205 in each study arm) will be enrolled in the trial, taking into regard an expected drop out rate of 7% and allocated either to receive neoadjuvant CRT prior to surgery or to undergo surgery alone. Circumferential resection margin status, i.e. R0 and R1 rates, respectively, surgical resectability rate, local and distant disease-free and global survival, and first site of tumor recurrence constitute further essential endpoints of the trial.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
32

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Hamburg, Germany, 20246
        • University Medical Center Hamburg-Eppendorf
      • Karlsruhe, Germany, 76133
        • Klinikum Karlsruhe
    • Baden-Württemberg
      • Freiburg, Baden-Württemberg, Germany, 79106
        • University Freiburg
      • Heidelberg, Baden-Württemberg, Germany, 69120
        • Heidelberg University
    • Bayer
      • Augsburg, Bayer, Germany, 86156
        • Klinikum Augsburg
    • Bayern
      • München, Bayern, Germany, 81675
        • Technische Universität München
      • Regensburg, Bayern, Germany, 93053
        • University Regensburg
    • Hessen
      • Darmstadt, Hessen, Germany, 64283
        • Klinikum Darmstadt
    • Mecklenburg-Vorpommern
      • Rostock, Mecklenburg-Vorpommern, Germany, 18057
        • University of Rostock
    • Niedersachsen
      • Hannover, Niedersachsen, Germany, 30625
        • Hannover Medical School
    • Nordrhein-Westfalen
      • Bochum, Nordrhein-Westfalen, Germany, 44791
        • St. Joseph Hospital Bochum
    • Saarland
      • Homburg, Saarland, Germany, 66421
        • Saarland University
    • Schleswig-Holstein
      • Kiel, Schleswig-Holstein, Germany, 24105
        • University of Schleswig-Holstein Kiel
      • Lübeck, Schleswig-Holstein, Germany, 23538
        • University of Schleswig-Holstein Lübeck
    • Thüringen
      • Gera, Thüringen, Germany, 07548
        • Klinikum Gera
      • Jena, Thüringen, Germany, 07747
        • University of Jena

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Histology-proven adenocarcinoma of the pancreatic head/uncinate process with a tumor size greater 2 cm (≥cT2) and/or close contact to the superior mesenteric vessels (≤3 mm in preoperative staging).
  • No evidence of metastasis to distant organs (liver, peritoneum, lung, others).
  • For determination of resectability, a multi-detector CT (MDCT) with at least 16 rows applying both oral and intravenous contrast media is performed. MDCT-based imaging focuses on the upper abdomen with native, arterial, and parenchyma phase, where the parenchyma phase should include the pelvis. Imaging criteria derived from the recent consensus definition of the Society of Surgical Oncology, the American Society of Clinical Oncology and the American Hepato-Pancreatico-Biliary Association [1] are applied for preoperative assessment of local resectability.
  • Potential Resectability: visualizable fat plane around celiac and superior mesenteric arteries, and patent superior mesenteric/portal vein (SMV/PV).
  • Borderline Resectability: substantial superior mesenteric/portal vein impingement, tumor abutment on the SMA < 180°, GDA encasement up to the origin of the hepatic artery, or colonic/mesenteric root invasion.
  • Karnofsky performance status ≥ 80%
  • Serum creatinine level ≤ 3.0 mg/dl
  • Serum total bilirubin level ≤ 3.0 mg/dl in the absence of biliary obstruction (In the event of biliary obstruction, patients allocated to the CRT group must undergo interventional endoscopy or percutaneous drainage for biliary decompression. Post-interventionally, bilirubin levels should be ≤ 3.0 mg/dl before patients are subjected to CRT. In control patients undergoing upfront surgery, serum total bilirubin levels ≤ 10.0 mg/dl are tolerated, unless clinical and laboratory signs of severe cholangitis take place. Patients with serum total bilirubin level > 10.0 mg/dl undergo preoperative biliary decompression, preferentially by interventional endoscopy)
  • White blood cell count ≥ 3.5 x 109/ml, platelet count ≥ 100 x 109/ml
  • Ability to understand and willingness to consent to formal requirements for study participation
  • Written informed consent

Exclusion Criteria:

  • Age ≤ 18 years
  • Neuroendocrine, acinar cancer
  • Cancers of the pancreatic body or tail, i.e. lesions left to the SMV
  • Recurrent disease
  • Infiltration of extrapancreatic organs (except duodenum and transverse colon)
  • Persistent cholestasis/cholangitis despite adequate biliary stenting
  • Gastric outlet obstruction, especially in the event of endoscopically evidenced tumor invasion into the gastroduodenal mucosa.
  • Tumor specific pre-treatment
  • History of gastrointestinal perforation, e.g. perforated colonic diverticulitis, abdominal abscess or intestinal fistula within 6 months prior to potential study participation
  • Radiographic evidence of severe portal hypertension/cavernomatous transformation that may, at the discretion of the participating investigators, hamper surgery
  • Other concurrent malignancies except for basal cell cancer of the skin and in-situ cervical cancer
  • Premalignant hematologic disorders, e.g. myelodysplastic syndrome
  • Severe organ dysfunctions (e.g. Liver cirrhosis ≥ Child B; Cardio-pulmonal diseases (NYHA ≥III, arrhythmia Lown III/IV, global respiratory insufficiency); Ascites; Acute pancreatitis; bleeding diathesis, coagulopathy, need for full-dose anticoagulation or INR > 1.5; other severe diseases that might prevent completion of the treatment regimen)
  • Chronic infectious diseases, especially immune deficiency syndromes, e.g. HIV infection, active tuberculosis within 12 months prior to potential study participation
  • History of severe neurologic disorders, e.g. cerebrovascular ischemia
  • History of prior deep venous thrombosis or pulmonary embolism
  • Pregnant or nursing women are ineligible and patients of reproductive potential must agree to use an effective contraceptive method during participation in this trial and for 6 months following the trial
  • Serious medical, psychological, familial, sociological or geographical conditions or circumstances potentially hampering compliance with the study protocol and follow-up Participation in other clinical trials during the last 6 months before allocation to trial

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: neoadj. Treatment
Neoadjuvant CRT with weekly Gemcitabine neoadjuvant 300mg/m2 for 6 weeks combined with external beam radiation (EBRT) delivering a total dose of 50.4 Gy over 28 days in 1.8 Gy fractions will be followed by classical or pylorus-preserving partial pancreato-duodenectomy (PD) and adjuvant chemotherapy (CTx), preferentially using Gemcitabine adjuvant (1000 mg/m2 6 cycles at day 1, 8, 15 of each 28-day cycle).
Radiation: External Beam Radiation
Neoadjuvant CRT with external beam radiation (EBRT) delivering a total dose of 50.4 Gy over 28 days in 1.8 Gy fractions.
Other Names:
  • EBRT
  • External Beam Radiation Therapy
Drug: Gemcitabine neoadjuvant
weekly Gemcitabine 300mg/m2 for 6 weeks neoadjuvant
Other Names:
  • Gemzar
  • Gemcitabin
Procedure: Surgery
Upfront pancreato-duodenectomy
Other Names:
  • Tumor resection
Drug: Gemcitabine adjuvant
Postoperative adjuvant Chemotherapy preferentially using Gemcitabine (1000 mg/m2 6 cycles at day 1, 8, 15 of each 28-day cycle. Administered in both arms, experimental AND active comparator
Other Names:
  • Gemzar
  • Gemcitabin
  • 2',2'-Difluordesoxycytidin
Active Comparator: Upfront Surgery
Upfront PD followed by adjuvant CTx, preferentially with Gemcitabine adjuvant (1000 mg/m2 6 cycles at day 1, 8, 15 of each 28-day cycle).
Procedure: Surgery
Upfront pancreato-duodenectomy
Other Names:
  • Tumor resection
Drug: Gemcitabine adjuvant
Postoperative adjuvant Chemotherapy preferentially using Gemcitabine (1000 mg/m2 6 cycles at day 1, 8, 15 of each 28-day cycle. Administered in both arms, experimental AND active comparator
Other Names:
  • Gemzar
  • Gemcitabin
  • 2',2'-Difluordesoxycytidin

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
3-Year Survival Rate
Time Frame: 3 years after last patient in
Primary outcome measure is the efficacy of neoadjuvant CRT in improving 3-year survival probability from 30% in the control arm undergoing upfront surgery without neoadjuvant CRT to 42% (relative increase of 40%) in the study arm undergoing CRT. The underlying guess of a 30% 3-year survival probability in the control group derives from an assumed median overall survival (MOS) of 20.7 months which corresponds with a MOS of 17.9 months to 23.6 months reported in several randomized trials.
3 years after last patient in

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
R0 Resection rate
Time Frame: 3 days
Histology-proven R0 resection rate based on a standardized histopathological handling of the surgical specimen.
3 days
Frequency of Toxicity Events
Time Frame: three years
Frequency of moderate and severe toxicity events and drop-out rate due to therapy related toxicity (NCI Common Toxicity Criteria v2.0)
three years
Resectability rate
Time Frame: one day
Resectability rate
one day
Rate of intraoperative irregularities
Time Frame: one day
Rate of unexpected intraoperative irregularities, operative time, blood transfusion requirement, postoperative morbidity rate, especially that of pancreatic fistula, and mortality rate
one day
Postoperative Complications
Time Frame: three months
Rate of patients with severe postoperative complications (postoperative recovery > 8 weeks) rendering adjuvant treatment worthless
three months
Disease progression during neoadjuvant therapy
Time Frame: three months
Rate of patients with disease progression during neoadjuvant therapy (only applicable in treatment arm)
three months
Quality of life
Time Frame: three years
Quality of life analysis (EORTC QLQ C30 questionnaire). Assessment of QLQ after completion of neoadjuvant RCTx, after surgery (before hospital discharge) and 6, 12 and 18 months after completion of treatment
three years
Disease-free Survival
Time Frame: three years
Median disease-free survival (DFS, local and distant), overall survival (OS)
three years
First site of tumor recurrence
Time Frame: two years
First site of tumor recurrence as determined by abdominal computed tomography during follow-up study visits
two years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Universitätsklinikum Hamburg-Eppendorf

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Hannover Medical School
Ludwig-Maximilians - University of Munich
Heidelberg University
University of Jena
Technical University of Munich
University Hospital Schleswig-Holstein
University Hospital Freiburg
Universität des Saarlandes
University of Rostock
University Hospital Regensburg
St. Josef Hospital Bochum
SRH Wald-Klinikum Gera GmbH
Klinikum Darmstadt
Staedtisches Klinikum Karlsruhe
University Hospital Augsburg
Klinikum Stuttgart

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Jakob R Izbicki, MD, FACS, Universitätsklinikum Hamburg-Eppendorf

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 1, 2014

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 22, 2016

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 1, 2017

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 27, 2013

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 11, 2013

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 16, 2013

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 11, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 4, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • NEOPA

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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