Neoadjuvant Treatment in Resectable Pancreatic Cancer

NCT01900327 | Terminated Phase 3 DMC

• 1 other identifier: NEOPA
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 16

Brief Summary

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

Conditions

Pancreatic Cancer

Keywords

pancreatic cancer; surgery; chemoradiation; neoadjuvant treatment; overall survival

Outcome Measures

Primary Outcomes (1)

• 3-Year Survival Rate

  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 Outcomes (9)

• R0 Resection rate

  3 days

• Frequency of Toxicity Events

  three years

• Resectability rate

  one day

• Rate of intraoperative irregularities

  one day

• Postoperative Complications

  three months

Study Arms (2)

neoadj. Treatment

EXPERIMENTAL

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; Drug: Gemcitabine neoadjuvant; Procedure: Surgery; Drug: Gemcitabine adjuvant

Upfront Surgery

ACTIVE COMPARATOR

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; Drug: Gemcitabine adjuvant

Interventions

External Beam Radiation RADIATION

Neoadjuvant CRT with external beam radiation (EBRT) delivering a total dose of 50.4 Gy over 28 days in 1.8 Gy fractions.

Also known as: External Beam Radiation Therapy, EBRT

neoadj. Treatment

Gemcitabine neoadjuvant DRUG

weekly Gemcitabine 300mg/m2 for 6 weeks neoadjuvant

Also known as: Gemcitabin, Gemzar

neoadj. Treatment

Surgery PROCEDURE

Upfront pancreato-duodenectomy

Also known as: Tumor resection

Upfront Surgery; neoadj. Treatment

Gemcitabine adjuvant DRUG

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

Also known as: Gemcitabin, Gemzar, 2',2'-Difluordesoxycytidin

Upfront Surgery; neoadj. Treatment

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Universitätsklinikum Hamburg-Eppendorf: lead
• University Hospital Schleswig-Holstein: collaborator
• Hannover Medical School: collaborator
• St. Josef Hospital Bochum: collaborator
• University of Jena: collaborator
• SRH Wald-Klinikum Gera GmbH: collaborator
• Klinikum Darmstadt: collaborator
• Universität des Saarlandes: collaborator
• Heidelberg University: collaborator
• Staedtisches Klinikum Karlsruhe: collaborator
• University Hospital Freiburg: collaborator
• University Hospital Regensburg: collaborator
• Technical University of Munich: collaborator
• University Hospital Augsburg: collaborator
• Klinikum Stuttgart: collaborator
• Ludwig-Maximilians - University of Munich: collaborator
• University of Rostock: collaborator

Study Sites (16)

University Freiburg

Freiburg im Breisgau, Baden-Wurttemberg, 79106, Germany

Location

Heidelberg University

Heidelberg, Baden-Wurttemberg, 69120, Germany

Location

Technische Universität München

München, Bavaria, 81675, Germany

Location

University Regensburg

Regensburg, Bavaria, 93053, Germany

Location

Klinikum Augsburg

Augsburg, Bayer, 86156, Germany

Location

Klinikum Darmstadt

Darmstadt, Hesse, 64283, Germany

Location

Hannover Medical School

Hanover, Lower Saxony, 30625, Germany

Location

University of Rostock

Rostock, Mecklenburg-Vorpommern, 18057, Germany

Location

St. Joseph Hospital Bochum

Bochum, North Rhine-Westphalia, 44791, Germany

Location

Saarland University

Homburg, Saarland, 66421, Germany

Location

University of Schleswig-Holstein Kiel

Kiel, Schleswig-Holstein, 24105, Germany

Location

University of Schleswig-Holstein Lübeck

Lübeck, Schleswig-Holstein, 23538, Germany

Location

Klinikum Gera

Gera, Thuringia, 07548, Germany

Location

University of Jena

Jena, Thuringia, 07747, Germany

Location

University Medical Center Hamburg-Eppendorf

Hamburg, 20246, Germany

Location

Klinikum Karlsruhe

Karlsruhe, 76133, Germany

Location

Related Publications (1)

• Tachezy M, Gebauer F, Petersen C, Arnold D, Trepel M, Wegscheider K, Schafhausen P, Bockhorn M, Izbicki JR, Yekebas E. Sequential neoadjuvant chemoradiotherapy (CRT) followed by curative surgery vs. primary surgery alone for resectable, non-metastasized pancreatic adenocarcinoma: NEOPA- a randomized multicenter phase III study (NCT01900327, DRKS00003893, ISRCTN82191749). BMC Cancer. 2014 Jun 7;14:411. doi: 10.1186/1471-2407-14-411.

  PMID: 24906700 DERIVED

Related Links

• Homepage University Medical Center

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Gemcitabine; Surgical Procedures, Operative; Transurethral Resection of Bladder

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Urologic Surgical Procedures; Urogenital Surgical Procedures

Study Officials

• Jakob R Izbicki, MD, FACS

  Universitätsklinikum Hamburg-Eppendorf

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 27, 2013
• First Posted: July 16, 2013
• Study Start: February 1, 2014
• Primary Completion: November 22, 2016
• Study Completion: July 1, 2017
• Last Updated: May 11, 2018

Record last verified: 2018-05

Locations

DE (16)