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Safety of multimodality treatment with a combination of intraoperative Chemotherapy and surgical Resection in locally confined or borderline resectable pancreatic cancer

Organizational Data

DRKS-ID:
DRKS00015766
Recruitment Status:
Recruiting ongoing
Date of registration in DRKS:
2018-10-23
Last update in DRKS:
2019-11-14
Registration type:
Prospective

Acronym/abbreviation of the study

combiCaRe

URL of the study

No Entry

Brief summary in lay language

Pancreatic cancer is one of the most aggressive malignant diseases, which is mostly diagnosed at an advanced stage. Despite large research efforts its prognosis is still very poor. Complete tumor resection followed by "adjuvant" chemotherapy remains the only curative option for pancreatic cancer patients. However, even after potentially curative resection the 5-year survival rate remains below 20%, due to local recurrence and growth of tumor cells at distant sites. The causes of recurrence after surgical resection are incompletely understood. It has been supposed that pancreatic cancer early forms metastases and tumor cell dissemination also occurs during surgery. A perioperative chemotherapeutic regime might diminish the systemic tumor spread, improving long-term survival. Therefore, within the proposed clinical trial a chemotherapy, which combats tumor growth, will be administered during the surgical procedure. Initially, the safety of the perioperative chemotherapeutic regimen will be evaluated, and the effect of the anti-tumor agent on tumor cell dissemination during the surgical manipulation of the tumor will be analyzed.

Brief summary in scientific language

With a 5-year survival of about 7%, the prognosis of pancreatic cancer is very poor despite tremendous research efforts. In addition, mortality is projected to further increase, making PDAC the 2nd leading cause of cancer-related death by 2020 according to the Pancreatic Cancer Action Network. Complete surgical tumor resection followed by adjuvant chemotherapy is currently the only curative treatment option. However, even after potentially curative R0-resection the 5-year survival rate remains below 20%. Although several studies have shown that chemotherapeutic regimens increase overall survival in the adjuvant setting, still long-term survival is rare, due to early recurrence and metastases. The mechanisms of which are only partially understood. It has been assumed that subclinical metastases might occur early during tumor development, but iatrogenic tumor cell dissemination as a result of tumor manipulation during surgery is also a concern. Intraoperative chemotherapy may diminish local, distant and circulating minimal residual disease and thus reduce the risk of local and systemic recurrence, leading to an increased overall survival. The primary purpose of the present pilot feasibility trial is to evaluate the toxicity, potential side effects and adverse events related to short-term systemic chemotherapy and surgical trauma. In addition, the effects of the perioperative chemotherapeutic regime on tumor cell dissemination via the blood stream during the surgical manipulation of the pancreas will be analyzed. In case of clinical safety and efficacy against disseminated tumor cells a consecutive clinical trial investigating the oncologic benefit of this multimodal treatment will be conducted.

Health condition or problem studied

Free text:
(Borderline) Resectable ductal adenocarcinoma of the pancreatic head
ICD10:
C25.0 - Head of pancreas
Healthy volunteers:
No Entry

Interventions, Observational Groups

Arm 1:
Perioperative chemotherapy with 5-Fluoruracil (5-FU) and calcium folinate, (Partial) pancreaticoduodenectomy; Chemotherapy with 5-FU is started one day prior to surgery and continued until postoperative day 1. Overall, 1000 mg/m² per day are applied i.v. for 48 hours (total dose 2000 mg/m²). Immediately prior to 5-FU 400 mg/m2 calcium folinate will be given i.v. over 2 hours.
Arm 2:
(Partial) pancreaticoduodenectomy (matched historical controls)

Endpoints

Primary outcome:
30-day complication rate according to the Clavien-Dindo classification
Secondary outcome:
60-day complication rate according to the Clavien-Dindo classification; 30-and 60-day mortality; pancreas-associated postoperative morbidity: postoperative pancreatic fistula (POPF, according to the ISGPS classification), intraabdominal fluid-collection or abscess, delayed gastric emptying (DGE) and postpancreatectomy hemorrhage (according to the ISGPS definitions); bile leakage; perioperative bleeding; gastrointestinal bleeding; postoperative ileus; duration of intensive care unit (ICU) stay (postoperative and readmissions); postoperative duration of hospital stay; need for readmission; anemia (Hb < 8 g/dl), thrombocytopenia, leukopenia; postoperative sepsis; allergic reactions; serotonin syndrome; mucositis (stomatitis, cheilitis, esophagitis, proctitis), diarrhea, nausea, vomiting; alopecia, hand-and-foot syndrome; central neurotoxicity, peripheral neuropathy; renal failure (serum creatinine, BUN, urine production); liver damage (AST > 5 x ULN, ALT > 5 x ULN, AP > 5 x ULN, GGT, bilirubine > 1.5 x ULN); cardiotoxicity (continuous ECG Monitoring during and until 24 hours post perioperative chemotherapy); bronchospasm; perioperative tumor cell dissemination (circulating tumor cells, CTCs); pharmacokinetics of perioperative chemotherapy

Study Design

Purpose:
Treatment
Allocation:
Non-randomized controlled study
Control:
  • Historical
Phase:
I-II
Study type:
Interventional
Mechanism of allocation concealment:
No Entry
Blinding:
No
Assignment:
Other
Sequence generation:
No Entry
Who is blinded:
No Entry

Recruitment

Recruitment Status:
Recruiting ongoing
Reason if recruiting stopped or withdrawn:
No Entry

Recruitment Locations

Recruitment countries:
  • Germany
Number of study centers:
Monocenter study
Recruitment location(s):
  • University medical center Chirurgische Klinik, Abteilung für Allgemein-, Viszeral-und Transplantationschirurgie Heidelberg

Recruitment period and number of participants

Planned study start date:
2019-05-17
Actual study start date:
2019-07-11
Planned study completion date:
No Entry
Actual Study Completion Date:
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Target Sample Size:
40
Final Sample Size:
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Inclusion Criteria

Sex:
All
Minimum Age:
18 Years
Maximum Age:
75 Years
Additional Inclusion Criteria:
newly diagnosed, resectable or borderline resectable pancreatic cancer located in the head of the pancreas, without arterial involvement, on cross-sectional Imaging (contrast enhanced CT scan) according to the International Study Group of Pancreatic Surgery (ISGPS) criteria; histologically or cytologically proven pancreatic ductal adenocarcinoma (including variants); ≥18 and ≤75 years of age; informed consent; Eastern Cooperative Oncology Group (ECOG) Performance status 0-2; patient considered to tolerate surgery and chemotherapy by a multidisciplinary team; women of childbearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation

Exclusion Criteria

distant metastatic disease; renal disease, creatinine clearance < 50 ml/min (estimated by Cockroft-Gault); abnormal hepatic function as defined by a total bilirubine level > 1.5 x the upper limit of normal (ULN), unless the patient has extrahepatic cholestasis due to pancreatic cancer, or alanine aminotransferase (ALT) > 2.5 x ULN, liver cirrhosis (of any Child-Pugh grade); serious cardiovascular disease (e.g. myocardial infarction in the last 12 months, congestive heart failure NYHA III/IV, unstable angina pectoris); severe COPD, GOLD stage > II; American Society of Anesthesiologists (ASA) score > III; active infection, including cholangitis; abnormal bone marrow function, defined as an absolute white blood cell count < 3/nl or platelet count < 100/nl; pernicious anemia or other megaloblastic anemias where Vitamin B12 is deficient; immunosuppressive therapy; allergy or known intolerance to 5-FU or calcium folinate; patients with a known lack of dihydropyrimidinedehydrogenase (DPD)-activity or patients treated with DPD inhibitors such as brivudine; current pregnancy or breastfeeding; history of another malignancy in the past 5 years; inability to comply with study and/or follow-up procedures; (language) problems in understanding the patient information document explaining the present clinical trial; concurrent participation in another clinical study; any condition which could result in an undue risk for the patient in the opinion of the investigator

Addresses

Primary Sponsor

Universitätsklinikum Heidelberg
Im Neuenheimer Feld 672
69120 Heidelberg
Germany
Telephone:
No Entry
Fax:
No Entry
Contact per E-Mail
URL:
http://www.klinikum.uni-heidelberg.de
Investigator Sponsored/Initiated Trial (IST/IIT):
Yes

Contact for Scientific Queries

Chirurgische Klinik, Abteilung für Allgemein-, Viszeral-und Transplantationschirurgie, Universitätsklinikum Heidelberg
Prof. Dr. Thilo Hackert
Im Neuenheimer Feld 110
69120 Heidelberg
Germany
Telephone:
00496221565150
Fax:
00496221565969
Contact per E-Mail
URL:
No Entry

Contact for Public Queries

Chirurgische Klinik, Abteilung für Allgemein-, Viszeral-und Transplantationschirurgie, Universitätsklinikum Heidelberg
Dr. Dr. Susanne Roth
Im Neuenheimer Feld 110
69120 Heidelberg
Germany
Telephone:
00496221565150
Fax:
00496221565969
Contact per E-Mail
URL:
No Entry

Principal Investigator

Chirurgische Klinik, Abteilung für Allgemein-, Viszeral-und Transplantationschirurgie, Universitätsklinikum Heidelberg
Prof. Dr. Thilo Hackert
Im Neuenheimer Feld 110
69120 Heidelberg
Germany
Telephone:
00496221565150
Fax:
00496221565969
Contact per E-Mail
URL:
No Entry

Sources of Monetary or Material Support

Private sponsorship (foundations, study societies, etc.)

Heidelberger Stiftung Chirurgie
Im Neuenheimer Feld 110
69120 Heidelberg
Germany
Telephone:
No Entry
Fax:
No Entry
Contact per E-Mail
URL:
No Entry

Ethics Committee

Address Ethics Committee

Ethikkommission der Medizinischen Fakultät Heidelberg
Alte Glockengießerei 11/1
69115 Heidelberg
Germany
Telephone:
+49-6221-338220
Fax:
+49-6221-3382222
Contact per E-Mail
URL:
No Entry

Vote of leading Ethics Committee

Date of ethics committee application:
2018-04-23
Ethics committee number:
AFmo-269/2018
Vote of the Ethics Committee:
Approved
Date of the vote:
2018-09-11

Further identification numbers

Other primary registry ID:
No Entry
EudraCT Number:
2017-000374-12
UTN (Universal Trial Number):
No Entry
EUDAMED Number:
No Entry

IPD - Individual Participant Data

Do you plan to make participant-related data (IPD) available to other researchers in an anonymized form?:
No Entry
IPD Sharing Plan:
No Entry

Study protocol and other study documents

Study protocols:
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Study abstract:
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Other study documents:
No Entry
Background literature:
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Related DRKS studies:
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Publication of study results

Planned publication:
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Publikationen/Studienergebnisse:
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Date of first publication of study results:
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DRKS entry published for the first time with results:
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Basic reporting

Basic Reporting / Results tables:
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Brief summary of results:
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