Hyperthermia European Adjuvant Trial

Study Overview
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Brief Summary
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Improvement of the clinical outcome in patients with resectable pancreatic carcinoma through an intensified adjuvant treatment with gemcitabine, cisplatin and regional deep hyperthermia as compared to standard chemotherapy.

Official Title
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A Randomized Two-armed Open Study on the Adjuvant Therapy in Patients With R0/R1 Resected Pancreatic Carcinoma With Gemcitabine Plus Capecitabine (Arm GC) vs. Gemcitabine Plus Cisplatin With Regional Hyperthermia (Arm GPH)

Conditions
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Resected Pancreatic Adenocarcinoma

Intervention / Treatment
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* Device: Gemcitabine + Cisplatin + regional hyperthermia
* Drug: Gemcitabine + Capecitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Any ductal adenocarcinoma of the pancreas confirmed by histology Previous R0 or R1 resection of pancreatic tumor with a standardized procedure No other previous or concomitant treatment of pancreatic carcinoma like radiation, neoadjuvant therapy or immunotherapy No tumor recurrence after surgery Performance status ECOG 0-2 Adequate bone marrow function defined as WBC count ≥ 3.5 x 109/L and platelets ≥ 150 x 109/L and haemoglobin ≥ 9 g/dl documented within 1 week prior to randomization Adequate renal function defined as serum creatinine ≤ 1.2 mg/dL and calculated GFR ≥ 60 mL/min documented within 1 week prior to randomization Adequate coagulatory function defined as Quick-value ≥ 70% and aPTT ≤ 1.5 x ULN documented within 1 week prior to randomization Transaminases (AST, ALT) ≤ 3 x ULN and bilirubin ≤ 2 x ULN documented within 1 week prior to randomization At least 18 years of age Women with childbearing potential and fertile men must use adequate contraceptive measures during and for at least 3 months (female) and 6 months (male) after completion of study therapy (Adequate methods for women are oral contraceptives with estrogen and progesterone, vaginal rings, contraceptive patches, estrogen-free ovulation inhibitors, intrauterine devices with progesterone, 3-month injections with depot progesterone, implants setting free progesterone, abstinence or sterilization (vasectomy) of the male partner. Men must use condoms.) Women with childbearing potential must have a negative pregnancy test within 1 week prior to randomization (postmenopausal women with amenorrhea for more than 1 year are regarded as having no childbearing potential) Written informed consent Exclusion criteria: Cystic carcinoma of the pancreas Periampullary, papillary cancer Metastatic disease Presence of an active infection grade 3 or higher Other severe disease which could impair the patient's ability to participate in the study according to the investigator's opinion Pregnant or breastfeeding women Known allergies or contraindications with regard to substances or procedures of study therapy Severe, non-healing wounds, ulcers or bone fractures Participation in another clinical trial during this study or within 4 weeks prior to randomization (Exception: participation in a surgical trial prior to this study, for instance RECOPANC trial, comparing two different surgical procedures of pancreas resection) Past or current abuse of illegal or legal drugs or alcohol Other primary malignant diseases in the medical history during the last 5 years (exceptions: carcinoma in situ of the cervix or adequately treated basal cell carcinoma of the skin). Permanent cardiac pacemaker Clinically significant cardiovascular or vascular disease or disorder ≤ 6 months before study enrolment (e.g. myocardial infarction, unstable angina pectoris, chronic heart failure NYHA ≥ grade 2, uncontrolled arrhythmia, cerebral infarction Gross adiposity defined as BMI > 40 kg/m² Treatment with regional hyperthermia not possible for technical reasons (e.g. metal implant) Known documented dihydropyrimidine dehydrogenase (DPD) deficiency

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Gemcitabine + Capecitabine<br> | Drug: Gemcitabine + Capecitabine<br>* Gemcitabine: 1000 mg/m² as iv-infusion on days 1, 8 and 15 of each course (Total dose: 18 g/m²) Capecitabine: daily dose of 1660 mg/m²; administered orally for 21 days followed by 7 days' rest (one cycle) for six cycles<br>|
| Experimental: Gemcitabine + Cisplatin + regional hyperthermia<br> | Device: Gemcitabine + Cisplatin + regional hyperthermia<br>* Gemcitabine: 1000 mg/m² as iv-infusion on days 1 and 15 of each course (Total dose: 12 g/m²) Cisplatin: 25 mg/m² as iv-infusion on days 2, 3* and 16, 17* of each course (Total dose: 600 mg/m²) Regional hyperthermia: 60 minutes on days 2, 3*, and 16, 17* of each course * as an exception for medical or logistic reasons RHT and cisplatin can be applied day 4 instead of 3 and day 18 instead of 17<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-free survival (DFS) |  | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) |  | From date of randomization until the date of death from any cause assessed up to 60 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pancreatic cancer, adjuvant treatment, hyperthermia