Hyperthermia European Adjuvant Trial (HEAT)

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)

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.

Study Overview

• Status: Unknown
• Conditions: Resected Pancreatic Adenocarcinoma
• Intervention / Treatment: Drug: Gemcitabine + Capecitabine; Device: Gemcitabine + Cisplatin + regional hyperthermia

• Study Type: Interventional
• Enrollment (Anticipated): 336
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Rolf D. Issels, MD, PhD; Phone Number: +49-89-4400-77776; Email: heat@med.uni-muenchen.de

Study Locations

• Germany
  • Bavaria
    • Munich, Bavaria, Germany, 81377
      • Recruiting
      • Klinikum Grosshadern, Medical Center, University of Munich
      • Contact: Rolf D. Issels, MD, PhD; Phone Number: +49-89-4400-77776; Email: heat@med.uni-muenchen.de
      • Principal Investigator: Rolf D. Issels, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Any ductal adenocarcinoma of the pancreas confirmed by histology
2. Previous R0 or R1 resection of pancreatic tumor with a standardized procedure
3. No other previous or concomitant treatment of pancreatic carcinoma like radiation, neoadjuvant therapy or immunotherapy
4. No tumor recurrence after surgery
5. Performance status ECOG 0-2

6. 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

7. Adequate renal function defined as

   • serum creatinine ≤ 1.2 mg/dL and
   • calculated GFR ≥ 60 mL/min documented within 1 week prior to randomization

8. Adequate coagulatory function defined as

   • Quick-value ≥ 70% and
   • aPTT ≤ 1.5 x ULN documented within 1 week prior to randomization
9. Transaminases (AST, ALT) ≤ 3 x ULN and bilirubin ≤ 2 x ULN documented within 1 week prior to randomization
10. At least 18 years of age
11. 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.)
12. 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)
13. Written informed consent

Exclusion criteria:

1. Cystic carcinoma of the pancreas
2. Periampullary, papillary cancer
3. Metastatic disease
4. Presence of an active infection grade 3 or higher
5. Other severe disease which could impair the patient's ability to participate in the study according to the investigator's opinion
6. Pregnant or breastfeeding women
7. Known allergies or contraindications with regard to substances or procedures of study therapy
8. Severe, non-healing wounds, ulcers or bone fractures
9. 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)
10. Past or current abuse of illegal or legal drugs or alcohol
11. 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).
12. Permanent cardiac pacemaker
13. 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
14. Gross adiposity defined as BMI > 40 kg/m²
15. Treatment with regional hyperthermia not possible for technical reasons (e.g. metal implant)
16. "Known documented dihydropyrimidine dehydrogenase (DPD) deficiency"

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Gemcitabine + Capecitabine	Drug: Gemcitabine + Capecitabine; 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
Experimental: Gemcitabine + Cisplatin + regional hyperthermia	Device: Gemcitabine + Cisplatin + regional hyperthermia; 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

What is the study measuring?

Primary Outcome Measures

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Toxicity		Permanent assessment
Quality of Life	EORTC QLQ C30	Permanent assessment

Collaborators and Investigators

• Sponsor: Klinikum der Universitaet Muenchen, Grosshadern
• Collaborators: Ludwig-Maximilians - University of Munich; The European Society for Hyperthermic Oncology
• Investigators: Principal Investigator: Rolf D. Issels, MD, PhD, Klinikum Grosshadern, Medical Center, University of Munich, Germany

Publications and helpful links

Helpful Links

• Pankreaszentrum München

Study record dates

Study Major Dates

• Study Start: March 1, 2012
• Primary Completion (Anticipated): March 1, 2019
• Study Completion (Anticipated): March 1, 2021

Study Registration Dates

• First Submitted: February 25, 2010
• First Submitted That Met QC Criteria: February 26, 2010
• First Posted (Estimate): March 1, 2010

Study Record Updates

• Last Update Posted (Actual): November 17, 2017
• Last Update Submitted That Met QC Criteria: November 14, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Keywords: pancreatic cancer; hyperthermia; adjuvant treatment
• Additional Relevant MeSH Terms: Wounds and Injuries; Body Temperature Changes; Heat Stress Disorders; Hyperthermia; Fever; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Gemcitabine; Capecitabine
• Other Study ID Numbers: 115-09; 2008-004802-14 (EudraCT Number); AIO-PAK-0111 (Other Identifier: Arbeitsgemeinschaft Internistische Onkologie (AIO))