Hyperthermia European Adjuvant Trial (HEAT)

• ClinicalTrials.gov Identifier: NCT01077427
• Recruitment Status: Unknown
• First Posted: March 1, 2010
• Last Update Posted: November 17, 2017
• Sponsor: Klinikum der Universitaet Muenchen, Grosshadern
• Collaborators: The European Society for Hyperthermic Oncology; Ludwig-Maximilians - University of Munich
• Information provided by (Responsible Party): Rolf D. Issels, Klinikum der Universitaet Muenchen, Grosshadern

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Resected Pancreatic Adenocarcinoma	Device: Gemcitabine + Cisplatin + regional hyperthermia; Drug: Gemcitabine + Capecitabine	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 336 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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)
• Study Start Date: March 2012
• Estimated Primary Completion Date: March 2019
• Estimated Study Completion Date: March 2021

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Disease-free survival (DFS) [ Time Frame: 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 :

1. Overall survival (OS) [ Time Frame: From date of randomization until the date of death from any cause assessed up to 60 months ]

Other Outcome Measures:

1. Toxicity [ Time Frame: Permanent assessment ]
2. Quality of Life [ Time Frame: Permanent assessment ]
   EORTC QLQ C30

Eligibility Criteria

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

Criteria

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"

Contacts and Locations

Contacts

Contact: Rolf D. Issels, MD, PhD; +49-89-4400-77776; heat@med.uni-muenchen.de

Locations

Germany

Klinikum Grosshadern, Medical Center, University of Munich; Recruiting

Munich, Bavaria, Germany, 81377

Contact: Rolf D. Issels, MD, PhD +49-89-4400-77776 heat@med.uni-muenchen.de

Principal Investigator: Rolf D. Issels, MD, PhD

Sponsors and Collaborators

Klinikum der Universitaet Muenchen, Grosshadern

The European Society for Hyperthermic Oncology

Ludwig-Maximilians - University of Munich

Investigators

• Principal Investigator: Rolf D. Issels, MD, PhD; Klinikum Grosshadern, Medical Center, University of Munich, Germany

More Information

Additional Information:

Pankreaszentrum München 

• Responsible Party: Rolf D. Issels, MD, PhD, Klinikum der Universitaet Muenchen, Grosshadern
• ClinicalTrials.gov Identifier: NCT01077427
• Other Study ID Numbers: 115-09; 2008-004802-14 ( EudraCT Number ); AIO-PAK-0111 ( Other Identifier: Arbeitsgemeinschaft Internistische Onkologie (AIO) )
• First Posted: March 1, 2010
• Last Update Posted: November 17, 2017
• Last Verified: November 2017

Keywords provided by Rolf D. Issels, Klinikum der Universitaet Muenchen, Grosshadern:

pancreatic cancer; adjuvant treatment; hyperthermia

Additional relevant MeSH terms:

Hyperthermia; Fever; Body Temperature Changes; Heat Stress Disorders; Wounds and Injuries; Gemcitabine; Capecitabine; Antineoplastic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action