HEAT: Hyperthermia European Adjuvant Trial

Sponsor

Klinikum der Universitaet Muenchen, Grosshadern (Other)

Overall Status

Unknown status

CT.gov ID

NCT01077427

Collaborator

The European Society for Hyperthermic Oncology (Other), Ludwig-Maximilians - University of Munich (Other)

336

Enrollment

Location

Arms

108

Duration (Months)

3.1

Patients Per Site Per Month

Study Details

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

Anticipated 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 :

Mar 1, 2012

Anticipated Primary Completion Date :

Mar 1, 2019

Anticipated Study Completion Date :

Mar 1, 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

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

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

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

Other Outcome Measures

Toxicity [Permanent assessment]
Quality of Life [Permanent assessment]
EORTC QLQ C30

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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"