E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
R0/R1 resected ductal pancreatic adenocarcinoma |
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E.1.1.1 | Medical condition in easily understood language |
R0/R1 resected ductal pancreatic adenocarcinoma |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10033602 |
E.1.2 | Term | Pancreatic adenocarcinoma resectable |
E.1.2 | System Organ Class | 100000004864 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10051971 |
E.1.2 | Term | Pancreatic adenocarcinoma |
E.1.2 | System Organ Class | 100000004864 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Improvement of the outcome of resectable pancreatic carcinoma through an as compared to standard therapy intensified adjuvant treamtent with gemcitabine, cisplatin and regional deep hyperthermia |
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E.2.2 | Secondary objectives of the trial |
Comparison of the both treatment arms with regard to
– overall survival (OS)
– quality of life
- toxicity profile
|
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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. Postoperative tumor marker (CEA/CA19-9) ≤ 2.5 x upper limit of normal (ULN)
to be documented within 1 week prior to randomization
6. Performance status ECOG 0-2
7. Adequate bone marrow function defined as
- WBC count ≥ 3.5 x 10^9/L and
- platelets ≥ 150 x 10^9/L and
- haemoglobin ≥ 9 g/dl
documented within 1 week prior to randomization
8. Adequate renal function defined as
- serum creatinine ≤ 1.2 mg/dL and
- calculated GFR ≥ 60 mL/min documented within 1 week prior to randomization
9. Adequate coagulatory function defined as
- Quick-value ≥ 70% and
- aPTT ≤ 1.5 x ULN
documented within 1 week prior to randomization
10. Transaminases (AST, ALT) ≤ 3 x ULN and bilirubin ≤ 2 x ULN documented within 1 week prior to randomization
11. At least 18 years of age
12. 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.)
13. 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)
14. Written informed consent
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E.4 | Principal 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 </= 6months 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 |
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E.5 End points |
E.5.1 | Primary end point(s) |
Comparison of disease free survival (DSF) in both treatment arms (GPH and G) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Tumor assessments will be done after course 3 or if disease recurrence is suspected, at the end of the study (= 4 weeks after the final dose) and at 3 monthly intervals during Follow Up. |
|
E.5.2 | Secondary end point(s) |
Comparison of the both treatment arms with regard to:
- overall survival
- quality of life
- toxicity profile |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
- Overall survival will be evaluated during treatment on D1, 2, 3, 8, 15, 16, 17 and 22 of every 28 day-course, at the end of the study (= 4 weeks after last dose) and at 3 monthly intervals during Follow Up.
- Quality of life will be evaluated during treatment on D1 and D15, at the end of the study and at 3 monthly intervals during Follow Up
- Toxicity profile will be evaluated during treatment on D1, 2, 3, 8, 15, 16, 17 and 22 of every 28 day-course and at the end of the study |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
treatment scheme with hyperthermia |
|
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 25 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
Six treatment courses will be administered unless one of the following occurs:
– disease recurrence,
– unacceptable toxicity,
– patient’s wish,
– other conditions under which continuation of treatment is not in the patient’s best interest according to the investigator’s opinion.
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |