E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Locally advanced primary or locally recurrent rectal cancer |
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E.1.1.1 | Medical condition in easily understood language |
Locally advanced primary or locally recurrent rectal cancer |
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E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10038051 |
E.1.2 | Term | Rectal cancer stage IV |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10038050 |
E.1.2 | Term | Rectal cancer stage III |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10038046 |
E.1.2 | Term | Rectal cancer recurrent |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10038049 |
E.1.2 | Term | Rectal cancer stage II |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 |
To decide upon the feasibility of a multimodal regimen consisting of radiochemotherapy and hyperthermia |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Age ≥ 18 years
• Histologically confirmed, locally advanced or recurrent (any recurrence of tumor within the lesser pelvis; resectable or non-resectable) or locally advanced adenocarcinoma of the rectum (UICC stage IIB-IV); distant oligo-metastases may be present.
• ECOG-performance status < 2
• Sufficient bone marrow function: WBC > 3,5 x 109/l, Neutrophil granulocytes > 1,5 x 109/l, Platelets > 100 x 109/l, Hemoglobin > 10 g/dl
• Sufficient liver function:, Bilirubin < 2,0 mg%, SGOT, SGPT, alkaline phosphatase, gGT less than 3 times upper limit of normal
• Serum creatinine < 1,5 mg%, glomerular filtration rate (or comparable test) > 50 ml/min
• Signed study-specific consent form prior to therapy
• Fertile patients must use effective contraception during and for 6 months after study treatment
• Considered fit for oxaliplatin and 5-FU-containing combination chemotherapy.
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E.4 | Principal exclusion criteria |
• Pelvic radiotherapy during the last 12 months
• Pregnant or lactating/nursing women
• Drug addiction
• On-treatment participation on other trials
• Active intractable or uncontrollable infection
• Prior or concurrent malignancy (≤ 5 years prior to enrolment in study) except rectal cancer or non-melanoma skin cancer or cervical carcinoma FIGO stage 0-1 if the patient is continuously disease-free
• Chronic diarrhea (> NCI CTC-Grad 1)
• Chronic inflammatory disease of the intestine
• Collagen vascular disease
• The presence of congenital diseases with increased radiation sensitivity, for example ataxia teleangiectatica, or similar
• Pre-existing uncontrolled cardiac disease, signs of cardiac failure, or rhythm disturbances requiring therapy
• Myocardial infarction within the past 12 months
• Congestive heart failure
• Complete bundle branch block
• New York Heart Association (NYHA) class III or IV heart disease
• Known allergic reactions on study medication
• Cardiac pacemaker
• Disease that would preclude chemoradiation or deep regional hyperthermia
• Any metal implants (with exception of non-clustered marker clips)
• Psychological, familial, sociological, or geographical condition that would preclude study compliance
• Patients deemed technically unsatisfactory for deep regional hyperthermia
• Cardiac symptoms (> NCI CTC Grade 1) due to pre-treatment with fluoropyrimidines
• Neurological symptoms (> NCI CTC Grade 1) due to pre-treatment with oxaliplatin
• Rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption
• Oral anticoagulation
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E.5 End points |
E.5.1 | Primary end point(s) |
Phase I/II (59 pat.)
• Feasibility rate (i.e. rate of patients not experiencing dose-limiting toxicity [DLT])
• Number of hyperthermia applications by patient
Amendment Phase II (additional 51 pat. --> 110 pat.)
• Response rate (pCR) according to the RECIST criteria |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
• Local progression-free survival
• Distant metastasis-free survival (excluding M1 patients)
• Overall survival (excluding M1 patients)
• Response rate (RECIST criteria)
• Rate of curative resections (R0)
• Rate of acute and late toxicity according to NCI CTC, and postoperative morbidity
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
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E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 4 |
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
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5 years after the completion of the last patient |
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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 | 10 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |