Multi-institutional Phase I/II Study:Neoadjuvant chemoradiation with 5-FU (or capecitabine) and oxaliplatin combined with deep regional hyperthermia in locally advanced or recurrent rectal cancer

Phase 1

• Conditions: ocally advanced primary or locally recurrent rectal cancer; MedDRA version: 19.1Level: PTClassification code 10038051Term: Rectal cancer stage IVSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 19.1Level: PTClassification code 10038050Term: Rectal cancer stage IIISystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 19.1Level: PTClassification code 10038046Term: Rectal cancer recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 19.1Level: PTClassification code 10038049Term: Rectal cancer stage IISystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

• Registration Number: EUCTR2009-010093-38-DE
• Lead Sponsor: Dekan of the Medical Faculty of the University Erlangen-Nuremberg; Prof. Dr. Dr. h. c. Jürgen Schüttler

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2012-05-07
• Last Update Posted: 3 April 2017

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: Not specified

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.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 59
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 59

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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To decide upon the feasibility of a multimodal regimen consisting of radiochemotherapy and hyperthermia;Secondary Objective: None;Primary end point(s): Phase I/II (59 pat.)<br>• Feasibility rate (i.e. rate of patients not experiencing dose-limiting toxicity [DLT])<br>• Number of hyperthermia applications by patient<br>Amendment Phase II (additional 51 pat. --> 110 pat.)<br>• Response rate (pCR) according to the RECIST criteria;Timepoint(s) of evaluation of this end point: End of Therapy

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): • Local progression-free survival<br>• Distant metastasis-free survival (excluding M1 patients)<br>• Overall survival (excluding M1 patients)<br>• Response rate (RECIST criteria)<br>• Rate of curative resections (R0)<br>• Rate of acute and late toxicity according to NCI CTC, and postoperative morbidity<br>;Timepoint(s) of evaluation of this end point: End of follow up