Effects of Deep Regional Hyperthermia in Patients With Anal Carcinoma Treated by Standard Radiochemotherapy

Study Overview
=================
Brief Summary
-----------------
Randomized study to investigate the efficacy of deep regional hyperthermia in patients with anal carcinoma treated by standard radiochemotherapy with MMC and 5-FU.

Detailed Description
-----------------
Pat. with anal carcinoma and treated with standard radiochemotherapy with Mitomycin C and 5-FU will in the experimental arm receive deep regional hyperthermia (6x).

Official Title
-----------------
Randomized Trial to Evaluate Effects of Deep Regional Hyperthermia in Patients With Anal Carcinoma Treated by Standard Radiochemotherapy

Conditions
-----------------
Anal Carcinoma

Intervention / Treatment
-----------------
* Radiation: Irradiation
* Drug: Mitomycin C
* Drug: 5-Fluorouracil
* Procedure: Hyperthermia


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically proven anal squamous cell carcinoma (SCC) (WHO 2004), including anal canal carcinoma (UICC 2002) and anal margin carcinoma (UICC 2002) All stages except T1 N0 M0 after local excision (UICC 2002) Age ≥ 18 years ECOG Status 0-1 Patients that have understand protocol and signed informed consent form Sufficient bone marrow function: WBC ≥ 3,0 x 10^9/l, Platelets ≥ 100 x 10^9/l, Hemoglobin ≥ 10 g/dl Sufficient liver function: Bilirubin < 1,5 mg/dl, SGOT, SGPT, alkaline phosphatase, gGT less than 3 times upper limit of normal Exclusion Criteria: Stage T1 N0 M0 after local excision (UICC 2002) Uncontrolled, severe cardiac dysfunction (NYHA III/IV) 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 Chronic inflammatory disease of the intestine Active intractable or uncontrolled infection Chronic diarrhea ( > NCI CTC-Grad 1) Acute thrombosis Collagen vascular disease Cardiac pacemaker HIV-infection; Patients with hepatitis A or B virus infection, with HPV infection or Patients receiving immune suppressive treatment can be included Devices that preclude deep regional hyperthermia (Endoprosthesis, stent in vascular system, acute thrombosis) Any metal implants (with exception of non-clustered marker clips) Conditions that preclude the application of fractionated pelvic radiotherapy Conditions that preclude regular follow-up Pregnant or breast feeding women Prior pelvic radiotherapy Prior chemotherapy Drug addiction On-treatment participation on other trials Prior or concurrent malignancy or leucemia (≤ 5 years prior to enrolment in study) except anal cancer or non-melanoma skin cancer or cervical carcinoma FIGO stage 0-1 if the patient is continuously disease-free The presence of increased radiation sensitivity, for example ataxia teleangiectatica, or similar Psychological, familial, sociological, or geographical condition that would preclude study compliance

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: control arm<br>Irradiation 1.8Gy/d; T2N0 55.8Gy; T3N0-T4N0 59.4Gy Chemotherapy: Mitomycin C 10mg/m^2/d on d1 and 29; 5-Fluorouracil 1000mg/m^2/d on d1-5, 29-33 | Radiation: Irradiation<br>* Radiotherapy 55,8 Gy - 59,4 Gy<br>Drug: Mitomycin C<br>* MMC w1, w5<br>* Other names: any brand is permitted;Drug: 5-Fluorouracil<br>* 5-FU w1, w5<br>* Other names: any brand is permitted;|
| Experimental: Experimental arm<br>Irradiation 1.8Gy/d; T2N0 55.8Gy; T3N0-T4N0 59.4Gy Chemotherapy: Mitomycin C 10mg/m^2/d on d1 and 29; 5-Fluorouracil 1000mg/m^2/d on d1-5, 29-33 Hyperthermia: 6 | Radiation: Irradiation<br>* Radiotherapy 55,8 Gy - 59,4 Gy<br>Drug: Mitomycin C<br>* MMC w1, w5<br>* Other names: any brand is permitted;Drug: 5-Fluorouracil<br>* 5-FU w1, w5<br>* Other names: any brand is permitted;Procedure: Hyperthermia<br>* 6x deep regional hyperthermia<br>* Other names: Deep regional hyperthermia;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement of complete remission |  | 12 weeks after start of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Colostomy-free survival |  | 5 years after start of treatment | 
| locoregional relapse-free survival |  | 5 years after start of treatment | 
| Overall relapse-free survival |  | 5 years after start of treatment | 
| Overall survival |  | 5 years after start of treatment | 
| Response rate |  | 5 years after start of treatment | 
| Rate of acute and late toxicity |  | 5 years after start of treatment | 
| Quality of life |  | 5 years after start of treatment | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
anal carcinoma, hyperthermia, radiotherapy, chemotherapy, radiochemotherapy