Rectal Cancer
Conditions
Keywords
rectal cancer, recurrent rectal cancer, hyperthermia, radiation, chemoradiation, 5-FU, capecitabine, oxaliplatin
Brief summary
This trial examines the feasibility, effectiveness and safety of a combination of radiotherapy (over a period of five weeks) and chemotherapy (with 5-FU or Capecitabine and Oxaliplatin) and 10 fractions of deep regional hyperthermia in patients with primary locally advanced or locally recurrent rectal cancer. Previous pelvic irradiation in case of a local recurrence is not excluded from the trial. The treatment protocol aims on a preoperatively improved tumor regression allowing less aggressive surgery in primary locally advanced rectal cancer and a higher rate of curative resections in heavily pretreated locally recurrent rectal cancers. Primary endpoint of the trial is the feasibility rate of a multimodal regimen consisting of radiochemotherapy and hyperthermia. Secondary endpoints are local control, survival rates, and toxicity. It is planned to include a total number of 59 patients over a period of 2.5 years.
Interventions
DRUGOxaliplatin
50 mg/m\^2/d as 2-hour bolus infusion on d2, 9, 23, 30
RADIATIONRadiotherapy
45 up to 50.4 Gy; daily dose 1,8 Gy, 5 days per weeks
PROCEDUREHyperthermia
10 sessions, therapeutic time 60 min
DRUG5-Fluorouracil
250 mg/m\^2/d as continuous i.v. infusion on d1-14, 22-35 (may be preplaced by Capecitabine)
DRUGCapecitabine
1650 mg/m\^2/d oral intake d1-14, 22-35 (may be replaced by 5-Fluorouracil)
Sponsors
University of Erlangen-Nürnberg Medical School
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years * Histologically confirmed, locally advanced or recurrent (any recurrence of tumor within the lesser pelvis; resectable or non-resectable) 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 10\^9/l * Neutrophil granulocytes \> 1,5 x 10\^9/l * Platelets \> 100 x 10\^9/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
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 teleangiectatic ataxia, 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 CTCAE Grade 1) due to pretreatment with fluoropyrimidines * Neurological symptoms (\> NCI CTCAE Grade 1) due to pretreatment with oxaliplatin * Rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption * Oral anticoagulation
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Feasibility rate (i.e. rate of patients not experiencing dose-limiting toxicity [DLT]) | Participants will be followed for the duration of therapy and for 6 weeks after the last study treatment dose (approximately 11 to 12 weeks) |
| Number of hyperthermia applications by patient | Duration of therapy (approximately 5 to 6 weeks) |
Secondary
| Measure | Time frame |
|---|---|
| Overall survival | Participants will be followed for up to 5 years after the end of therapy (Follow up period) |
| Response rate | Participants will be followed for up to 5 years after the end of therapy (Follow up period) |
| Local progression-free survival | Participants will be followed for up to 5 years after the end of therapy (Follow up period) |
| Rate of acute and late toxicity | Participants will be followed for up to 5 years after the end of therapy (Follow up period) |
| Rate of R0-resections | Only of participants who are considered as resectable receive surgery in curative intention 4-6 weeks after completion of chemoradiation (results app. after 10 to 12 weeks after start of therapy) |
| Distant metastasis-free survival | Participants will be followed for up to 5 years after the end of therapy (Follow up period) |
Countries
Germany
Contacts
Primary ContactOliver Ott, MD
Backup ContactSebastian Lettmaier, MD
Outcome results
None listed