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
Overview
- Phase
- Phase 1
- Intervention
- Radiotherapy
- Conditions
- Rectal Cancer
- Sponsor
- University of Erlangen-Nürnberg Medical School
- Enrollment
- 59
- Locations
- 6
- Primary Endpoint
- Feasibility rate (i.e. rate of patients not experiencing dose-limiting toxicity [DLT])
- Last Updated
- 8 years ago
Overview
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.
Investigators
Eligibility Criteria
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
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
Arms & Interventions
HyRec
Radiotherapy, Hyperthermia, 5-Fluorouracil (may be replaced by Capecitabine), Capecitabine (may be replaced by 5-Fluorouracil), Oxaliplatin
Intervention: Radiotherapy
HyRec
Radiotherapy, Hyperthermia, 5-Fluorouracil (may be replaced by Capecitabine), Capecitabine (may be replaced by 5-Fluorouracil), Oxaliplatin
Intervention: Hyperthermia
HyRec
Radiotherapy, Hyperthermia, 5-Fluorouracil (may be replaced by Capecitabine), Capecitabine (may be replaced by 5-Fluorouracil), Oxaliplatin
Intervention: 5-Fluorouracil
HyRec
Radiotherapy, Hyperthermia, 5-Fluorouracil (may be replaced by Capecitabine), Capecitabine (may be replaced by 5-Fluorouracil), Oxaliplatin
Intervention: Capecitabine
HyRec
Radiotherapy, Hyperthermia, 5-Fluorouracil (may be replaced by Capecitabine), Capecitabine (may be replaced by 5-Fluorouracil), Oxaliplatin
Intervention: Oxaliplatin
Outcomes
Primary Outcomes
Feasibility rate (i.e. rate of patients not experiencing dose-limiting toxicity [DLT])
Time Frame: 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
Time Frame: Duration of therapy (approximately 5 to 6 weeks)
Secondary Outcomes
- Local progression-free survival(Participants will be followed for up to 5 years after the end of therapy (Follow up period))
- Distant metastasis-free 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))
- 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))
- Overall 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))