Neoadjuvant Chemoradiation With 5-FU(or Capecitabine) and Oxaliplatin Combined With Hyperthermia in Rectal Cancer

Phase 1

• Conditions: Rectal Cancer
• Interventions: Radiation: Radiotherapy; Procedure: Hyperthermia; Drug: 5-Fluorouracil; Drug: Capecitabine; Drug: Oxaliplatin

• Registration Number: NCT01716949
• Lead Sponsor: University of Erlangen-Nürnberg Medical School

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2012-09
• Study First Submitted: 2012-10-05
• Study First Submitted QC: 2012-10-25
• Study First Posted: 2012-10-30
• Status Verified: 2017-08
• Last Update Submitted: 2017-08-09
• Last Update Posted: 2017-08-11
• Primary Completion: 2022-06
• Study Completion: 2023-06

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 59

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
HyRec	Radiotherapy	Radiotherapy, Hyperthermia, 5-Fluorouracil (may be replaced by Capecitabine), Capecitabine (may be replaced by 5-Fluorouracil), Oxaliplatin
HyRec	Hyperthermia	Radiotherapy, Hyperthermia, 5-Fluorouracil (may be replaced by Capecitabine), Capecitabine (may be replaced by 5-Fluorouracil), Oxaliplatin
HyRec	Oxaliplatin	Radiotherapy, Hyperthermia, 5-Fluorouracil (may be replaced by Capecitabine), Capecitabine (may be replaced by 5-Fluorouracil), Oxaliplatin
HyRec	5-Fluorouracil	Radiotherapy, Hyperthermia, 5-Fluorouracil (may be replaced by Capecitabine), Capecitabine (may be replaced by 5-Fluorouracil), Oxaliplatin
HyRec	Capecitabine	Radiotherapy, Hyperthermia, 5-Fluorouracil (may be replaced by Capecitabine), Capecitabine (may be replaced by 5-Fluorouracil), Oxaliplatin

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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)

Trial Locations

Locations (6)

LMU München, Campus Großhadern, Medizinische Klinik III, Hyperthermie; 🇩🇪 München, Germany

Klinik Bad Trissl, Innere Medizin; 🇩🇪 Bad Trissl, Germany

Schlossbergklinik; 🇩🇪 Oberstaufen, Germany

Universitätsklinikum Tübingen, Radioonkologie; 🇩🇪 Tübingen, Germany

University Hospital; 🇩🇪 Duesseldorf, Germany

Universitätsklinikum Erlangen, Strahlenklinik; 🇩🇪 Erlangen, Germany