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

Rectal Cancer Clinical Trial

— HyRec  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01716949
• Other study ID #: ESHO201107/001
• Status: Recruiting
• Phase: Phase 1/Phase 2
• First received: October 5, 2012
• Last updated: August 9, 2017
• Start date: September 2012
• Est. completion date: June 2023

Study information

• Verified date: August 2017
• Source: University of Erlangen-Nürnberg Medical School
• Contact: Oliver Ott, MD
• Phone: ++49(0)9131-85
• Email: st-studiensekretatiat[@]uk-erlangen.de
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 59
• Est. completion date: June 2023
• Est. primary completion date: June 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Fever
• Rectal Cancer
• Rectal Neoplasms

Intervention

Radiation:
• Radiotherapy
45 up to 50.4 Gy; daily dose 1,8 Gy, 5 days per weeks

Procedure:
• Hyperthermia
10 sessions, therapeutic time 60 min

Drug:
• 5-Fluorouracil
250 mg/m^2/d as continuous i.v. infusion on d1-14, 22-35 (may be preplaced by Capecitabine)
• Capecitabine
1650 mg/m^2/d oral intake d1-14, 22-35 (may be replaced by 5-Fluorouracil)
• Oxaliplatin
50 mg/m^2/d as 2-hour bolus infusion on d2, 9, 23, 30

Locations

Country	Name	City	State
Germany	Klinik Bad Trissl, Innere Medizin	Bad Trissl
Germany	University Hospital	Duesseldorf
Germany	Universitätsklinikum Erlangen, Strahlenklinik	Erlangen
Germany	LMU München, Campus Großhadern, Medizinische Klinik III, Hyperthermie	München
Germany	Schlossbergklinik	Oberstaufen
Germany	Universitätsklinikum Tübingen, Radioonkologie	Tübingen

Sponsors (1)

Lead Sponsor	Collaborator
University of Erlangen-Nürnberg Medical School

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	Number of hyperthermia applications by patient		Duration of therapy (approximately 5 to 6 weeks)
Secondary	Local progression-free survival		Participants will be followed for up to 5 years after the end of therapy (Follow up period)
Secondary	Distant metastasis-free survival		Participants will be followed for up to 5 years after the end of therapy (Follow up period)
Secondary	Overall survival		Participants will be followed for up to 5 years after the end of therapy (Follow up period)
Secondary	Response rate		Participants will be followed for up to 5 years after the end of therapy (Follow up period)
Secondary	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)
Secondary	Rate of acute and late toxicity		Participants will be followed for up to 5 years after the end of therapy (Follow up period)