Clinical trial NCT01716949: Neoadjuvant Chemoradiation With 5-FU(or Capecitabine) and Oxaliplatin Combined With Hyperthermia in Rectal Cancer
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Rectal Cancer
Keywords: rectal cancer
recurrent rectal cancer
hyperthermia
radiation
chemoradiation
5-FU
capecitabine
oxaliplatin
Lead sponsor: University of Erlangen-Nürnberg Medical School
Sponsor class: OTHER
First posted: 2012-10-30
Enrollment: 59
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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
* 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

Primary outcomes:
measure: Feasibility rate (i.e. rate of patients not experiencing dose-limiting toxicity [DLT])
timeFrame: Participants will be followed for the duration of therapy and for 6 weeks after the last study treatment dose (approximately 11 to 12 weeks)
measure: Number of hyperthermia applications by patient
timeFrame: Duration of therapy (approximately 5 to 6 weeks)
Secondary outcomes:
measure: Local progression-free survival
timeFrame: Participants will be followed for up to 5 years after the end of therapy (Follow up period)
measure: Distant metastasis-free survival
timeFrame: Participants will be followed for up to 5 years after the end of therapy (Follow up period)
measure: Overall survival
timeFrame: Participants will be followed for up to 5 years after the end of therapy (Follow up period)
measure: Response rate
timeFrame: Participants will be followed for up to 5 years after the end of therapy (Follow up period)
measure: Rate of R0-resections
timeFrame: 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)
measure: Rate of acute and late toxicity
timeFrame: Participants will be followed for up to 5 years after the end of therapy (Follow up period)
Other outcomes:
Locations:
city: Bad Trissl
country: Germany
facility: Klinik Bad Trissl, Innere Medizin
city: Duesseldorf
country: Germany
facility: University Hospital
city: Erlangen
country: Germany
facility: Universitätsklinikum Erlangen, Strahlenklinik
city: München
country: Germany
facility: LMU München, Campus Großhadern, Medizinische Klinik III, Hyperthermie
city: Oberstaufen
country: Germany
facility: Schlossbergklinik
city: Tübingen
country: Germany
facility: Universitätsklinikum Tübingen, Radioonkologie
Study officials:
affiliation: Strahlenklinik, Universitätsklinikum Erlangen
name: Oliver Ott, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ott OJ, Gani C, Lindner LH, Schmidt M, Lamprecht U, Abdel-Rahman S, Hinke A, Weissmann T, Hartmann A, Issels RD, Zips D, Belka C, Grutzmann R, Fietkau R. Neoadjuvant Chemoradiation Combined with Regional Hyperthermia in Locally Advanced or Recurrent Rectal Cancer. Cancers (Basel). 2021 Mar 13;13(6):1279. doi: 10.3390/cancers13061279.