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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by University of Erlangen-Nürnberg Medical School
Sponsor:
Information provided by (Responsible Party):
University of Erlangen-Nürnberg Medical School
ClinicalTrials.gov Identifier:
NCT01716949
First received: October 5, 2012
Last updated: July 1, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Rectal Cancer
Radiation: Radiotherapy
Procedure: Hyperthermia
Drug: 5-Fluorouracil
Drug: Capecitabine
Drug: Oxaliplatin
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by University of Erlangen-Nürnberg Medical School:

Primary Outcome Measures:
  • 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) ] [ Designated as safety issue: Yes ]
  • Number of hyperthermia applications by patient [ Time Frame: Duration of therapy (approximately 5 to 6 weeks) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Local progression-free survival [ Time Frame: Participants will be followed for up to 5 years after the end of therapy (Follow up period) ] [ Designated as safety issue: No ]
  • Distant metastasis-free survival [ Time Frame: Participants will be followed for up to 5 years after the end of therapy (Follow up period) ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: Participants will be followed for up to 5 years after the end of therapy (Follow up period) ] [ Designated as safety issue: No ]
  • Response rate [ Time Frame: Participants will be followed for up to 5 years after the end of therapy (Follow up period) ] [ Designated as safety issue: No ]
  • Rate of R0-resections [ Time Frame: 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) ] [ Designated as safety issue: No ]
  • Rate of acute and late toxicity [ Time Frame: Participants will be followed for up to 5 years after the end of therapy (Follow up period) ] [ Designated as safety issue: No ]

Estimated Enrollment: 59
Study Start Date: September 2012
Estimated Study Completion Date: April 2020
Estimated Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: HyRec
Radiotherapy, Hyperthermia, 5-Fluorouracil (may be replaced by Capecitabine), Capecitabine (may be replaced by 5-Fluorouracil), Oxaliplatin
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)
Other Name: all brands of 5-Fluorouracil are allowed
Drug: Capecitabine
1650 mg/m^2/d oral intake d1-14, 22-35 (may be replaced by 5-Fluorouracil)
Other Name: all brands of Capecitabine are allowed
Drug: Oxaliplatin
50 mg/m^2/d as 2-hour bolus infusion on d2, 9, 23, 30
Other Name: all brands of oxaliplatin are allowed

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01716949

Contacts
Contact: Oliver Ott, MD ++49(0)9131-85 ext 33968 st-studiensekretatiat@uk-erlangen.de
Contact: Sebastian Lettmaier, MD ++49(0)9131-85 ext 33968 st-studiensekretariat@uk-erlangen.de

Locations
Germany
Klinik Bad Trissl, Innere Medizin Recruiting
Bad Trissl, Germany, 83080
Principal Investigator: Bernhard Weber, MD         
Sub-Investigator: Friedemann Peschke, MD         
University Hospital Recruiting
Duesseldorf, Germany, 40225
Sub-Investigator: Christiane Matuschek, MD         
Universitätsklinikum Erlangen, Strahlenklinik Recruiting
Erlangen, Germany, 91054
Principal Investigator: Oliver Ott, MD         
Sub-Investigator: Rainer Fietkau, MD         
LMU München, Campus Großhadern, Medizinische Klinik III, Hyperthermie Recruiting
München, Germany, 81377
Principal Investigator: Rolf Issels, MD         
Sub-Investigator: Katharina Lechner, MD         
Schlossbergklinik Recruiting
Oberstaufen, Germany, 87534
Principal Investigator: Thomas Licht, MD         
Sub-Investigator: Blair Wolfgang, MD         
Universitätsklinikum Tübingen, Radioonkologie Recruiting
Tübingen, Germany, 72076
Principal Investigator: Daniel Zips, MD         
Sub-Investigator: Johanna Gellermann, MD         
Sponsors and Collaborators
University of Erlangen-Nürnberg Medical School
Investigators
Principal Investigator: Oliver Ott, MD Strahlenklinik, Universitätsklinikum Erlangen
  More Information

No publications provided

Responsible Party: University of Erlangen-Nürnberg Medical School
ClinicalTrials.gov Identifier: NCT01716949     History of Changes
Other Study ID Numbers: ESHO201107/001
Study First Received: October 5, 2012
Last Updated: July 1, 2014
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by University of Erlangen-Nürnberg Medical School:
rectal cancer
recurrent rectal cancer
hyperthermia
radiation
chemoradiation
5-FU
capecitabine
oxaliplatin

Additional relevant MeSH terms:
Rectal Neoplasms
Fever
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Body Temperature Changes
Signs and Symptoms
Capecitabine
Fluorouracil
Oxaliplatin
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 22, 2014