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

• ClinicalTrials.gov Identifier: NCT01716949
• Recruitment Status: Recruiting
• First Posted: October 30, 2012
• Last Update Posted: August 11, 2017
• Sponsor: University of Erlangen-Nürnberg Medical School
• Information provided by (Responsible Party): University of Erlangen-Nürnberg Medical School

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Rectal Cancer	Radiation: Radiotherapy; Procedure: Hyperthermia; Drug: 5-Fluorouracil; Drug: Capecitabine; Drug: Oxaliplatin	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 59 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (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
• Study Start Date: September 2012
• Estimated Primary Completion Date: June 2022
• Estimated Study Completion Date: June 2023

Arms and Interventions

Arm

Intervention/treatment

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

Outcome Measures

Primary Outcome Measures :

1. 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) ]
2. Number of hyperthermia applications by patient [ Time Frame: Duration of therapy (approximately 5 to 6 weeks) ]

Secondary Outcome Measures :

1. Local progression-free survival [ Time Frame: Participants will be followed for up to 5 years after the end of therapy (Follow up period) ]
2. Distant metastasis-free survival [ Time Frame: Participants will be followed for up to 5 years after the end of therapy (Follow up period) ]
3. Overall survival [ Time Frame: Participants will be followed for up to 5 years after the end of therapy (Follow up period) ]
4. Response rate [ Time Frame: Participants will be followed for up to 5 years after the end of therapy (Follow up period) ]
5. 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) ]
6. 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) ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

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

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: University of Erlangen-Nürnberg Medical School
• ClinicalTrials.gov Identifier: NCT01716949
• Other Study ID Numbers: ESHO201107/001
• First Posted: October 30, 2012
• Last Update Posted: August 11, 2017
• Last Verified: August 2017

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:

Hyperthermia; Fever; Rectal Neoplasms; 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; Heat Stress Disorders; Wounds and Injuries; Fluorouracil; Capecitabine; Oxaliplatin; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs