Hyperthermia With Chemoradiotherapy in Rectal Cancer

NCT06831981 | Recruiting

• 1 other identifier: 182/2024BO1
• Study Type: interventional
• Target: 264
• Locations: 1 country
• Sites: 2

Brief Summary

The goal of this clinical trial is to evaluate the efficacy of deep regional hyperthermia in the context of radiochemotherapy followed by consolidation chemotherapy in locally advanced rectal cancer. Questions it aims to answer are:

• Can surgery be avoided if the tumor completely regresses?
• How high is the Local re-growth rate
• Is the treatment safe?
• Assessment of the Quality of life
• Rate of sphincter-sparing surgery
• Pathological staging, tumor downstaging
• Assessment of continence during the course of therapy Participants will: Undergo radiochemotherapy with or without addition of hyperthermia (50:50 randomisation) followed by standard consolidation chemotherapy. After treatment response evaluation surgery or non-operative management takes place.

Conditions

Rectal Cancer

Keywords

Hyperthermia; TME; high risk rectal tumors; locally advanced retal cancer; total neoadjuvant therapy; organ preservation

Outcome Measures

Primary Outcomes (1)

• Two-year TME-free survival (TMEFS)

  The primary objective of the study is to evaluate the efficacy of deep regional hyperthermia in the context of radiochemotherapy followed by consolidation chemotherapy in locally advanced rectal cancer. As the primary endpoint two-year TME-free survival will be used (TMEFS).

  From September 2024 until September 2036

Study Arms (2)

Radiochemotherapy with hyperthermia followed by consolidation chemotherapy

EXPERIMENTAL

Radiochemotherapy with hyperthermia followed by consolidation chemotherapy. After restaging decision to watch and wait in case of complete or near complete response or surgery

Other: Hyperthermia; Radiation: Radiotherapy; Drug: Chemotherapy with 5-fluorouracil; Drug: Consolidation chemotherapy with FOLFOX

Radiochemotherapy without hyperthermia followed by consolidation chemotherapy

ACTIVE COMPARATOR

Radiochemotherapy without hyperthermia followed by consolidation chemotherapy. After restaging decision to watch and wait in case of complete response or surgery

Radiation: Radiotherapy; Drug: Chemotherapy with 5-fluorouracil; Drug: Consolidation chemotherapy with FOLFOX

Interventions

Hyperthermia OTHER

Additional hyperthermia to radiochemotherapy regime in Arm 1 and radiochemotherapy without additional hyperthermia in Arm 2.

Radiochemotherapy with hyperthermia followed by consolidation chemotherapy

Radiotherapy RADIATION

Radiotherapy of the pelvis

Radiochemotherapy with hyperthermia followed by consolidation chemotherapy; Radiochemotherapy without hyperthermia followed by consolidation chemotherapy

Chemotherapy with 5-fluorouracil DRUG

Chemotherapy with 5-flurouracil is given in parallel to radiotherapy

Radiochemotherapy with hyperthermia followed by consolidation chemotherapy; Radiochemotherapy without hyperthermia followed by consolidation chemotherapy

Consolidation chemotherapy with FOLFOX DRUG

Consolidation chemotherapy with 5-fluorouracil and oxaliplatin

Radiochemotherapy with hyperthermia followed by consolidation chemotherapy; Radiochemotherapy without hyperthermia followed by consolidation chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female patients with histologically confirmed diagnosis of rectal cancer localized 0-12 cm from the anocutaneous line (i.e. lower and middle third of the rectum)
• Indication for total neoadjuvant therapy irrespective of participation in the current study.
• Any MRI staged rectal cancer with one of the following high-risk features:
• cT4
• cN2 (see Appendix)
• Distance to mesorectal fascia 1mm or less.
• Involved Lateral pelvic lymph nodes
• EMVI (extramural venous invasion) positivity
• Staging requirements: High-resolution, thin-sliced (i.e. 3mm) magnetic resonance imaging (MRI) of the pelvis is the mandatory local staging procedure.
• Cross-sectional imaging of the abdomen and chest to exclude distant metastases.
• Aged at least 18 years. No upper age limit.
• WHO/ECOG Performance Status ≤ 1
• Adequate hematological, hepatic, renal and metabolic function parameters
• Informed consent of the patient

You may not qualify if:

• Lower border of the tumor localised more than 12 cm from the anocutaneous line as measured by rigid rectoscopy
• Tumors with microsatellite instability ("MSI-High Tumors") and the possibility for treatment with immune checkpoint inhibition.
• Contraindication for hyperthermia such as metal implants or pacemakers
• Distant metastases (to be excluded by CT scan of the thorax and abdomen)
• Preexisting fecal incontinence for solid stool
• Prior antineoplastic therapy for rectal cancer
• Prior radiotherapy of the pelvic region
• Subject pregnant or breastfeeding, or planning to become pregnant within 6 months after the end of treatment
• Subject (male or female) is not willing to use highly effective methods of contraception (per institutional standard) during treatment and for 6 months (male or female) after the end of treatment (adequate: oral contraceptives, intrauterine device or barrier method in conjunction with spermicidal jelly)
• Other concomitant antineoplastic therapy
• Serious concurrent diseases, including neurologic or psychiatric disorders (incl. dementia and uncontrolled seizures), active, uncontrolled infections, active, disseminated coagulation disorder
• Clinically significant cardiovascular disease (incl. myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) ≤ 6 months before enrolment
• Prior or concurrent malignancy ≤ 3 years prior to enrolment in study (Exception: non-melanoma skin cancer or cervical carcinoma FIGO stage 0-1), if the patient is continuously disease-free
• Known allergic reactions on study medication
• Known dihydropyrimidine dehydrogenase deficiency

Sponsors & Collaborators

• University Hospital Tuebingen: lead
• University Hospital Erlangen: collaborator
• Charite University, Berlin, Germany: collaborator

Study Sites (2)

University Hospital

Tübingen, Baden-Wurttemberg, 72076, Germany

RECRUITING

Universitätsklinikum Tübingen

Tübingen, Baden-Wurttemberg, 72076, Germany

RECRUITING

MeSH Terms

Conditions

Rectal Neoplasms; Hyperthermia

Interventions

Diathermy; Radiotherapy; Drug Therapy; Fluorouracil; Consolidation Chemotherapy; Folfox protocol

Condition Hierarchy (Ancestors)

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; Pathological Conditions, Signs and Symptoms; Heat Stress Disorders; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Hyperthermia, Induced; Therapeutics; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Cihan Gani, MD, Prof. Dr.

  University Hospital Tuebingen

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Cihan Gani, MD, Prof. Dr.

CONTACT

+49 7071 29-82165; cihan.gani@med.uni-tuebingen.de

Barbara Gehler, MD, Dr.

CONTACT

+49 7071 29-82165; barbara.gehler@med.uni-tuebingen.de

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Radiochemotherapy of rectal cancer with (group 1) or without hyperthermia (group 2). Followed by consolidation chemotherapy (six courses). Option for 5x5 short time radiotherapy without hyperthermia followed by nine courses of consolidation chemotherapy.

Study Record Dates

• First Submitted: December 3, 2024
• First Posted: February 18, 2025
• Study Start: September 11, 2024
• Primary Completion (Estimated): June 1, 2036
• Study Completion (Estimated): March 1, 2037
• Last Updated: February 18, 2025

Record last verified: 2024-11

Locations

DE (2)