Hyperthermia with Chemoradiotherapy in Rectal Cancer (ARO 2024-13)

February 12, 2025 updated by: University Hospital Tuebingen

Radiochemotherapy with Concomitant Deep Regional Hyperthermia in Locally Advanced Rectal Cancer. a Prospective, Randomized Phase III Trial.

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

In this prospective, randomized phase III trial "Radiochemotherapy with concomitant deep regional hyperthermia in locally advanced rectal cancer" trial it is hypothesized that with the addition of hyperthermia complete response rates can be further increased resulting in a higher number of patients who can omit surgery in favor of organ preservation and a surveillance protocol. Patients receive radiochemotherapy with 5-FU or capecitabine followed by standard consolidation chemotherapy with 5-FU/folinic acid/oxaliplatin or CAPOX. Hyperthermia will take place based on a 1:1 randomisation. After evaluation of treatment response in week 22 patients will either undergo surgical resection in case of residual tumor or non-operative management when a clinical complete response is seen or repeat evaluation after another 3 months in case of a near clinical complete response. In selected cases endoscopic procedures can be considered as an alternative to radical surgery.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 TME-free survival will be used (TMEFS).

Study Type

Interventional

Enrollment (Estimated)

264

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Germany
    • Baden-Württemberg
      • Tuebingen, Baden-Württemberg, Germany, 72076
      • Tübingen, Baden-Württemberg, Germany, 72076

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  • Major surgery within the last 4 weeks prior to inclusion
  • 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
  • Psychological, familial, sociological or geographical conditions potentially hampering compliance with the study protocol and follow-up schedule (these conditions should be discussed with the patient before registration in the trial)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Radiochemotherapy with hyperthermia followed by consolidation chemotherapy
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
Additional hyperthermia to radiochemotherapy regime in Arm 1 and radiochemotherapy without additional hyperthermia in Arm 2.
Radiation: Radiotherapy
Radiotherapy of the pelvis
Drug: Chemotherapy with 5-fluorouracil
Chemotherapy with 5-flurouracil is given in parallel to radiotherapy
Drug: Consolidation chemotherapy with FOLFOX
Consolidation chemotherapy with 5-fluorouracil and oxaliplatin
Active Comparator: Radiochemotherapy without hyperthermia followed by consolidation chemotherapy
Radiochemotherapy without hyperthermia followed by consolidation chemotherapy. After restaging decision to watch and wait in case of complete response or surgery
Radiation: Radiotherapy
Radiotherapy of the pelvis
Drug: Chemotherapy with 5-fluorouracil
Chemotherapy with 5-flurouracil is given in parallel to radiotherapy
Drug: Consolidation chemotherapy with FOLFOX
Consolidation chemotherapy with 5-fluorouracil and oxaliplatin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Two-year TME-free survival (TMEFS)
Time Frame: From September 2024 until September 2036
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital Tuebingen

Collaborators

Charite University, Berlin, Germany
University Hospital Erlangen

Investigators

  • Principal Investigator: Cihan Gani, MD, Prof. Dr., University Hospital Tuebingen

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 11, 2024

Primary Completion (Estimated)

June 1, 2036

Study Completion (Estimated)

March 1, 2037

Study Registration Dates

First Submitted

December 3, 2024

First Submitted That Met QC Criteria

February 12, 2025

First Posted (Actual)

March 25, 2025

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

February 12, 2025

Last Verified

November 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 182/2024BO1

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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