KORTUC Phase II - Intra-tumoural Radiation Sensitizer in Patients With Locally Advanced/Recurrent Breast Cancer

March 1, 2024 updated by: Institute of Cancer Research, United Kingdom

Randomised Phase II Trial Testing Efficacy of Intra-tumoural Hydrogen Peroxide as a Radiation Sensitiser in Patients With Locally Advanced/Recurrent Breast Cancer

This is a study aimed at testing a commonly available and inexpensive chemical (hydrogen peroxide) for efficacy in sensitising large cancerous lumps in the breast to a standard course of radiotherapy in patients with locally advanced or recurrent breast cancer. Laboratory research and initial clinical trials in Japan suggest that 4 to 6 injections of a radiation sensitiser ('KORTUC') based on very dilute (0.5%) hydrogen peroxide injected into cancers under local anaesthetic twice a week during radiotherapy greatly increases the effectiveness of standard doses of radiotherapy alone. The side effects are limited to mild/moderate discomfort at the injection site for up to 24 hours reported by Japanese breast cancer patients in whom this treatment has been tested. Complete tumour shrinkage in 70/71 (98%) primary breast cancers up to 5 cm diameter have been reported by Japanese collaborators.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Aim: To test a slow release gel containing a commonly available and inexpensive chemical (hydrogen peroxide) for safety and activity in sensitizing large cancerous lumps in the breast or armpit to a standard 3-week course of radiotherapy in patients with locally advanced or recurrent breast cancer.

Background: Laboratory research and initial clinical trials conducted in Japan raises the possibility that a simple and inexpensive treatment based on a very dilute (0.5%) hydrogen peroxide injected into cancers under local anaesthetic greatly increases the effectiveness of standard doses of radiotherapy. The side effects appear to be limited to mild/moderate discomfort at the injection site for up to 24 hours in one-third of patients. Rapid, complete and durable tumour disappearance has been reported in 49/55 bulky breast cancers in Japanese women treated using this approach, a response that is at least 3 times the success rate of radiotherapy alone in our own patients and in a contemporary Japanese control population. The inventor, Prof Ogawa of Kochi University, has approached the investigators to lead the further clinical evaluation and commercial development, starting with the proposed early phase trials testing safety and anti-cancer activity described below.

Design and methods: After numbing the skin with local anaesthetic, a specialist doctor (radiologist) or trained radiographer will use ultrasound to guide the injection of a small volume of dilute (0.5%) hydrogen peroxide solution into the tumour twice a week during 3 weeks of standard radiotherapy. The drug is suspended in a natural gel (1% sodium hyaluronate, licensed for treating stiff knee joints) that ensures its slow release over 48 hours. The injection procedure lasts for 10-15 minutes altogether. Tiny oxygen bubbles are released from the hydrogen peroxide which help the radiologist guide the injection of drug to the proper places under the skin. We have recently completed a safety study confirming the mildness of side effects in 12 patients, and we now wish to test activity against cancer in a randomised controlled trial in 184 patients. Patients participating in Phase II will either have standard radiotherapy or the same radiotherapy plus the drug under test. Neither the patient nor the doctor will choose who has which treatment, which is allocated randomly.

Patient and public involvement: Independent Cancer Patient Voice, a patient advocate group in the field of cancer, is collaborating with the investigators on the research plan, commenting and advising on the content and clarity of the written proposal. This group plays a prominent role in promoting UK clinical research, being represented on the Trial Management Groups of several national randomised cancer clinical trials.

Dissemination: The results of this study will be presented at scientific meetings and at meetings of the patient advocate group in order to judge if the results for safety and activity are promising enough to justify taking the research further.

Study Type

Interventional

Enrollment (Estimated)

184

Phase

  • Phase 2

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

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

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patient age 18 years and over
  • Primary locally advanced breast cancer, or locally recurrent breast cancer with/without metastases (metastases, if present, should be stable or oligometastatic)
  • Radical/high dose palliative radiotherapy required for lifetime control of local morbidities
  • Patient physically and mentally fit for radical/high dose palliative radiotherapy
  • Target tumour accessible for intra-tumoural injection
  • Patient suitable/compliant with MR protocol
  • At least one tumour diameter ≥30 mm and ≤150 mm measurable by ultrasound or MR imaging
  • Patients with predicted life expectancy of 12 months or more
  • Negative pregnancy test before start of radiotherapy in women of child bearing potential and an ability/willingness to protect against pregnancy from consent and for 3 months post-radiotherapy
  • Patient offers written informed consent

Exclusion Criteria:

  • Prior radiotherapy to the target area
  • Maximum diameter of target tumour <30 mm or >150mm measurable by ultrasound or MR
  • Anatomical location and/or extent of disease difficult to access for safe intra-tumoural drug injections, for example by virtue of contiguous major blood vessels and/or brachial plexus
  • Concomitant chemotherapy or biological therapy except Herceptin, Pertuzumab and Denosumab (all endocrine therapies and bisphosphonates are allowed concomitantly; other cytotoxics and biological therapies apart from those mentioned above should be stopped 3 weeks prior to RT)
  • Pregnancy or nursing
  • Hypersensitivity to any of the KORTUC ingredients

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: Radiotherapy + radiation sensitiser
Patients randomised to the test group will receive standard radiotherapy for breast cancer + a radiation sensitiser
Drug: Hydrogen Peroxide
Hydrogen Peroxide
No Intervention: Radiotherapy alone
Patients randomised to the control group will receive standard radiotherapy for breast cancer alone

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Complete tumour response based on best response assessed by contrast enhanced MRI according to criteria outlined in Section 3.2.1 of the trial protocol, performed up to and including 12 months post radiotherapy
Time Frame: Up to and including 12 months post radiotherapy
Up to and including 12 months post radiotherapy

Secondary Outcome Measures

Outcome Measure
Time Frame
Proportion of patients withdrawing from study due to pain from intratumoural injections recorded at 2-week post-RT visit
Time Frame: During radiotherapy, an average of 3 weeks
During radiotherapy, an average of 3 weeks
Proportion of patients with partial response and stable disease
Time Frame: 12 and 24 months post radiotherapy
12 and 24 months post radiotherapy
Planned/unplanned tumour excision and pathological response recorded at post-RT follow-up visits
Time Frame: During 24-month follow up period
During 24-month follow up period
Overall survival at 6, 12 and 24 months
Time Frame: 6, 12 and 24 months post radiotherapy
6, 12 and 24 months post radiotherapy
Loco-regional progression-free survival and distant recurrence at 6, 12 and 24 months
Time Frame: 12 and 24 months post radiotherapy
12 and 24 months post radiotherapy
Proportion of patients with either complete response on MRI up to and including 12 months or pathological complete response following tumour resection before 12 months
Time Frame: Up to and including 12 months post radiotherapy
Up to and including 12 months post radiotherapy
Adverse events (assessed by NCI CTCAE v5.0)
Time Frame: Up to 90 days post radiotherapy
Up to 90 days post radiotherapy
Compliance with KORTUC injections prior to radiotherapy
Time Frame: During radiotherapy, an average of 3 weeks
During radiotherapy, an average of 3 weeks
Pain at target tumour site following KORTUC injections (10-point scale)
Time Frame: During radiotherapy, an average of 3 weeks
During radiotherapy, an average of 3 weeks
Patient-reported quality of life questionnaires (EORTC QLQ-C30 and BR23)
Time Frame: During 24-month follow up period
During 24-month follow up period
Resource use and health-related quality of life (EQ-5D-5L) for health economics analysis
Time Frame: During 24-month follow up period
During 24-month follow up period

Collaborators and Investigators

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

Sponsor

Institute of Cancer Research, United Kingdom

Collaborators

Kortuc, Inc.

Investigators

  • Principal Investigator: Navita Somaiah, The Institute of Cancer Research & The Royal Marsden NHS Foundation Trust

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)

June 16, 2020

Primary Completion (Estimated)

November 30, 2027

Study Completion (Estimated)

November 30, 2027

Study Registration Dates

First Submitted

May 8, 2019

First Submitted That Met QC Criteria

May 9, 2019

First Posted (Actual)

May 10, 2019

Study Record Updates

Last Update Posted (Estimated)

March 4, 2024

Last Update Submitted That Met QC Criteria

March 1, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CCR5119
  • 2019-001709-25 (EudraCT Number)

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

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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