Phase I 'Run in' Study Followed by Randomised Phase II Trial Testing Intra-tumoural Hydrogen Peroxide as a Radiation Sensitizer in Women With Locally Advanced/Recurrent Breast Cancer in Terms of Toxicity and Tumour Response

PLEASE NOTE: Phase II of this protocol will now be conducted under protocol CCR5119/IRAS 264012 (NCT03946202)

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 women with poorly controlled symptoms.

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. The investigators want to test this approach, starting with a careful study of side effects in 12 patients (pilot study) followed by a randomised trial in 84 patients to test activity against cancer (Phase II). 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. Review of the Pilot study data by an independent committee of experts will be completed before starting the phase II (efficacy) study.

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.