E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with locally advanced/recurrent breast cancer |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Primary Objective: To test efficacy
Primary Endpoint: Complete tumour response 12 months post-radiotherapy assessed by MR according to criteria outlined below and in Section 3.4 of the trial protocol
MRI criteria for tumour response Complete response: No evidence of enhancement or tumour mass on MRI scan Partial response: Reduced tumour size but with residual mass and/or enhancement Stable disease: Stable tumour size and enhancement Progressive disease: Increased tumour size >20% and/or enhancement; New foci of tumour; Locoregional tumour spread
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E.2.2 | Secondary objectives of the trial |
Secondary Objective: To further characterise efficacy and safety
Secondary Endpoints: • Proportion of patients withdrawing from study due to pain from intratumoural injections • Patients achieving pathological complete response following tumour resection prior to the 12-month MR assessment • Proportion of patients with partial response and stable disease • Planned/unplanned tumour excision and pathological response • Loco-regional recurrence, local progression-free survival and distant recurrence at 6, 12 and 24 months (clinical radiological assessment) • Overall survival at 6, 12 and 24 months |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
1. Tumour biopsy and blood sampling sub-study 2. MRI sub-study 3. 3D super-resolution US sub-study
Exploratory Objectives: Test for novel mechanisms of action of radiation sensitiser and biomarkers of response
Exploratory endpoints: • Cell death and immune response markers before and after radiotherapy plus/minus drug, in blood and formalin-fixed paraffin embedded tumour tissue • Monitoring circulating tumor markers (e.g. circulating tumor DNA pre- and post-therapy) in blood • Early predictive biomarkers of response on DCE and DW-MRI pre- and post-RT plus/minus drug • Monitoring of abscopal responses in non-target lesions on routine imaging • Application of novel 3D super-resolution ultrasound (SRUS) imaging for radiotherapy response assessment in breast tumours (Subset of patients at RM, n=20) |
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E.3 | Principal inclusion criteria |
• Patient age 18 years and over • Primary locally advanced breast cancer, or locally recurrent breast cancer with/without metastases • 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 for 3 months post-radiotherapy • Patient offers written informed consent |
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E.4 | Principal exclusion criteria |
• Prior radiotherapy to the target area • Maximum diameter of target tumour <30 mm or >150mm measurable by ultrasound or MRI • 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 |
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E.5 End points |
E.5.1 | Primary end point(s) |
Complete tumour response 12 months post-radiotherapy assessed by MRI according to criteria outlined in section 3.4 of the trial protocol and below
MRI criteria for tumour response Complete response: No evidence of enhancement or tumour mass on MRI scan Partial response: Reduced tumour size but with residual mass and/or enhancement Stable disease: Stable tumour size and enhancement Progressive disease: Increased tumour size >20% and/or enhancement; New foci of tumour; Locoregional tumour spread |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
• Proportion of patients withdrawing from study due to pain from intratumoural injections recorded at 2-week post-RT visit • Patients achieving pathological complete response following tumour resection prior to the 12-month MR assessment will be included in a sensitivity analysis of the primary endpoint. • Proportion of patients with partial response and stable disease • Planned/unplanned tumour excision and pathological response recorded at post-RT follow-up visits • Loco-regional recurrence, local progression-free survival and distant recurrence at 6, 12 and 24 months (clinical and radiological assessment) • Overall survival at 6, 12 and 24 months
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description |
Phase I "run in" study to confirm findings by collaborators in Japan in 12 UK patients. |
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E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Radiotherapy without drug |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |