| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Newly diagnosed or relapsing patients with locally advanced or metastatic prostate cancer |
|
| E.1.1.1 | Medical condition in easily understood language |
| Newly diagnosed or relapsing patients with locally advanced or metastatic prostate cancer |
|
| 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 |
The PATCH trial is a randomised study evaluating a novel approach (transdermal oestrogens) for the treatment of locally advanced and metastatic prostate cancer.
The primary objective of the trial is to confirm that transdermal oestrogen is a safe and efficacious therapy for patients with locally advanced and metastatic prostate cancer. The final phase III evaluation of efficacy will test the hypothesis that patches are non-inferior to standard androgen deprivation therapy in terms of overall survival and progression-free survival.
|
|
| E.2.2 | Secondary objectives of the trial |
| The secondary outcome measures are metastasis-free prostate cancer-specific survival (for M0 patients only), cardiovascular morbidity and mortality, cardiovascular risk factors (including glucose and lipids), hormone levels (oestrogen, testosterone, PSA), toxicity, and quality of life. |
|
| 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 |
- ABIRATERONE SUB STUDY - detailed in Appendix O of the PATCH protocol v11.0, February 2019.
The aim of the Abiraterone sub-study is to understand the efficacy and toxicity of the combination of transdermal oestradiol and abiraterone acetate in the treatment of men with prostate cancer.
- PROGYNOVA SUB STUDY - detailed in Appendix O of the PATCH protocol v10.0, August 2015.
This aims to confirm the appropriate dose of Progynova TS 100 patches for achieving castrate levels of testosterone in previously hormone-naïve patients, with approximately 70 patients to be randomised in a 1:2 ratio of LHRH:Progynova.
The primary outcome measure is the proportion of men with castrate levels of testosterone at 12 weeks. Secondary outcomes include: castration rates at 4 weeks and 6 months; oestradiol and PSA levels up to 6 months; and early cardiovascular and other toxicity. The eligibility criteria will be the same as that for the main trial.
- BONE (DXA) SUB-STUDY - detailed in Appendix K of the PATCH protocol v9.0, March 2014.
The aim of the DXA sub-study is to compare bone mineral density (BMD) in patients receiving transcutaneous oestrogen patches with those receiving LHRH analogues and to quantify the annual changes in BMD between the transcutaneous oestrogen patches and LHRH analogue groups during the study period. Recruitment to the sub-study is complete and results were presented at ASCO 2014 showing that patients on oestrogen patches had preserved bone mineral density at one year and two years post-randomisation compared to patients on LHRH agonists.
- QUALITY OF LIFE SUB-STUDY - detailed in SECTION 10 of the PATCH protocol version 10.0, August 2015.
A quality of life (QL) study is being performed to assess the impact of each treatment arm on the quality of patients’ lives. All patients should be asked if they are willing to participate. The general EORTC QLQ-C30 with the prostate-specific module QLQ PR25, with a few additional questions will be used and measured up to 2 years post-randomisation. Key items for assessment are pain reduction for patients with metastatic disease and urinary symptoms for patients with locally advanced disease.
|
|
| E.3 | Principal inclusion criteria |
Newly Diagnosed Patients
with at least one of:
(i)Stage T3/4 NO or NX M0 histologically confirmed prostate adenocarcinoma with either PSA≥20ng/ml or Gleason sum score ≥6
(ii)Stage Tany N+ M0 or Tany Nany M+ histologically confirmed prostate adenocarcinoma
(iii)Multiple sclerotic bone metastases with a PSA≥50ng/ml without histological confirmation of prostate cancer
OR
Patients with histologically confirmed prostate adenocarcinomapreviously treated with radical surgery and/or radiotherapy who are now relapsing
with at least one of:
(i)PSA ≥4ng/ml and rising with doubling time less than 6 months
(ii)PSA ≥20ng/ml
(iii)Documented evidence of metastatic disease with PSA>4ng/ml
Note: Prior hormone therapy for localised disease must have been completed at least 12 months previously and have been no longer than 12 months in duration. It can have been given as adjuvant or neoadjuvant therapy.
Patients who have started Bicalutamide or Flutamide (up to 8 weeks prior to date of randomisation) are eligible. Patients who have started Cyproterone Acetate prior to randomisation are not eligible.
AND
For all patients:
(i)Intention to treat with long-term androgen deprivation therapy (> 3 years).
(ii)Fit for all protocol treatment and follow-up, WHO performance status 0-2 (see protocol v12.0 Appendix A)
(iii)Should have completed the appropriate investigations prior to randomisation (see protocol v12.0 section 4.4)
(iv)Written informed consent
(v)Willing and expected to comply with protocol
(vi)For newly diagnosed N0M0 patients only - Intention to treat with radical radiotherapy (unless there is a specific contraindication; exemption can be sought in advance of consent after discussion with the PATCH Trial Manager). |
|
| E.4 | Principal exclusion criteria |
(i)Prior systemic therapy for locally advanced or metastatic prostate cancer except as listed in protocol section 4.2.
(ii)Any other previous or current malignant disease or Cardiovascular disease which is thought likely to compromise the patient’s ability to tolerate therapy or affect assessment.
(iii) Cardiovascular exclusions:
a. Any history of cerebral ischaemia (e.g. Stroke or TIA) within 2 years of randomisation
b. Any history of deep vein thrombosis or pulmonary embolism confirmed radiologically or a known thrombophilic disorder
(e.g. Protein C, protein S, or antithrombin deficiency)
c. History of myocardial infarction/acute coronary syndrome
(i)within the last 6 months
(ii)greater than 6 months with evidence of q-wave anterior infarct on ECG*1 and 2
d. Unstable angina (typical cardiac chest pain at rest lasting more than 15 minutes) within the last year *2.
e. Angina that occurs on walking 100 metres on the level or after climbing one flight of stairs at a normal pace and in normal condition, or angina that causes marked limitation of ordinary physical activity or occurs at rest*2.
f. Heart failure: If patients have symptoms such as shortness of breath or oedema that are attributed to heart failure and this causes marked limitation of activity and/or they are comfortable only at rest then they should be excluded from the study*2.
g. Pulmonary oedema on CXR.
(iv) Known porphyria.
*1 If assistance with interpretation of ECG is required and not available locally please fax ECG to PATCH Trial Manager on 020 7670 4818. Please allow two working days for a response. Any other cardiac queries can also be forwarded to the PATCH Trial Manager by telephone or email (and will be directed to the PATCH Trial Cardiologist).
*2 Patients that have a history of ischaemic heart disease or heart failure are required to have an ECHO or MUGA prior to randomisation. Patients with left ventricular ejection fraction ≤40% will be excluded from participating in the trial. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Primary outcomes:
- Overall survival
- Progression Free Survival
|
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| The co-primary outcomes, overall survival and progression free survival, will be evaluated at the final phase III efficacy analyses. The final phase III efficacy analysis will be performed when around 565 deaths and 815 progression free survival events have been observed in the control arm. |
|
| E.5.2 | Secondary end point(s) |
Secondary outcomes:
- Metastasis-free prostate cancer-specific survival (for M0 patients only)
- Cardiovascular morbidity and mortality
- Cardiovascular risk factors (including glucose and lipids)
- Hormone levels (oestradiol, testosterone, PSA)
- Toxicity (specifically osteoporosis, hot flushes, gynaecomastia, anaemia)
- Quality of life |
|
| 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 | Yes |
| 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 | Yes |
| 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 | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| 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 | Yes |
| 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) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| 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 | 50 |
| 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 | Information not present in EudraCT |
| E.8.7 | Trial has a data monitoring committee | Yes |
| 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
|
| Once follow-up is sufficient for the analysis of the primary outcome to be performed, the Trial Management Group will consider whether continued follow-up as per the trial schedule is still required, or if transition to a long term follow-up stage would be appropriate. (for more details please refer to protocol section 7.7). |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 16 |
| E.8.9.1 | In the Member State concerned months | |
| E.8.9.1 | In the Member State concerned days | |
Print
