Prostate Adenocarcinoma: TransCutaneous Hormones versus luteinising hormone-releasing hormone (LHRH) analogues

Phase 3

Conditions: Prostate cancer
Cancer
Malignant neoplasm of prostate

Registration Number: ISRCTN70406718

Lead Sponsor: Imperial College London (UK)

Brief Summary: 2008 Other publications in http://www.ncbi.nlm.nih.gov/pubmed/18422771 Early hormonal data 2013 Other publications in http://www.ncbi.nlm.nih.gov/pubmed/23465742 Cardiovascular outcomes 2016 Other publications in https://www.ncbi.nlm.nih.gov/pubmed/26707868 1-yr change in lumbar spine bone mineral density in a subset of participants 2021 Other publications in https://pubmed.ncbi.nlm.nih.gov/33581820/ Long-term cardiovascular mortality and morbidity (added 15/02/2021)

Detailed Description: Not available

Recruitment & Eligibility

Status: Ongoing

Sex: Male

Target Recruitment: 1854

Inclusion Criteria

Current inclusion criteria as of 09/12/2014:
Newly diagnosed patients with one of the following:
1. Stage T3/4 NO or NX M0 histologically confirmed prostate adenocarcinoma with PSA =20 ng/ml or Gleason sum score =6
2. Stage Tany N+ M0 or Tany Nany M+ histologically confirmed prostate adenocarcinoma
3. Multiple sclerotic bone metastases with a PSA =50 ng/ml without histological confirmation of prostate cancer
OR
Patients with histologically confirmed prostate adenocarcinoma previously treated with radical surgery and/or radiotherapy who are now relapsing, with at least one of the following:
1. PSA =4 ng/ml and rising with doubling time less than 6 months
2. PSA =20 ng/ml
3. Documented evidence of metastatic disease with PSA >4 ng/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 4 weeks prior to date of randomisation) are eligible. Patients who have started cyproterone acetate prior to randomisation are not eligible.

AND
For all patients
1. Intention to treat with continuous long-term ADT (> 3 years)
2. Fit for all protocol treatment and follow-up, WHO performance status 0-2
3. Should have completed the appropriate investigations prior to randomisation
4. Normal testosterone level prior to hormone treatment (>6 nmol/L)
5. Written informed consent
6. Willing and expected to comply with follow-up schedule
7. For newly diagnosed N0M0 patients only - Intention to treat with radical radiotherapy

Previous inclusion criteria:
Newly diagnosed patients with one of the following:
1. Stage T3/4 NX M0 histologically confirmed prostate adenocarcinoma with prostate specific antigen (PSA) greater than or equal to 20 ng/ml or Gleason sum score greater than or equal to 6
2. Stage Tany N+ M0 or Tany Nany M+ histologically confirmed prostate adenocarcinoma
3. Multiple sclerotic bone metastases with a PSA greater than or equal to 50 ng/ml without histological confirmation

Patients with histologically confirmed prostate adenocarcinoma previously treated with radical surgery or radiotherapy who are now relapsing with one of:
1. PSA greater than or equal to 4 ng/ml and rising with doubling time less than 6 months
2. PSA greater than or equal to 20 ng/ml

For all patients:
1. Intention to treat with long-term androgen deprivation therapy (ADT)
2. Fit for all protocol treatment and follow-up, World Health Organization (WHO) performance status 0 - 2
3. Have completed the appropriate investigations prior to randomisation
4. Normal testosterone level prior to hormone treatment
5. Written informed consent
6. Willing and expected to comply with follow-up schedule

Exclusion Criteria

Current exclusion criteria as of 09/12/2014:
1. Prior systemic therapy for locally advanced or metastatic prostate cancer except as listed in participant inclusion criteria
2. Any other previous or current malignant disease or CVS disease which is thought likely to compromise the patient’s ability to tolerate therapy or affect assessment
3. Cardiovascular exclusions:
3.1. Any history of cerebral ischaemia (e.g. stroke or TIA) within 2 years of randomisation
3.2. Any history of DVT or PE confirmed radiologically or a known thrombophilic disorder (e.g. Protein C, protein S, or antithrombin deficiency)
3.3. History of myocardial infarction/acute coronary syndrome:
3.3.1. Within the last 6 months
3.3.2. Greater than 6 months with evidence of q-wave anterior infarct on ECG
3.4. Unstable angina (typical cardiac chest pain at rest lasting more than 15 minutes) within the last year
3.5. 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
3.6. Heart failure: if patients have symptoms such as shortness of breath or oedema that are attributable 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
3.7. BP =160/100 (if either systolic or diastolic BP is greater than or equal to these values then the patient is not eligible)
3.8. Pulmonary oedema on CXR
4. Known porphyria

Previous exclusion criteria:
1. Prior systemic therapy for locally advanced or metastatic prostate cancer
2. Any other previous or current malignant disease or CVS disease which, in the judgement of the responsible physician, is likely to interfere with PATCH treatment or assessment.
3. Cardiovascular exclusions:
3.1. Any history of cerebral ischaemia (e.g. stroke or transient ischaemic attack [TIA])
3.2. Any history of deep vein thrombosis (DVT) or pulmonary embolism (PE) confirmed radiologically
3.3. History of myocardial infarction
3.3.1. Within the last 6 months
3.3.2. Greater than 6 months with evidence of q-wave anterior infarct on electrocardiogram (ECG) (right lead [RL])
3.4. Unstable angina (typical cardiac chest pain at rest lasting more than 15 minutes) within the last year
3.5. 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
3.6. 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
3.7. Blood pressure (BP) greater than or equal to 160/100 (if either systolic or diastolic BP greater than these values then the patient is not eligible)
3.8. Pulmonary oedema on chest x-ray (CXR)

Patients that have a history of ischaemic heart disease or heart failure are required to have an Echocardiogram (ECHO) or multiple-gated acquisition scan (MUGA). Patients with left ventricular ejection fraction less than 40% will be excluded.