MAdCaP: MDM2 inhibition and Abiraterone in Carcinoma of the Prostate
- Conditions
- Prostate cancerCancerMalignant neoplasm of prostate
- Registration Number
- ISRCTN38949950
- Lead Sponsor
- HS Greater Glasgow and Clyde (UK)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Male
- Target Recruitment
- 132
1. Histologically proven adenocarcinoma of the prostate with documented metastases (where the metastatic lesions are confined to 1 or 2 lesions on a bone scan. These must be confirmed by a second modality (e.g. CT, MRI or biopsy).
2. Availability of archival tumour samples. Where patients are willing to undergo a biopsy as part of the study, these specimens may be used as an alternative where no archival specimen is available.
3. Proven disease progression since last change in therapy defined by at least one of the following:
3.1. Prostate-specific antigen (PSA) progression. This must be based on a series of at least three successively increasing readings each taken at least 7 days apart. The 3rd reading must be >= 2ng/ml. In the event where an intermediate reading is lower than a previous reading, then the patient will still be eligible (i.e. the three readings do not need to be consecutive). The first of the three readings must have been obtained after commencing the previous systemic therapy, or, in the case of androgen receptor antagonists, after discontinuing.
3.2. Radiographic progression since commencing last systemic anti-cancer therapy as defined by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 (Eisenhauer et al. 2009 Eur J Cancer. 4 5:2 2 8) for non-bone disease or the appearance of two or more new lesions on a bone scan.
4. Castrate levels of serum testosterone (<1.7nmol/l)
5. On-going castration therapy
6. Male aged 18 or over
7. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) = 0 or 1
8. Haemoglobin (Hb)>= 10g/dL; platelets >= 150 x 109/L; neutrophils >=1.5 x109/L
9. Bilirubin < 1.5 x ULN; alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) < 2.5 x ULN
10. Serum potassium = LLN; Alb = 30 g/L
11. Serum creatinine < 1.5 x ULN or a calculated creatinine clearance = 60 mL/min
12. Able to swallow study drugs
13. Life expectancy of more than 3 months
14. Provision of written informed consent
1. Prior cytotoxic chemotherapy for castration resistant prostate cancer (patients may have received previous or ongoing bisphosphonates, eg. zoledronate, or denosumab)
2. Prior ketoconazole, abiraterone, MDV3100 (enzalutamide), TAK-700 (orteronel) or other novel anti-hormonal therapies
3. Uncontrolled hypertension ( BP= 160 / 95 mmHg)
4. Significant heart disease as evident by myocardial infarction (MI) or arterial thrombotic events in past 6 months, severe unstable angina, or New York Heart Association class (NYHA) III or IV heart failure or class II to IV heart failure or cardic ejection fraction measurement of <50%.
5. Other anticancer therapy [apart from Luteinizing-hormone-releasing hormone (LHRH) agonist / antagonist] within 4 weeks (6 weeks for bicalutamide). This includes radiotherapy and therapeutic radionucleotides. Where patients are receiving bisphosphonates or denosumab they must have been on a stable dose for at least 6 weeks prior to starting study drug.
6. The requirement for strong opiates to control cancer related pain in the two weeks before study entry (codeine and tramadol are permitted)
7. Patient with a partner of child-bearing potential who is not using a highly effective method of contraception, who is unwilling to use condoms during the study and for 30 days after the last dose of study drug
8. Patients with known coagulopathy, platelet disorder or history of non-drug induced thrombocytopenia
9. Patients receiving oral or parenteral anti-coagulants/anti-platelet agents (chronic daily treatment with aspirin with doses >325 mg po daily, clopidogrel, low molecular weight heparin, or dagibatran, etc.) prior to the start of study therapy are excluded. Patients may receive anticoagulant flushes for maintenance of indwelling catheters.
10. Patients with known bone marrow disorders which may interfere with bone marrow recovery (due to tumor involvement, fibrosis) (e.g. Concomitant myelodysplastic syndrome)
11. Patients who refuse blood products
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <br> Radiological progression free survival [as per Prostate Cancer Working Group (2) (PCWG2)]<br> Patients will have CT and bone scans at baseline then every 8 weeks for the first 24 weeks, thereafter every 12 weeks until progression is confirmed. Progression-free survival will be measured from the date of randomisation to the date of progression or date of death (any cause) for those who do not progress.<br>
- Secondary Outcome Measures
Name Time Method