Metastatic, castration-resistant prostate cancer MedDRA version: 17.0 Level: PT Classification code 10036909 Term: Prostate cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: saracatinib
Product Code: AZD0530
Pharmaceutical Form: Tablet
Pharmaceutical form of the placebo: Tablet
Route of administ
Sponsors
NHS Greater Glasgow Health Board
Glasgow University
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1. Histologically or cytologically proven adenocarcinoma of the prostate with previously documented metastases. 2. Proven disease progression since last change in therapy defined by at least one of the following: a. PSA progression as defined by the prostate cancer working group (2) (PCWG2) criteria (Scher et al. 2008 J Clin Oncol. 26; 1148). This must be based on a series of at least 3 readings 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 (ie. the 3 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. b. Radiographic progression as defined by RECIST 1.1 (Eisenhauer et al. 2009 Eur J Cancer. 4 5:2 2 8) for non-bone disease. a. The appearance of 2 or more new lesions on a bone scan. 3. Castrate levels of serum testosterone (= 10g/dL; platelets >= 100 x 109/L; neutrophils >=1.5 x109/L. 7. Bilirubin = 50 ml/min 9. Able to swallow study drugs. 10. Life expectancy > 3 months. 11. Provision of written informed consent. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 45 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 105
Exclusion criteria
Exclusion criteria: 1. Prior cytotoxic chemotherapy for prostate cancer (patients may have received previous or ongoing bisphosphonates, eg. zoledronate). 2. Prior intolerance of cremaphor. 3. Other prior malignancy with estimated >= 30% chance of relapse within 2 years. 4. Previously identified brain metastases or spinal cord compression unless treated with full functional recovery. 5. Prior radionuclide therapy for prostate cancer. 6. Prior radiotherapy to > 30% of bone marrow. 7. Administration of investigational agent within 30 days of first dose of study medication. 8. Androgen receptor antagonist therapy during 6 weeks prior to initiation of study medication. 9. Any evidence of severe or uncontrolled systemic conditions (eg. Severe hepatic impairment, interstitial lung disease [bilateral, diffuse, parenchymal lung disease]) or current unstable or uncompensated respiratory or cardiac conditions which make it undesirable for the patient to participate in the study or which could jeopardise compliance with the protocol. 10. Resting ECG with measurable QTc interval of >480 msec at 2 or more time points within a 24 hour period. 11. Patients with known immunodeficiency syndrome. 12. Unable to discontinue any medication or herbal supplement that may significantly modulate CYP3A4 activity or which is significantly metabolised by CYP3A4. Such drugs must have been discontinued for an appropriate period prior to starting AZD0530. Guidance on medicines to avoid and on washout periods is given in Appendix to this protocol. 13. Unresolved toxicity = CTC grade 2 (except alopecia) from previous anti-cancer therapy. 14. Patients with a partner of child-bearing potential who is not using a highly effective method of contraception, who are unwilling to condoms during the study and for 30 days after the last dose of study drug. 15. Known hypersensitivity to AZD0530 (saracatinib), its excipients, or drugs in its class. 16. Known malabsorption syndrome.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): Phase I: Safety and tolerability. Phase II: Progression free survival. ; Main Objective: For the first part of the study (phase I), the primary objective is to find a safe and tolerable dose for saracatinib (AZD0530) given in combination with standard chemotherapy treatment (docetaxel and prednisolone) for patients with metastic castrate-refractory prostate cancer. For the second part of the study (phase II), the primary objective is to investigate whether we can improve the benefits of chemotherapy cancer treatment for patients with metastic castrate-refractory prostate cancer by adding a new drug, saracatinib (AZD0530). ; Secondary Objective: For the first part of the study (phase I), the secondary objective is to investigate the effects of saracatinib on how the body eliminates the docetaxel chemotherapy. For the second part of the study (phase II), the secondary objective is to estimate the effect of saracatinib on bone pain in patients with metastatic castrate-refractory prostate cancer. | — |
Countries
United Kingdom
Outcome results
None listed