E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Metastatic, castration-resistant prostate cancer |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10036909 |
E.1.2 | Term | Prostate cancer metastatic |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 |
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). |
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E.2.2 | Secondary objectives of the trial |
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. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 (<1.7nmol/l). 4. Male aged 18 or over. 5. ECOG PS = 0 or 1. 6. Hb >= 10g/dL; platelets >= 100 x 109/L; neutrophils >=1.5 x109/L. 7. Bilirubin <= ULN; ALT, AST <= 1.5 x ULN. 8. Serum Creatinine <=1.5 x ULN or calculated creatinine clearance >= 50 ml/min 9. Able to swallow study drugs. 10. Life expectancy > 3 months. 11. Provision of written informed consent.
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E.4 | Principal 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.
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E.5 End points |
E.5.1 | Primary end point(s) |
Phase I: Safety and tolerability. Phase II: Progression free survival. |
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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 | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
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) | Yes |
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) | 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 | Yes |
E.8.1.5 | Parallel group | Yes |
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 | Yes |
E.8.2.3 | Other | No |
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 | 12 |
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 | 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
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For the purposes of Clinical Trial Authorisation, the trial is deemed to have ended 30 days after the last patient remaining on treatment receives the last dose of saracatinib or placebo |
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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 | 3 |
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 | 3 |
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 |