A phase I/randomised phase II trial of abiraterone acetate with or without RO5503781 in patients with mCRCP who have not previously received docetaxel.

Phase 1

• Conditions: Cancer; MedDRA version: 18.1Level: PTClassification code 10060862Term: Prostate cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2013-002014-13-GB
• Lead Sponsor: HS greater Glasgow and Clyde

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2014-03-31
• Last Update Posted: 20 July 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Male
• Target Recruitment: 132

Inclusion Criteria

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 (eg. 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:
a.PSA progression. This must be based on a series of at least 3 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 (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 since commencing last systemic anti-cancer therapy as defined by RECIST 1.1 (Eisenhauer et al. 2009 Eur J Cancer. 4 5:2 2 8) for non-bone disease or the appearance of 2 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. ECOG PS = 0 or 1.
8. Hb>= 10g/dL; platelets >= 150 x 109/L; neutrophils >=1.5 x109/L.
9. Bilirubin < 1.5 x ULN; ALT and/ or 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 > 3 months.
14.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 32
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 100

Exclusion Criteria

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.
3. Uncontrolled hypertension (bp= 160 / 95 mmHg)
4. Significant heart disease as evident by MI or arterial thrombotic events in past six 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 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) (eg. Concomitant myelodysplastic syndrome)
11. Patients who refuse blood products.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified