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Phase II single-arm study evaluating abiraterone acetate (plus prednisolone) and Gonadotropin-Releasing Hormone (GnRH) agonist prior to receiving radical radiotherapy in high risk localised prostate carcinoma patients

Phase 1
Conditions
High-risk prostate cancer
MedDRA version: 20.0Level: 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
EUCTR2014-001128-31-IE
Lead Sponsor
Cancer Trials Ireland
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
ot Recruiting
Sex
Male
Target Recruitment
36
Inclusion Criteria

Each patient must meet all of the following inclusion criteria to be eligible for the study:

1. Provision of written informed consent prior to any study-related procedures

2. Male age = 18 years of age

3. Eastern Cooperative Oncology Group (ECOG) performance status =1 (See Appendix B of the study protocol)

4. Life expectancy = 10 years, as per clinician’s decision

Select Ireland - Scroll to ‘expectation of life at age x’ using the most recent indicator for Males)
5. Pathological proven prostate carcinoma at intermediate to high risk of recurrence as defined by RTOG:
• Gleason =8; or clinical stage =T3a; or PSA(#) =20 ng/ml(equivalent to AJCC 7th edition 2010 (Edge et al., 2010) / UICC group IIB and III)

• Or 2 or more of the following factors:
??Gleason = 7;
??PSA >10 ng/ml but =20 ng/ml,
??T2b-2c (equivalent to AJCC 7th edition 2010 (Edge et al. 2010) / UICC group II)

• And planned for radical radiotherapy (External Beam radiation therapy/ Brachytherapy / combination of both) and with an indication for neo-adjuvant hormonal therapy
[Note: (#): Study entry PSA must not be obtained during the following time frames:
(1) 10-day period following prostate biopsy;
(2) following initiation of ADT;
(3) within 30 days after discontinuation of finasteride;
or (4) within 90 days after discontinuation of dutasteride]

6. Clinically negative lymph nodes (N0) as established by imaging (pelvic CT / MRI), nodal sampling, or dissection within 90 days prior to registration, except patients with lymph nodes equivocal or questionable by imaging are eligible without biopsy if the nodes are =1.5 cm; any node larger than this on imaging will require negative biopsy for eligibility.

7. No evidence of bone metastases (M0) on bone scan within 90 days prior to registration. Equivocal bone scan findings are allowed if plain film x-rays are negative for metastasis.

8. Clinical laboratory values during screening:
• Haemoglobin = 10.0 g/dl
• Absolute neutrophil count (ANC) = 1.8 × 109/L
• Platelets = 100 × 109/L
[Note: Study patients need to meet the above 3 criteria independent of growth factors and transfusions]
• Total bilirubin = 1.5× upper limit of normal (ULN)
• Alanine (ALT) and aspartate (AST) aminotransferase = 2.5 × ULN
• Alkaline Phosphatase (ALP) = 6 × ULN
• Serum creatinine =1.5 × ULN or creatinine clearance =50 mL/min (Calculated GFR using Cockcroft and Gault Formula) (see Appendix C of the study protocol)
• Serum potassium =3.5 mM
• Serum albumin =3.0 g/dL
• Clinically normal prothrombin (PT) or international normalised ratio (INR) per Investigator assessment

9. Systolic blood pressure <160 mmHg and diastolic blood pressure <95 mmHg
[Note: medically controlled hypertension is permitted]

10. Prostate gland size measurable by TRUS and at least =30 cm3 at baseline (in accordance with Ferring CS 30 study - NCT00833248)

11. Patient is willing to use barrier-method contraception, e.g. a condom, along with another effective contraceptive method if engaged in sexual activity with a pregnant woman or a woman of child-bearing potential (until 1 week after completing treatment)

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 9
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 27

Exclusion Criteria

Each patient must meet none of the following exclusion criteria to be eligible for the study:

1. Prior treatment for prostate carcinoma, including prostatectomy; high-intensity focused ultrasound or cryotherapy; hormonal manipulation (any modalities) including LHRH agonist, anti-androgen, or bilateral orchidectomy; prior or concomitant chemotherapy for prostate cancer; prior radiotherapy including brachytherapy to the region of study cancer; radical local treatment [Exception: TURP / TRUS is allowed]

2. Use of urethral catheter (in accordance with Ferring CS 30 study - NCT00833248)

3. History of cardiovascular disease; Uncontrolled hypertension [hypertension controlled by anti-hypertensive therapy is permitted], clinically significant heart disease as evidenced by myocardial infarction, or arterial thrombotic events in the past 6 months, severe or unstable angina, or NYHA Class III or IV heart failure (See Appendix E of the study protocol), or Class II to IV heart failure of cardiac ejection fraction measurement of <50% [cardiac ejection fraction measured by MUGA or ECHO - if indicated, at Investigator’s discretion]

4. Active or symptomatic viral hepatitis, chronic liver disease or severe hepatic impairment

5. Major thoracic or abdominal surgery or significant traumatic injury within 4 weeks prior to registration, or planned surgery during study participation / within 4 weeks from end of treatment [Note: patients with planned surgical procedure to be conducted under local anaesthesia are not excluded from the study]

6. Gastrointestinal disorder interfering with study drug absorption

7. Active or uncontrolled disease that may require oral corticosteroid therapy

8. Positive serology for hepatitis B surface antigen or hepatitis C antibody

9. Known allergies, hypersensitivity or intolerance to abiraterone acetate, prednisolone, GnRH agonists or their excipients

10. Contraindications to the use of prednisolone or GnRH agonists per local prescribing information

11. Evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the patient to participate in the study

12. Any condition that, in the opinion of the investigator, would compromise the well-being of the patient or that could prevent, limit, or confound the protocol-specified assessments

13. The patient has or had other co-existing malignancies within the past 5 years, other than resected non-melanoma skin cancer

14. Treatment with non-approved or investigational drug within 30 days before the first planned dose of study drug

15. Treatment with any prohibited medication (as outlined per protocol section 7.4.1) which cannot be discontinued.

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Secondary Outcome Measures
NameTimeMethod
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