Study of Dose Escalation of Abiraterone Actetate in Prostate Cancer

NCT03458247 | Completed Phase 2 DMC

• 2 other identifiers: P161201J2017-000560-15
• Study Type: interventional
• Target: 94
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to test whether a dose escalation up to 2000 mg per day of abiraterone acetate is feasible and lead to disease stabilization in castration-resistant metastatic prostate cancer patients who experience disease progression within the first 6 months of abiraterone actetate at standard dose (1000 mg/d) and have a plasma abiraterone concentration below 8.5 ng/mL. It is a non-comparative phase 2 study in which patients will be included in two successive steps. Patients with mCRPC will be included in the first step and treated with standard dose (1000 mg/day) of ABI + prednisone /prednisolone (10 mg/d) according to the summary of product characteristics and monitored for trough ABI plasma level each month for 3 months. In the second step intrapatient ABI dose escalation (2000 mg/day) + prednisone/prednisolone (10 mg/d) will be realized for patients from the first step experiencing progressive disease within 6 months of ABI standard dose and with mean ABI plasma level during the first three months \< 8.5 ng/mL

Conditions

Prostate Cancer

Keywords

Prostate Cancer; Castration resistance; Drug monitoring; Abiraterone acetate

Outcome Measures

Primary Outcomes (1)

• Non-progression rate

  The proportion of patients who do not experience progressive disease (defined by PSA and/or radiographic progression) among those receiving ABI at a dose of 2000 mg / day + prednisone/prednisolone after failure of standard dose (1000 mg/day).

  12 weeks

Secondary Outcomes (6)

• Incidence of underexposure to ABI

  3 months

• Evaluation of adherence to ABI and correlation with mean plasma ABI concentration

  3 months

• Evaluation of adherence to ABI and correlation with mean plasma ABI concentration

  6 months

• PSA response rate in patients treated at escalated dose

  6 months

• Progression free survival in patients treated at escalated dose

  6 months

Study Arms (2)

Abiraterone acetate standard dose

ACTIVE COMPARATOR

1000 mg/day

Drug: Abiraterone acetate standard dose

Abiraterone acetate escalated dose

EXPERIMENTAL

2000 mg/day

Drug: Abiraterone acetate escalated dose

Interventions

Abiraterone acetate standard dose DRUG

1000 mg/day

Abiraterone acetate standard dose

Abiraterone acetate escalated dose DRUG

2000 mg/day

Abiraterone acetate escalated dose

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Step 1
• Male 18 years and older.
• Voluntary signed informed consents of the patient before any study-specific procedure.
• Histologically confirmed prostate adenocarcinoma.
• Presence of bone and/or soft-tissue and/or visceral metastases through CT scan, MRI, scintigraphy scan.
• Progressive disease assessed by PSA, CT scan, MRI or bone scan according to the PCGW3 criteria PSA progression is defined as a 25% or greater increase and an absolute increase of 2 ng/mL or more from the nadir, which is confirmed by a second value obtained 1 or more weeks later. Bone scan: at least two or more new lesions are seen on bone scan compared with a prior scan.
• Patient with no or moderate symptoms (no need for continuous opioid treatment)
• Effective castration confirmed by testosterone plasma level \< 50 ng/dL
• ECOG performance status: 0-2
• Life expectancy \> 3 months
• Patient affiliate to french social assurance
• SGPT and SGOT \< 5 fold the upper normal value
• Kaliemia \> 3 mM
• Patient using an effective contraceptive method during treatment
• Step2

You may not qualify if:

• Step 1
• Pure small cell carcinoma of the prostate or predominant histology of neuro-endocrine carcinoma.
• Confirmed brain and/or leptomeningeal metastases
• Previous treatment with docetaxel or any other anticancer treatment for castration-resistant prostate carcinoma (previous docetaxel for hormone-sensitive metastatic disease is allowed)
• Previous treatment with ABI or any other 17 B hydroxylase inhibitor or enzalutamide
• Treatment with first-generation antiandrogen (ciproterone acetate, bicalutamide, flutamide, nilutamide) performed on the day of baseline or within previous four weeks, due to possible anti-androgen withdrawal response. (This criterion does not apply for subjects, who have never responded to anti-androgen treatment).
• Patient co-morbidities:
• Patients with the following hereditary diseases: galactose hypersensitivity, Lapp lactase deficiency.
• Cirrhosis Child-Pugh B or C
• Active or symptomatic viral hepatitis
• Heart failure stage NYHA III or IV
• Cardiac arythmia, heart failure stage NYHA II, ischemic cardiopathy or uncontroled hypertension, except if left ventricular ejection fraction is \> 50%
• Patients with left ventricular ejection fraction (LVEF) \< 50%
• Evidence of any other disease, metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or puts the patient at high risk for treatment related complications.Prior or concurrent malignant disease in complete remission for less than 3 years, except T1N0 vocal cord carcinoma, basal or squamous cell skin carcinoma and in situ transitional cell bladder carcinoma
• Limitation of the patient's ability to comply with the treatment or to follow-up the protocol.

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• Janssen, LP: collaborator
• URC-CIC Paris Descartes Necker Cochin: collaborator

Study Sites (1)

Department of Medical Oncology, Cochin Hospital

Paris, paris, 75014, France

Location

Related Publications (2)

• Alexandre J, Oudard S, Golmard L, Campedel L, Mseddi M, Ladoire S, Khalil A, Maillet D, Tournigand C, Pasquiers B, Goirand F, Berthier J, Guitton J, Dariane C, Joly F, Xylinas E, Golmard JL, Abdoul H, Puszkiel A, Decleves X, Carton E, Thomas A, Vidal M, Huillard O, Blanchet B. Intra-individual Dose Escalation of Abiraterone According to Its Plasma Exposure in Patients with Progressive Metastatic Castration-Resistant Prostate Cancer: Results of the OPTIMABI Trial. Clin Pharmacokinet. 2024 Jul;63(7):1025-1036. doi: 10.1007/s40262-024-01396-x. Epub 2024 Jul 4.

  PMID: 38963459 BACKGROUND

• Carton E, Noe G, Huillard O, Golmard L, Giroux J, Cessot A, Saidu NE, Peyromaure M, Zerbib M, Narjoz C, Guibourdenche J, Thomas A, Vidal M, Goldwasser F, Blanchet B, Alexandre J. Relation between plasma trough concentration of abiraterone and prostate-specific antigen response in metastatic castration-resistant prostate cancer patients. Eur J Cancer. 2017 Feb;72:54-61. doi: 10.1016/j.ejca.2016.11.027. Epub 2016 Dec 24.

  PMID: 28027516 BACKGROUND

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Abiraterone Acetate

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Jerome ALEXANDRE, MD PhD

  Paris Descartes University, Assistance Publique Hôpitaux de Paris, Cochin hospital

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 2, 2018
• First Posted: March 8, 2018
• Study Start: June 22, 2018
• Primary Completion: April 29, 2021
• Study Completion: December 27, 2021
• Last Updated: September 5, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)