Intra-individual dose escalation of abiraterone acetate according to its concentration in blood in patients with progressive castration-resistant metastatic prostate cancer

Phase 1

Active, not recruiting

• Conditions: Metastatic castration-resistant prostate carcinoma men, aged >/= 18 years; MedDRA version: 20.0Level: PTClassification code 10036909Term: Prostate cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2017-000560-15-FR
• Lead Sponsor: ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS (AP-HP)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2018-01-12
• Last Update Posted: 2022-01-17

Recruitment & Eligibility

• Status: Not Recruiting
• Sex: Male
• Target Recruitment: 175

Inclusion Criteria

Step 1
- Male 18 years and older.
- Voluntary signed informed consents of the patient
- Histologically confirmed prostate adenocarcinoma.
- Presence of bone and/or soft-tissue and/or visceral metastases through CT scan, MRI, or scintigraphy scan.
- Progressive disease assessed by PSA, CT scan, MRI or bone scan according to the PCGW3 criteria
- Patient with no or moderate symptoms (no need for continuous opioid treatment)
- Effective castration confirmed by testosterone plasma level < 50 ng/mL
- ECOG performance status: 0-2
- Life expectancy > 3 months
- Patient affiliate to french social secutity
- Laboratory criteria:
SGPT and SGOT < 5 fold the upper normal value
Kaliemia > 3 mM
Step 2
- Patients receiving ABI 1000 mg/day through step 1 for at least two months
- At least two measures of ABI plasma concentrations available within the first three months of treatment
- Mean of ABI concentration < 8,5ng/mL.
- Progressive disease according to PCWG3 criteria within 28 weeks following starting of ABI in the step 1 (according to PCWG3 criteria of progression at trial entry, isolated PSA increase will be accepted).
- Inclusion in step 2 must occur within 2 months following the first observation of cancer progression while in step 1.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

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 performed on the day of screening or within previous four weeks.
- Patient co-morbidities:
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%
Severe hypokaliema

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 the protocol.
Step 2
- Persistent grade 3-4 toxicities related to ABI. In case of persistent grade 2 toxicity or resolutive grade 3-4 toxicities, inclusion in step 2 must be discussed in a case by case basis with the study coordinating Investigator.
- All non-inclusion criteria for step 1 apply
- Patient who does not take ABI daily at the investigator opinion

Study & Design

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