Progression under Olaparib: a randomized phaSE II trIal with docetaxel or carboplatin-docetaxel DOublet in mCRPC patieNts

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Azienda Provinciale Per I Servizi Sanitari

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male

Therapeutic area

Diseases [C] - Neoplasms [C04]

Decision date (initial)

2024-11-18

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Funding sources

APSS Azienda Provinciale per i Servizi Sanitari_ Provincia Autonoma di Trento

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy

To demonstrate the superiority of the combination of docetaxel + prednisone / carboplatin (Arm A) compared to docetaxel + prednisone (Arm B) in patients with mCRPC progressing after one androgen-receptor signaling inhibitor (ARSI) followed by olaparib.

Secondary objectives 1

1. To compare the two study arms by: progression-free survival, overall survival, biochemical response rate, objective response rate, toxicity profile, impact on patients' quality of life, impact on pain

Conditions and MedDRA coding

prostate cancer

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Histologically- or cytologically-confirmed prostate adenocarcinoma.
2. Ability to fill the quality of life questionnaire
3. Written informed consent
4. Metastatic Castration Resistant Prostate Cancer (mCRPC)
5. Previous detection of BRCA mutation
6. Treatment for mCRPC with an ARSI and subsequent treatment with olaparib
7. Progressive disease while receiving Olaparib documented by: I. Increase in measurable disease (RECIST 1.1), and/or II. Appearance of new lesions, including those on bone scan (≥2 new lesions on 2 consecutive bone scans if progression disease diagnosed on bone scan only) consistent with progressive prostate cancer, and/or III. Rising PSA defined as 2 sequential increases above a previous lowest reference value. Each value must be obtained at least 1 week apart. A PSA value of at least 2 ng/ml is required at study entry. For patients evaluated with PET the progressive disease should be documented by at least one of the following criteria: I. appearance of at least two new lesions, and/or II. Increase of ≥30% of the uptake or of the tumoral volume
8. Effective castration (serum testosterone levels ≤0.50 ng/dL) by orchiectomy and/or LHRH agonists or antagonist with or without anti-androgens.
9. Age ≥18 years
10. Performance status ECOG <2

Exclusion criteria 11

1. Prior chemotherapy for prostate cancer
2. Prior isotope therapy, whole pelvic radiotherapy, or radiotherapy to >30% of bone marrow.
3. History of brain metastases, uncontrolled spinal cord compression, or carcinomatous meningitis or new evidence of brain or leptomeningeal disease.
4. Inadequate organ and bone marrow function as evidenced by: a. Hemoglobin <10.0 g/dL b. Absolute neutrophil count <1.5 x 109/L, c. Platelet count <100 x 109/L, d. AST and/or ALT >1.5 x ULN; e. Total bilirubin >1.5 x ULN, f. Serum Creatinine >1.5 x ULN. If creatinine 1.0 - 1.5 x ULN, creatinine clearance will be calculated either according to Cockcroft-Gault formula. Creatinine clearance <60 mL/min will exclude the patient
5. Contraindications to the use of corticosteroid treatment.
6. Clinically significant cardiovascular disease including the following: a. Myocardial infarction within 6 months before screening; b. Uncontrolled angina within 3 months before screening; c. Congestive heart failure New York Heart Association class 3 or 4, or a history of congestive heart failure New York Heart Association class 3 or 4, unless a screening echocardiogram or multigated acquisition scan performed within 3 months before randomization demonstrates a left ventricular ejection fraction ≥ 50%; d. History of clinically significant ventricular arrhythmias (eg, sustained ventricular tachycardia, ventricular fibrillation, torsades de pointes); e. History of Mobitz II second-degree or third-degree heart block without a permanent pacemaker in place; f. Hypotension as indicated by systolic blood pressure < 86 millimeters of mercury (mm Hg) at screening; g. Bradycardia as indicated by a heart rate of < 45 beats per minute on the screening electrocardiogram (ECG) and on physical examination; h. Uncontrolled hypertension as indicated by systolic blood pressure > 170 mm Hg or diastolic blood pressure > 105 mm Hg at screening.
7. Any of the following within 3 months prior to randomization: treatment resistant peptic ulcer disease, erosive esophagitis or gastritis, infectious or inflammatory bowel disease, diverticulitis, pulmonary embolism, or other uncontrolled thromboembolic event.
8. Prior malignancy. Adequately treated basal cell or squamous cell skin or superficial (pTis, pTa, and pT1) bladder cancer are allowed, as well as any other cancer for which chemotherapy has been completed >5 years ago and from which the patient has been disease-free for >5 years.
9. Participation in another clinical trial and any concurrent treatment with any investigational drug within 30 days prior to randomization
10. Inability to ensure follow-up
11. Any other condition which in the judgment of the investigator would place the subject at undue risk or interfere with the study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Rate of patients without disease progression after 4 months from the treatment start according to PCWG3

Secondary endpoints 6

1. Progression free-survival by Kaplan-Meier method
2. Overall survival by Kaplan-Meier method
3. Biochemical response rate
4. Objective response rate according to RECIST criteria
5. Adverse events type and grade according to CTCAE v.5
6. Scales of FACT-P and BPI questionnaires

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Auxiliary 8

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Azienda Provinciale Per I Servizi Sanitari

Sponsor organisation

Azienda Provinciale Per I Servizi Sanitari

Address

Via Alcide De Gasperi 79

City

Trento

Postcode

38123

Country

Italy

Scientific contact point

Organisation

Azienda Provinciale Per I Servizi Sanitari

Contact name

Orazio Caffo

Public contact point

Organisation

Azienda Provinciale Per I Servizi Sanitari

Contact name

Orazio Caffo

Locations

1 EU/EEA country · 11 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 28 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications