ProBio: An outcome-adaptive and randomised multi-arm biomarker driven study in patients with metastatic prostate cancer

Phase 1

• Conditions: patients with metastatic hormonesensitive (mHSPC) and metastatic castration-resistant (mCRPC) prostate cancer starting a new line of systemic therapy.; MedDRA version: 21.1Level: 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: EUCTR2018-002350-78-BE
• Lead Sponsor: Karolinska Institute

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2020-02-12
• Last Update Posted: 8 July 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Male
• Target Recruitment: 2700

Inclusion Criteria

1. Male patients, aged above 18 years, with histologically confirmed prostate adenocarcinoma, initiating systemic therapy for metastatic disease, encompassing:
- Newly diagnosed (i.e. de novo) metastatic hormone- sensitive prostate cancer (mHSPC) who are ADT-naive at enrolment and liquid biopsy collection
or
- First-line mCRPC, i.e. first evidence of progressive metastatic prostate cancer under castrate levels (<50 ng/dL or 1.7 nmol/L) of serum testosterone, regardless which prior therapy exposure in the localized, mHSPC, or nmCRPC setting; and as defined by the EAU guidelines, encompassing:
? Biochemical progression: Three consecutive rises in PSA 1 wk apart, resulting in two 50% increases over the nadir, and PSA >2 ng/ml and/or
? Radiologic progression: The appearance of new lesions: either two or more new bone lesions on bone scan or a soft tissue lesion using the Response Evaluation Criteria in Solid Tumours

2. Distant metastatic disease documented by conventional imaging, i.e. positive bone scan or metastatic lesions on CT or MRI. Radiology taken within 6 weeks of screening may be used, if older a new scan needs to be taken. With the advent of novel imaging modalities using radionuclides, e.g. PSMA PET/CT, the ProBio trial will allow for future incorporation of these imaging modalities upon availability of validated guidelines, progression criteria and protocol amendment. PSMA PET/CT can be used for initial identification of patients with metastatic disease, but a positive finding on PSMA PET/CT needs to be confirmed on conventional CT and/or bone scan. Patients with PSMA PET/CT only positive disease cannot be included in ProBio.

3. Adequate health, hematologic, hepatic, and renal function, as assessed by the investigator, to receive all available treatments in the trial in each disease state (mHSPC and mCRPC), i.e.
- Haemoglobin = 100 g/L (blood transfusion not less than 21 days prior to screening)
- Absolute neutrophil count = 1.5 x 10^9/L
- Platelets =100 x 10^9/L
- Total bilirubin < 1.5 ULN (patients with Gilbert's Syndrome bilirubin < 40 µg/L)
- AST and ALT = 1.5 ULN (or = 3 ULN in the presence of liver metastases)
- Serum creatinine not greater than 1 ULN (if serum creatinine is between 1 and 1.5 ULN, patients may be eligible provided that the calculated GFR is at least 50 ml/min measured directly by 24-hour urine sampling OR using Cockcroft-Gault method)

4. Albumin greater than or equal to 28 g/L

5. ECOG/WHO performance score 0-2

6. Agrees to use an effective contraceptive method during and up to 6 months after study drug treatment and should not donate sperm during this period.

7. Able to understand the patient information and sign written informed consent.
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 70
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 280

Exclusion Criteria

1. Other malignancies within 5 years except non-melanoma skin cancer

2. Within 6 months of randomisation: myocardial infarction, unstable angina, angioplasty, bypass surgery, stroke, TIA, or congestive heart failure NYHA class III or IV.

3. Uncontrolled hypertension: SBP > 160 mmHg and or DBP > 95 mmHg. Subjects with a history of hypertension are allowed provided blood pressure is controlled by anti-hypertensive treatment.

4. Uncontrolled hypotension: SBP < 90 mmHg and/or DBP < 50 mmHg.

5. Upon entering the mHSPC phase of the trial, prior systemic therapy (including ADT) is not allowed. Patients with mCRPC may not enter the trial when they have already received prior systemic therapy (with the exception of standard ADT) for mCRPC.

6. Any severe acute or chronic medical condition that places the patient at increased risk of serious toxicity or interferes with the interpretation of study results. This includes a medical history significant for arrhythmia (e.g. multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia), which is symptomatic or requires treatment (CTCAE Grade 3), symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia. Participants with atrial fibrillation controlled by medication or arrhythmias controlled by pacemakers may be permitted to enter the study based on the Investigators judgement with cardiologist consultation recommended.

7. Unable to comply with study procedures.

8. Current participation in another clinical trial that will be in conflict with the present study, e.g. administration of an investigational therapeutic or invasive surgical procedure within 28 days prior to study enrolment. Imaging-based interventional trials are allowed as long as the conventional imaging intervals within ProBio are preserved.

9. Patients who are unlikely to comply with the protocol (e.g. uncooperative attitude, inability to return for subsequent visits) and/or otherwise considered by the Investigator to be unlikely to complete the study

10. Any condition or situation which, in the opinion of the investigator, would put the subject at risk, may confound study results, or interfere with the subject’s participation in this study. This includes a history of QT prolongation associated with other medications that required discontinuation of that medication; and other factors that increase the risk of QTc prolongation or risk of arrhythmic events, hypokalemia of grade >1, potential for Torsade de Pointes, congenital long QT syndrome.

10. Any condition or situation which, in the opinion of the investigator, would put the subject at risk, may confound study results, or interfere with the subject’s participation in this study. This includes a history of QT prolongation associated with other medications that required discontinuation of that medication; and other factors that increase the risk of QTc prolongation or risk of arrhythmic events, hypokalemia of grade >1, potential for Torsade de Pointes, congenital long QT syndrome.

11. Any medical condition that would make use of the study treatments contraindicated, according to the SmPC, e.g. significant heart or liver disease. The investigator should check the SmPC and/or IB for the assigned study treatments. This includes a family history of long QT syndrome, or unexplained sudden death under 40 years of age in first-degree relatives.

12. The determination of a biomarker signature is

Study & Design

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