Tests prostate cancer drugs chosen by tumor gene changes

AI summary

From the trial's eligibility criteria. Machine-read from the registry text on this page, so it can be wrong. The registry text below and the trial team decide who can take part.

The trial is looking for men whose prostate cancer has spread to other parts of the body and who are about to start drug treatment for it.

Age

18 years or older

Sex

Men only

Disease stage

Prostate adenocarcinoma that has spread to distant parts of the body, shown by bone scan, CT or MRI. Either newly diagnosed hormone-sensitive disease or first-line castration-resistant disease.

Earlier treatment

Cannot have had drug treatment for castration-resistant prostate cancer before joining, apart from standard ADT.

Main reasons for not taking part

• Another cancer within the last 5 years, except non-melanoma skin cancer
• Heart attack, unstable angina, stroke or severe heart failure within 6 months before randomization
• Uncontrolled high or low blood pressure
• Taking part in another clinical trial that conflicts with this one, or an investigational treatment or invasive surgery within 28 days before joining
• Any condition that would make the study treatments unsafe, such as significant heart or liver disease

The registry criteria, word for word

What the trial wants to find out

ProBio is an international, outcome-adaptive, multi-arm, open-label, multiple assignment randomized biomarker driven platform trial in patients with metastatic prostate cancer. Patients will be randomized to control or experimental treatment arms. Patients in the control arm will receive standard of care following national guidelines. Patients in the experimental arm will be randomized to treatments based on a biomarker signature inferred from diagnostic tissue or liquid biopsy profiling. The predefined biomarker signatures are tumor properties or mutations in genes/pathways with previously demonstrated clinical validity (e.g. prognostic value or association with treatment response). The biomarker signatures are identified using a hybridisation capture gene panel specifically designed for prostate cancer.

The 8 groups in the trial

• Control: Standard CareExisting treatment, for comparison

  Randomization between assignment to the control arm or the biomarker driven arm will be stratified on biomarker signatures, previous treatment, and fraction of ctDNA and will therefore occur after the results from the ctDNA profiling is obtained. Patients in the control arm will receive standard of care following national guidelines.

  Treatment: Enzalutamide Oral Capsule, Abiraterone Oral Tablet, Cabazitaxel 60 mg Solution for Injection, Docetaxel Injectable Solution, Radium Chloride Ra-223, and Apalutamide

• Treatment 1 in mHSPC: AR signalling inhibitors (ARSi)Treatment being tested

  Assignments to therapy in the biomarker driven arms will be done on the basis of the biomarker signature using the current information about the efficacy of the various regimens for that signature. Information from previous studies may be incorporated in the randomization at study onset if such reliable data exists. Specifically, patients with an intact androgen receptor (AR) and without TP53 mutations will have increased chance of being randomized to treatment with ARSi.

  Treatment: Enzalutamide Oral Capsule, Abiraterone Oral Tablet, and Apalutamide

• Treatment 2 in mHSPC: taxane-based chemotherapy in combination with ARSiTreatment being tested

  Patients with TP53 mutations and TMPRSS2-ERG gene fusions will have an increased chance of being randomised to treatment with chemotherapy plus an ARSi.

  Treatment: Abiraterone Oral Tablet, Docetaxel Injectable Solution, and Darolutamide

• Treatment 3 in mHSPC: Poly ADP Ribose Polymerase (PARP) inhibitorTreatment being tested

  DNA-repair deficient patients will have an increased chance of receiving PARP inhibitors at study onset.

  Treatment: Niraparib plus Abiraterone acetate plus Prednisone

• Treatment 1 in mCRPC: AR signalling inhibitors (ARSi)Treatment being tested

  Specifically, patients with an intact androgen receptor (AR) and without TP53 mutations will have increased chance of being randomized to treatment with ARSi.

  Treatment: Enzalutamide Oral Capsule and Abiraterone Oral Tablet

• Treatment 2 in mCRPC: Poly ADP Ribose Polymerase (PARP) inhibitorTreatment being tested

  DNA-repair deficient patients will have an increased chance of receiving PARP inhibitors at study onset.

  Treatment: Niraparib plus Abiraterone acetate plus Prednisone

• Treatment 3 in mCRPC: selective AKT InhibitorTreatment being tested

  Patients with alterations in the PI3K pathway will have an increased chance of receiving the combination treatment with Capivasertib plus Docetaxel.

  Treatment: Capivasertib plus Docetaxel

• Treatment 4 in mCRPC: CarboplatinTreatment being tested

  Only patients with DNA-repair deficiency will be treated with Carboplatin as second line treatment in the castration-resistant phase of ProBio.

  Treatment: Carboplatin