Carboplatin in mCRPC
- Conditions
- metastatic prostate cancer castration resistantMedDRA version: 20.0 Level: SOC Classification code 10029104 Term: Neoplasms benign, malignant and unspecified (incl cysts and polyps) System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.1 Level: PT Classification code 10036909 Term: Prostate cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.1 Level: LLT Classification code 10076506 Term: Castration-resistant prostate cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-002104-40-ES
- Lead Sponsor
- Centro Nacional de Investigaciones Oncológicas (CNIO)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Not specified
- Target Recruitment
- 150
Pre-screening Inclusion Criteria:
• Signed prescreening informed consent form
• Male =18 years old
• Histologically, or cytologically, confirmed adenocarcinoma of the prostate
• Evidence of metastatic CRPC amenable for tumors biopsies, with distant metastases documented by radionuclide bone scan, CT scan or MRI
• Ongoing therapy with luteinizing hormone releasing hormone (LH-RH) analogue or bilateral orchiectomy with serum testosterone < 50 ng/dl. If the method of castration is LH-RH analogue, the patient must be willing to continue the use of LH-RH agonists if he starts on study treatment.
• Patients treated or who are receiving systemic treatment for Prostate Cancer which include at least 1 taxane-based chemotherapy and 1 ARSi (enzalutamide and/or abiraterone acetate/prednisone and/or apalutamide and/or darolutamide). Patients could have had this treatment either as consecutive single agent or in combination, either for mHSPC, mCRPC or nmCRPC but must have received at least 12 weeks of chemotherapy and ARSi or be intolerant to one and/or both
• Unconfirmed biochemical/radiographic progression or clinical progression
• According to the treating physician and institutional protocols, the subject is fit and there are no contraindications to undergo a biopsy procedure
• Adequate coagulation: INR or PT = 1.5 x ULN. Patients ongoing anticoagulant therapy must switch to low molecular weight heparin at least one week before doing biopsy
• ECOG performance status =2
• Subjects must agree to undergo all the study procedures, including the fresh-tumor biopsy
Cohort A additional inclusion criteria
• Patients eligible to Cohort A (with previously known DDR) must have received at least one PARP inhibitor
Inclusion Criteria (screening):
• Pre-screening inclusion criteria
• Patients must have progressive disease defined as at least one of the following:
- Progressive measurable disease by RECIST 1.1
- Bone scan progression according to the PCWG3 criteria
- A =25% increase in PSA with an absolute increase of =2 ng/mL from the nadir, and which is confirmed by a second value =3 weeks later according to the PCWG3
• Adequate haematological function: platelet count =100.000/mm3, absolute neutrophil count (ANC) =1.500/mm3, haemoglobin =9g/dL without receiving more than 1 transfusion in the last 4 weeks
• Adequate liver function: alanine aminotransferase (ALT) or aspartate aminotransferase (AST) =2.5 x upper limit of normal (ULN), bilirubin (total) =2 x ULN, or = 5 times the ULN if liver metastases are present
• Adequate renal function: for subjects with serum creatinine >1.5 x ULN, calculated creatinine clearance must be >30 ml/min (Gault and Cockroft method)
• Subjects capable of maintaining sexual intercourse and therefore of fathering children, must agree to use an effective method of contraception for the duration of the trial and 6 months after last dose
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 75
Pre-screening Exclusion Criteria:
• Prior treatment with PARP-inhibitors, except for those patients eligible for Cohort A
Exclusion Criteria (screening):
• Pre-screening exclusion criteria
• Previous cancer diagnosis, except those patients who had a localized malignant tumor and who are five years cancer-free or those diagnosed with skin cancers (of non-melanoma type) or excised in situ or non-muscle invasive bladder cancer (NIMBC) who has had definitively curative treatment
• Any prior medical history that according to the judgement of the investigator might interfere with the subject’s granting of informed consent or the safe execution of the procedures required in the study
• Other serious illness(es) involving cardiac, respiratory, central nervous system, renal, hepatic or haematological organ systems which might preclude completion of this study or interfere with determination of causality of any adverse effects experienced in this study
• Uncontrolled progressive thrombo-embolic disease or active uncontrolled infection
• Grade > 1 peripheral neuropathy or any prior/concurrent toxicity which may interfere with the safety assessment or lead to premature carboplatin discontinuation
• Known brain or leptomeningeal involvement unless clinically stable and on stable dose of steroids
• Hypersensitivity to carboplatin or any compound containing platinum
• Use of systemic chemotherapeutic (including but not limited to taxanes), hormonal, biologic, or radionuclide therapy for treatment of metastatic prostate cancer (other than approved bone-targeting agents and GnRH agonist/antagonist) or any other investigational agent within 4 weeks or 5 times drug median half-life if shorter before Day 1
• Subjects who have any previous treatment with DNA-damaging cytotoxic chemotherapy (ie, platinum-derivatives, mitoxantrone, cyclophosphamide), except if for non-prostate cancer indication and last dose > 5 years prior to randomization
• Patients with previous =25 % bone marrow irradiation within the 4 weeks prior to planned start of treatment
• Major surgery within 28 days prior to the first dose of Carboplatin
• Known Hepatitis B surface antigen (HBsAg) or positive hepatitis C antibody or HIV
• Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method