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Multiparametric assessment of bone response in mCRPC patients treated with Cabozantinib upon progression to chemotherapy and next generation hormonal agents

Phase 1
Conditions
PATIENTS WITH BONE METASTASIS FROM PROSTATIC CARCINOMA
MedDRA version: 20.0Level: SOCClassification code 10029104Term: Neoplasms benign, malignant and unspecified (incl cysts and polyps)System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]
Registration Number
EUCTR2021-000520-35-IT
Lead Sponsor
AZIENDA SOCIO SANITARIA TERRITORIALE DEGLI SPEDALI CIVILI DI BRESCIA
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
Authorised-recruitment may be ongoing or finished
Sex
Male
Target Recruitment
30
Inclusion Criteria

1. Histological diagnosis of prostate carcinoma,
2. Age > 18 years,
3. Metastatic disease documented as the presence of bone lesions on bone scan associated or not to soft tissue lesions measurable at CT/RMN,
4. Eastern Cooperative Oncology Group (ECOG) performance status equal or less than 2
5. Expected life expectancy = 3 months,
6. Patients who have already received docetaxel, cabazitaxel and at least one next generation hormonal agent (abiraterone or enzalutamide) for metastatic disease (either hormone sensitive or castration resistant),
7. Subject capable to swallow the Study's medication and to comply with the Study's requirements,
8. Fertile patients and their partners must agree to use methods of contraception.
9. Signed 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 15
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 15

Exclusion Criteria

Presence of active serious disease, active infection or co-comorbidity that may prevent the study enrollment make
2. Known or suspected brain metastases or active leptomeningeal dissemination,
3. History of other malignant neoplasm during the previous 5 years, different from the non-melanoma skin carcinoma,
4. Absolute Neutrophil Count (ANC) < 1.500/µL, platelet < 100.000/µL, or hemoglobin < 5,6 mmol/L (< 9 g/dL) at Screening Visit (notably: patients must not receive neither any growth factor during the previous 7 days nor any blood transfusion during the 28 days preceding the hematology sampling performed at Screening),
5. Total bilirubin > 1,5 x ULN at Screening Visit,
6. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2,5 x ULN at Screening Visit,
7. Creatinine > 177 µmol/L (> 2 mg/dL) at Screening Visit,
8. Albumin = 30 g/L (= 3,0 g/dL) at Screening Visit,
9. Alkaline Phosphatase = 5 x ULN,
10. Prothrombin time / international normalized ratio (PT/INR) or partial thromboplastin time (PTT) test = 1.3 x the laboratory ULN,
11. Urine protein-to-creatinine ratio (UPCR) > 1 mg/mg (or 113.0 mg/mmol) or proteinuria > 1 g/24 h,
12. History of seizures or any other seizure-predisposed pathology; history of loss of consciousness or transitory ischaemic attack during the 12 months preceding the Screening visit,
13. Clinically significant cardiovascular disease including
- Myocardial infarction - Uncontrolled angina - Congestive heart failure New York Heart Association (NYHA) class 3 or 4, congestive heart failure NYHA class 3 or 4 in the past, unless a screening echocardiogram or multi-gated acquisition scan performed within three months results in a left ventricular ejection fraction that is = 45%,- History of clinically significant ventricular arrhythmias
- History of long QT syndrome or corrected QT interval calculated by the Fridericia formula > 500 msec at Screening Visit,
- History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place,
- Hypotension as indicated by systolic blood pressure < 86 millimeters of mercury (mmHg) at the Screening visit,
- Bradycardia as indicated by a heart rate of < 50 beats per minute on the Screening ECG,
- Uncontrolled hypertension as indicated by systolic blood pressure > 170 mmHg or diastolic blood pressure > 105 mmHg at the Screening visit,
14. Gastrointestinal disorder affecting absorption
15. Major surgery within 4 weeks of enrollment
16. Concomitant therapy with anticoagulants
,17. Use of herbal products that may have hormonal anti-prostate cancer activity and/or are known to decrease PSA levels (e.g., saw palmetto) or systemic corticosteroids greater than the equivalent of 10 mg of prednisone per day within four weeks of enrollment
18. Bone antiresorptive drugs that are started within 4 weeks of enrollment Bone antiresorptive drugs are permitted if already ongoing before this time point. Patients will be stratified according to zoledronic acid/denosumab exposure.
19. Systemic treatment with radionuclides within 6 weeks before first dose of study treatment or radiotherapy on sites other than bone administrated within 4 weeks of enrollment (Day 1 Visit). Radiotherapy on bone administrated within 2 weeks of enrollment. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible. Radiotherapy given with palliative intent will be permitted during study treatment.
20. Any condition or reason that, i

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Secondary Outcome Measures
NameTimeMethod
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