Multiparametric Assessment of Bone Response in mCRPC Patients Treated With Cabozantinib

Carcinoma Prostate Clinical Trial

— MERIDIAN  

Official title:

Multiparametric Assessment of Bone Response in mCRPC Patients Treated With Cabozantinib Upon Progression to Chemotherapy and Next Generation Hormonal Agents: a Phase II Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05265988
• Other study ID #: ASSTBS-FARM-ONC-MERIDIAN-2020
• Status: Recruiting
• Phase: Phase 2
• Start date: October 29, 2021
• Est. completion date: October 29, 2023

Study information

• Verified date: March 2022
• Source: Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
• Contact: Aldo Roccaro
• Phone: +390303996851
• Email: coordinamento.ricerca[@]asst-spedalicivili.it
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Multiparametric assesment of bone response in mCRPC patients treated with Cabozantinib upon progression to chemotherapy and next generation hormonal agents: a phase II study

Description:

This is a monocentric, single arm, prospective clinical trial designed to obtain explorative information about the effect of Cabozantinib on bone in prostate cancer patients with bone metastatic castration resistant disease, previously treated with two taxanes and at least one next generation hormonal agent. Activity of bone metastatic disease will be assessed by WB-DW-MRI, while changes in bone metabolism will be studied through DXA scan and soluble biomarkers

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 32
• Est. completion date: October 29, 2023
• Est. primary completion date: October 29, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Histological diagnosis of prostate carcinoma,
• Age > 18 years,
• Metastatic disease documented as the presence of bone lesions o bone scan associated or not to soft tissue lesions measurable at CT/RMN,
• Eastern Cooperative Oncology Group (ECOG) performance status equal or less than 2
• Expected life expectancy = 3 months,
• 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),
• Subject capable to swallow the Study's medication and to comply with the Study's requirements,
• Fertile patients and their partners must agree to use methods of contraception.
• Signed informed consent.

Exclusion Criteria:

• Presence of active serious disease, active infection or co-comorbidity that may prevent the study enrollment make (at the discretion of the clinical Investigator),
• Known or suspected brain metastases or active leptomeningeal dissemination,
• History of other malignant neoplasm during the previous 5 years, different from the non-melanoma skin carcinoma,
• 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),
• Total bilirubin > 1,5 x ULN at Screening Visit,
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2,5 x ULN at Screening Visit,
• Creatinine > 177 µmol/L (> 2 mg/dL) at Screening Visit,
• Albumin = 30 g/L (= 3,0 g/dL) at Screening Visit,
• Alkaline Phosphatase = 5 x ULN,
• Prothrombin time / international normalized ratio (PT/INR) or partial thromboplastin time (PTT) test = 1.3 x the laboratory ULN,
• Urine protein-to-creatinine ratio (UPCR) > 1 mg/mg (or 113.0 mg/mmol) or proteinuria > 1 g/24 h,
• 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,
• Clinically significant cardiovascular disease including:
• Myocardial infarction (6 months preceding the screening),
• Uncontrolled angina (3 months preceding the screening),
• 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 (e.g., ventricular tachycardia, ventricular fibrillation, torsades de pointes),
• 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,
• History of thromboembolic events, including pulmonary embolism or untreated deep venous thrombosis (6 months preceding the screening)
• Gastrointestinal disorder affecting absorption (e.g., gastrectomy, active peptic ulcer disease within last 3 months),
• Major surgery within 8 weeks of enrollment (Day 1 Visit). Complete healing from major surgery must have occurred 4 weeks before enrollment. Complete healing from minor surgery (e.g. simple excision, tooth extraction) must have occurred at least 7 days before enrollment.
• Subjects with clinically relevant complications from prior surgery.
• Concomitant therapy with anticoagulants such as warfarin or warfarin-related agents, thrombin or coagulation factor X (FXa) inhibitors, or antiplatelet agents (e.g. clopidogrel). Low molecular weight Heparin (LMWH) and low-dose aspirin for cardioprotection (per local applicable guidelines) are permitted.
• Concomitant use of strong inhibitors of CYP3A4 (including, but not limiting to:

ketoconazole, itraconazole, clarithromycin, indinavir, nefazodone, nelfinavir, and ritonavir).

• 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 4 weeks of enrollment (Day 1 visit).
• Previously identified allergy or hypersensitivity to the study drug and/or excipients.
• Bone antiresorptive drugs (e.g., zoledronic acid or denosumab) that are started within 4 weeks of enrollment (Day 1 Visit). Bone antiresorptive drugs are permitted if already ongoing before this time point. Patients will be stratified according to zoledronic acid/denosumab exposure.
• 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.
• Any condition or reason that, in the opinion of the Investigator, interferes with the ability of the patient to participate in the trial, which places the patient at undue risk, or complicates the interpretation of safety data.

Related Conditions & MeSH terms

• Carcinoma Prostate
• Prostatic Neoplasms

Intervention

Drug:
• Cabozantinib
Cabozantinib at initial dosage of 40 mg per day and continuation of androgen deprivation therapy

Locations

Country	Name	City	State
Italy	Alfredo Berruti	Brescia

Sponsors (1)

Lead Sponsor	Collaborator
Alfredo Berruti

Country where clinical trial is conducted

Italy, 

References & Publications (18)

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Perdomo G, Martinez-Brocca MA, Bhatt BA, Brown NF, O'Doherty RM, Garcia-Ocaña A. Hepatocyte growth factor is a novel stimulator of glucose uptake and metabolism in skeletal muscle cells. J Biol Chem. 2008 May 16;283(20):13700-6. doi: 10.1074/jbc.M70755120 — View Citation

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Shepherd JA, Ng BK, Sommer MJ, Heymsfield SB. Body composition by DXA. Bone. 2017 Nov;104:101-105. doi: 10.1016/j.bone.2017.06.010. Epub 2017 Jun 16. — View Citation

Shepherd JA, Schousboe JT, Broy SB, Engelke K, Leslie WD. Executive Summary of the 2015 ISCD Position Development Conference on Advanced Measures From DXA and QCT: Fracture Prediction Beyond BMD. J Clin Densitom. 2015 Jul-Sep;18(3):274-86. doi: 10.1016/j. — View Citation

Shiozawa Y, Pedersen EA, Havens AM, Jung Y, Mishra A, Joseph J, Kim JK, Patel LR, Ying C, Ziegler AM, Pienta MJ, Song J, Wang J, Loberg RD, Krebsbach PH, Pienta KJ, Taichman RS. Human prostate cancer metastases target the hematopoietic stem cell niche to — View Citation

Smith M, De Bono J, Sternberg C, Le Moulec S, Oudard S, De Giorgi U, Krainer M, Bergman A, Hoelzer W, De Wit R, Bögemann M, Saad F, Cruciani G, Thiery-Vuillemin A, Feyerabend S, Miller K, Houédé N, Hussain S, Lam E, Polikoff J, Stenzl A, Mainwaring P, Ram — View Citation

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* Note: There are 18 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective response rate (ORR) on bone metastases through whole body diffusione weighted (WB-DW) MRI.	Proportion of patients attaining a partial or complete response to therapy on bone metastases by means of WB-DW MRI.	6 months
Secondary	Objective response rate (ORR) on bone metastases through bone scan.	Proportion of patients attaining a partial or complete response to therapy on bone metastases by means of bone scan.	12 months.
Secondary	Quality of life through the administration of validated questionnaires.	Change in bone pain and quality of life through the administration of validated questionnaires.	12 months
Secondary	Progression free survival (PFS).	Time from treatment initiation and disease progression or death from any cause.	From randomization to first evidence of progression or death from any cause.
Secondary	Overall survival (OS).	Time from treatment initiation and death from any cause.	From randomization to death from any cause.
Secondary	Incidence of skeletal related events (SRE).	Proprtion of SRE defined as the occurrence of one among: spinal cord compression, pathologic fracture, necessity for radiation to bone or surgery to bone.	12 months.