Multiparametric Assessment of Bone Response in mCRPC Patients Treated With Cabozantinib

NCT05265988 | Completed Phase 2

• 1 other identifier: ASSTBS-FARM-ONC-MERIDIAN-2020
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief 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

Conditions

Carcinoma Prostate

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Objective response rate (ORR) on bone metastases through bone scan.

  12 months.

• Quality of life through the administration of validated questionnaires.

  12 months

• Progression free survival (PFS).

  From randomization to first evidence of progression or death from any cause.

• Overall survival (OS).

  From randomization to death from any cause.

• Incidence of skeletal related events (SRE).

  12 months.

Study Arms (1)

Meridian

EXPERIMENTAL

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

Drug: Cabozantinib

Interventions

Cabozantinib DRUG

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

Also known as: Cabozantinib 40/20 mg tablet

Meridian

Eligibility Criteria

• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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),

Sponsors & Collaborators

• Alfredo Berruti: lead

Study Sites (1)

Alfredo Berruti

Brescia, 25123, Italy

Location

Related Publications (18)

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• Smith M, De Bono J, Sternberg C, Le Moulec S, Oudard S, De Giorgi U, Krainer M, Bergman A, Hoelzer W, De Wit R, Bogemann M, Saad F, Cruciani G, Thiery-Vuillemin A, Feyerabend S, Miller K, Houede N, Hussain S, Lam E, Polikoff J, Stenzl A, Mainwaring P, Ramies D, Hessel C, Weitzman A, Fizazi K. Phase III Study of Cabozantinib in Previously Treated Metastatic Castration-Resistant Prostate Cancer: COMET-1. J Clin Oncol. 2016 Sep 1;34(25):3005-13. doi: 10.1200/JCO.2015.65.5597. Epub 2016 Jul 11.

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  PMID: 22826385 RESULT

• Padhani AR, Makris A, Gall P, Collins DJ, Tunariu N, de Bono JS. Therapy monitoring of skeletal metastases with whole-body diffusion MRI. J Magn Reson Imaging. 2014 May;39(5):1049-78. doi: 10.1002/jmri.24548. Epub 2014 Feb 10.

  PMID: 24510426 RESULT

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  PMID: 24772219 RESULT

• Senn C, Gunther B, Popp AW, Perrelet R, Hans D, Lippuner K. Comparative effects of teriparatide and ibandronate on spine bone mineral density (BMD) and microarchitecture (TBS) in postmenopausal women with osteoporosis: a 2-year open-label study. Osteoporos Int. 2014 Jul;25(7):1945-51. doi: 10.1007/s00198-014-2703-8. Epub 2014 Apr 24.

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• Di Gregorio S, Del Rio L, Rodriguez-Tolra J, Bonel E, Garcia M, Winzenrieth R. Comparison between different bone treatments on areal bone mineral density (aBMD) and bone microarchitectural texture as assessed by the trabecular bone score (TBS). Bone. 2015 Jun;75:138-43. doi: 10.1016/j.bone.2014.12.062. Epub 2015 Jan 6.

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• 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.jocd.2015.06.013.

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• Perdomo G, Martinez-Brocca MA, Bhatt BA, Brown NF, O'Doherty RM, Garcia-Ocana 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.M707551200. Epub 2008 Mar 24.

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• Vega A, Abad S, Macias N, Aragoncillo I, Santos A, Galan I, Cedeno S, Manuel Lopez-Gomez J. Low lean tissue mass is an independent risk factor for mortality in patients with stages 4 and 5 non-dialysis chronic kidney disease. Clin Kidney J. 2017 Apr;10(2):170-175. doi: 10.1093/ckj/sfw126. Epub 2017 Feb 8.

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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.

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MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

cabozantinib; Tablets

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations

Study Officials

• Alfredo Berruti

  Asst Degli Spedali Civili Di Brescia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Masking Details: The patients are treated in one arm.
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director of the Medical Oncology Unit

Model Details: Monocentrici Study. The patients are treated in one arm

Study Record Dates

• First Submitted: February 17, 2022
• First Posted: March 4, 2022
• Study Start: November 29, 2021
• Primary Completion: June 29, 2024
• Study Completion: June 29, 2024
• Last Updated: July 31, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)