Multiparametric Assessment of Bone Response in mCRPC Patients Treated With Cabozantinib (MERIDIAN)

March 2, 2022 updated by: Alfredo Berruti

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

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

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed 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

Study Type

Interventional

Enrollment (Anticipated)

32

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Male

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Meridian
Cabozantinib at initial dosage of 40 mg per day and continuation of androgen deprivation therapy
Drug: Cabozantinib
Cabozantinib at initial dosage of 40 mg per day and continuation of androgen deprivation therapy
Other Names:
  • Cabozantinib 40/20 mg tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective response rate (ORR) on bone metastases through whole body diffusione weighted (WB-DW) MRI.
Time Frame: 6 months
Proportion of patients attaining a partial or complete response to therapy on bone metastases by means of WB-DW MRI.
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective response rate (ORR) on bone metastases through bone scan.
Time Frame: 12 months.
Proportion of patients attaining a partial or complete response to therapy on bone metastases by means of bone scan.
12 months.
Quality of life through the administration of validated questionnaires.
Time Frame: 12 months
Change in bone pain and quality of life through the administration of validated questionnaires.
12 months
Progression free survival (PFS).
Time Frame: From randomization to first evidence of progression or death from any cause.
Time from treatment initiation and disease progression or death from any cause.
From randomization to first evidence of progression or death from any cause.
Overall survival (OS).
Time Frame: From randomization to death from any cause.
Time from treatment initiation and death from any cause.
From randomization to death from any cause.
Incidence of skeletal related events (SRE).
Time Frame: 12 months.
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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Alfredo Berruti

Investigators

  • Principal Investigator: Alfredo Berruti, ASST Spedali Civili, Brescia

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 29, 2021

Primary Completion (Anticipated)

October 29, 2023

Study Completion (Anticipated)

October 29, 2023

Study Registration Dates

First Submitted

February 17, 2022

First Submitted That Met QC Criteria

March 2, 2022

First Posted (Actual)

March 4, 2022

Study Record Updates

Last Update Posted (Actual)

March 4, 2022

Last Update Submitted That Met QC Criteria

March 2, 2022

Last Verified

March 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ASSTBS-FARM-ONC-MERIDIAN-2020

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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