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Carcinoma ProstatePhase 2MERIDIANNCT05265988

Multiparametric Assessment of Bone Response in mCRPC Patients Treated With Cabozantinib

A Phase 2 study testing Cabozantinib in people with Carcinoma Prostate, run by Alfredo Berruti at 1 site in Italy.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

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 Read more about this study

Who is it for?
Any age, men onlyHealthy volunteers can take part
Conditions the study is for
Carcinoma Prostate
What is being tested?
Cabozantinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
32 participants
Where
1 siteItaly
Study dates
29 Nov 2021to 29 Jun 2024
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Any age
  • Men only
  • Healthy volunteers accepted
  • Child, Adult, Older adult

Who may be able to join

  • 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),
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  • 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.

Who cannot join

  • 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,
Show all 33Show fewer
  • 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.

Trial locations and contacts

1 site in 1 country.

Italy1 site

  • Alfredo Berruti

    Brescia, 25123

Other trials in Italy

About this study

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

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

Read the 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

Being tested
Cabozantinib
Medical subject headings
Prostatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CabozantinibDrug

    Also called Cabozantinib 40/20 mg tablet

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

Study groups in NCT05265988
Study groupRoleWhat they receive
MeridianExperimentalCabozantinib at initial dosage of 40 mg per day and continuation of androgen deprivation therapy
Receives: Drug: Cabozantinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 6 months

Secondary outcomes (5)

  1. 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.

    Measured: 12 months.

  2. Quality of life through the administration of validated questionnaires.

    Change in bone pain and quality of life through the administration of validated questionnaires.

    Measured: 12 months

  3. Progression free survival (PFS).

    Time from treatment initiation and disease progression or death from any cause.

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

  4. Overall survival (OS).

    Time from treatment initiation and death from any cause.

    Measured: From randomization to death from any cause.

  5. 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.

    Measured: 12 months.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Mar 2022
  2. Study start29 Nov 2021
  3. Primary completion29 Jun 2024
  4. Study completion29 Jun 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
Monocentrici Study. The patients are treated in one arm
Masking
None (open label)
Enrolment
32 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05265988
Sponsor's protocol ID
ASSTBS-FARM-ONC-MERIDIAN-2020
Acronym
MERIDIAN
Status last verified
Jul 2024
First submitted
17 Feb 2022
Last updated
31 Jul 2024
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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 establish footholds in mouse bone marrow. J Clin Invest. 2011 Apr;121(4):1298-312. doi: 10.1172/JCI43414. Epub 2011 Mar 23.

    PubMed 21436587

  • 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.

    PubMed 27400947

  • Schmidt GP, Reiser MF, Baur-Melnyk A. Whole-body MRI for the staging and follow-up of patients with metastasis. Eur J Radiol. 2009 Jun;70(3):393-400. doi: 10.1016/j.ejrad.2009.03.045. Epub 2009 May 19.

    PubMed 19457631

  • Vanel D, Casadei R, Alberghini M, Razgallah M, Busacca M, Albisinni U. MR imaging of bone metastases and choice of sequence: spin echo, in-phase gradient echo, diffusion, and contrast medium. Semin Musculoskelet Radiol. 2009 Jun;13(2):97-103. doi: 10.1055/s-0029-1220880. Epub 2009 May 19.

    PubMed 19455472

  • Ma J. Dixon techniques for water and fat imaging. J Magn Reson Imaging. 2008 Sep;28(3):543-58. doi: 10.1002/jmri.21492.

    PubMed 18777528

  • Koh DM, Blackledge M, Padhani AR, Takahara T, Kwee TC, Leach MO, Collins DJ. Whole-body diffusion-weighted MRI: tips, tricks, and pitfalls. AJR Am J Roentgenol. 2012 Aug;199(2):252-62. doi: 10.2214/AJR.11.7866.

    PubMed 22826385

  • 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.

    PubMed 24510426

  • Huang W, Li X, Chen Y, Li X, Chang MC, Oborski MJ, Malyarenko DI, Muzi M, Jajamovich GH, Fedorov A, Tudorica A, Gupta SN, Laymon CM, Marro KI, Dyvorne HA, Miller JV, Barbodiak DP, Chenevert TL, Yankeelov TE, Mountz JM, Kinahan PE, Kikinis R, Taouli B, Fennessy F, Kalpathy-Cramer J. Variations of dynamic contrast-enhanced magnetic resonance imaging in evaluation of breast cancer therapy response: a multicenter data analysis challenge. Transl Oncol. 2014 Feb 1;7(1):153-66. doi: 10.1593/tlo.13838. eCollection 2014 Feb.

    PubMed 24772219

  • 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.

    PubMed 24760244

  • 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.

    PubMed 25571842

  • 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.

    PubMed 26277847

  • Rosen CJ, Bouxsein ML. Mechanisms of disease: is osteoporosis the obesity of bone? Nat Clin Pract Rheumatol. 2006 Jan;2(1):35-43. doi: 10.1038/ncprheum0070.

    PubMed 16932650

  • Shapses SA, Pop LC, Wang Y. Obesity is a concern for bone health with aging. Nutr Res. 2017 Mar;39:1-13. doi: 10.1016/j.nutres.2016.12.010. Epub 2017 Jan 18.

    PubMed 28385284

  • Tang R, Ma F, Li W, Ouyang S, Liu Z, Wu J. miR-206-3p Inhibits 3T3-L1 Cell Adipogenesis via the c-Met/PI3K/Akt Pathway. Int J Mol Sci. 2017 Jul 14;18(7):1510. doi: 10.3390/ijms18071510.

    PubMed 28708070

  • 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.

    PubMed 18362143

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Cabozantinib in people with Carcinoma Prostate, run by Alfredo Berruti at 1 site in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 33 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 31 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective response rate (ORR) on bone metastases through whole body diffusione weighted (WB-DW) MRI. (time frame: 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05265988, which also lists 18 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jul 2024.

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