Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Antineoplastic Agents

All Drugs and Chemicals

Anti-Inflammatory Agents

Docetaxel

Prednisone

Tubulin Modulators

Antimitotic Agents

radium-223 initially followed by docetaxel plus prednisone at the time of progression (PD)

docetaxel plus prednisone initially followed by radium-223 at the time of progression (PD)

Radium-223: administered at the dose of 55 kBq per kg body weight, given at 4 week intervals for 6 injections, by slow intravenous injection

Radium-223

Docetaxel: administered at the dose of 75 mg/m2 by intravenous infusion over a period of 1 hour every 3 weeks for 10 cycles. It is associated with prednisone 5 mg orally twice daily administered continuously.

Oriana Nanni

Ugo de Giorgi, MD

Ugo De Giorgi, MD

Vincenzo Emanuele Chiuri

Paolo Andrea Zucali

Orazio Caffo

Consuelo Buttigliero

Stefania Gori, MD

Matteo Salgarello, MD

Lucia Fratino, MD

Eugenio Borsatti, MD

Susanne Baier, MD

Mohsen Farsad, MD

Giuseppe Fornarini

Franco Nole

Donatello Gasparro, MD

Livia Ruffini, MD

Luca Galli, MD

Giuseppe Boni, MD

Vincenza Conteduca, MD

Randomized, multicentre phase II trial of the sequencing of Radium-223 and Docetaxel plus prednisone in symptomatic bone-only metastatic castration-resistant prostate cancer (mCRPC)

Open-label, randomized phase II trial in patients with symptomatic bone-only metastatic castration-resistant prostate cancer. Eligible patients are randomly assigned into two arms:

* Arm A: radium-223 initially followed by docetaxel plus prednisone at the time of progression (the second step is optional according to clinical evolution of disease)
* Arm B: docetaxel plus prednisone initially followed by radium-223 at the time of progression (the second step is optional according to clinical evolution of disease).

Randomized, multicentre phase II trial of the sequencing of Radium-223 and Docetaxel plus prednisone in symptomatic bone-only metastatic castration-resistant prostate cancer (mCRPC) Primary objective: To determine the effects of sequential treatment between radium-223 and docetaxel on the percentage of symptomatic bone-only CRPC patients experiencing improvement or worsening in health-related quality of life (HRQoL) Secondary objective: To compare survival in patients treated with sequential therapy between radium-223 and docetaxel and to identify predictive factors of Radium-223 for clinical outcome (progression free survival and overall survival) in this patient population.

Study Treatment:

Radium-223: administered at the dose of 55 kBq per kg body weight, given at 4 week intervals for 6 injections, by slow intravenous injection.

Docetaxel: administered at the dose of 75 mg/m2 by intravenous infusion over a period of 1 hour every 3 weeks for 10 cycles. It is associated with prednisone 5 mg orally twice daily administered continuously.

Statistical methodology A responder analysis investigating treatment effects on percentage of patients experiencing meaningful HRQoL improvement/worsening on treatment will be conducted. When defining meaningful improvement/worsening, the upper limit of the minimally important difference (MID) range will be used. The MIDs for FACT-P total score and subscales that will be used in this study will be 10 and 3, respectively.

Patients experiencing a QoL increase \>=MID from baseline at week 12 will be considered responders while patients experiencing a decrease in HRQoL score \>=MID at this time point will be considered to have experienced worsening HRQoL.

According to primary endpoint, considering a type I error 0.10, type II error 0.20, proportion of responder patients in the standard arm 0.10 and in the experimental arm of 0.40, a total of 70 patients (35 for each arm) will be enrolled in the study. Chi-square tests will be used to test for an association between treatment and meaningful improvement (i.e. responder) or worsening in HRQoL.

According to secondary endpoints, PFS, TPFS and OS will be estimated by the Kaplan-Meier method. The treatment groups will be compared with a two-sided log rank test. All analyses will be done in the intention-to-treat population. For translational studies, we will conduct a prognostic and predictive factor analysis for time-to-event clinical outcomes using a univariate Cox model; significant factors subsequently will be included in a multivariable Cox regression model (cutoff p\<0•05).

Sequencing of Radium-223 and Docetaxel in Symptomatic Bone-only Metastatic Castration-resistant Prostate Cancer

Randomized, Multicentre Phase II Trial of the Sequencing of Radium-223 and Docetaxel Plus Prednisone in Symptomatic Bone-only Metastatic Castration-resistant Prostate Cancer (mCRPC)

HRQoL clinical benefit, according to the Functional Assessment of Cancer Therapy-Prostate (FACT-P)

HRQoL clinical benefit, according to Brief Pain Inventory-Short Form questionnaire (BPI) for bone pain intensity.

PFS defined as the duration of time from randomization to time of progression or death, whichever occurred earlier

TPFS defined as total PFS at the end of the therapeutic sequence

OS defined as the time from randomization to the date of death due to any cause or the last date the patient was known to be alive

evaluation of toxicity by Common Terminology Criteria for Adverse Events (CTCAE) version 4.03

Identification of markers predictive to clinical outcome including:

* translational studies of circulating tumor DNA and/or circulating tumor cells and/or circulating RNA
* serum chromogranin A and neuron specific enolase levels
* positron emission tomography (PET) with choline and/or new tracer

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Sequencing of Radium-223 and Docetaxel in Symptomatic Bone-only Metastatic Castration-resistant Prostate Cancer	NCT03230734	Metastatic Cast...	Radium-223 Docetaxel	18 Years -	Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori
Sequencing of Radium-223 and Docetaxel in Symptomatic Bone-only Metastatic Castration-resistant Prostate Cancer	NCT03230734	Metastatic Cast...	Radium-223 Docetaxel	18 Years -	Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori

Spots Global Cancer Trial Database for bone only metastatic prostate cancer