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Metastatic Castration-resistant Prostate CancerPhase 2RAPSONNCT03230734

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

A Phase 2 study testing Radium-223 and Docetaxel in people with Metastatic Castration-resistant Prostate Cancer, run by Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS at 15 sites in Italy.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older, men only
What is being tested?
Radium-223 and Docetaxel
Could I receive a placebo?
No, everyone receives an active treatment
How many people
70 participants
Where
15 sitesItaly
Study dates
1 Sep 2017to Jul 2025
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 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients must have histologically or cytologically confirmed adenocarcinoma of prostate
  • Two or more bone metastases confirmed by bone scintigraphy within 8 weeks prior to randomization
  • Symptomatic disease defined as regular use of opioid or nonopioid analgesic medication or treatment with external beam radiation therapy within the previous 12 weeks for cancer-related bone pain
  • Known castration-resistant disease, defined according to PCWG3 criteria (59) as: castrate serum testosterone level: ≤50 ng/dL (≤1.7 nmol/L)
  • Subjects who have failed initial hormonal therapy, either by orchiectomy or by using a GnRH agonist in combination with an anti-androgen, must first progress through antiandrogen withdrawal prior to being eligible. The minimum timeframe to document failure of anti-androgen withdrawal will be four weeks
  • Progressive disease based on PSA and/or radiographic PCWG3 criteria:
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  • Serum PSA progression defined as two consecutive increases in PSA over a previous reference value within 6 months of first study treatment, each measurement at least one week apart. Serum PSA at screening ≥ 1ng/mL is the minimal starting value b. or radiographic disease progression based on documented bone lesions by the appearance of two or more new lesions by bone scintigraphy.
  • Patients who failed treatment with any ADT, abiraterone and/or enzalutamide for CRPC that must be terminated at least 4 weeks beforeC1D1.
  • Patients who received prior docetaxel for hormone-naïve prostate cancer should only be allowed if more than 2 years have been between the last administration of docetaxel and C1D1.
  • Male, aged ≥18 years
  • Life expectancy of greater than 6 months
  • ECOG performance status≤2 (see Appendix A)
  • Patients must have normal organ and marrow function as defined below:
  • leukocytes \> 3,000/µL
  • absolute neutrophil count \>1,500/µL
  • platelets \>100,000/µL
  • total bilirubin within normal institutional limits
  • AST(SGOT)/ALT(SGPT) \<2.5 X institutional upper limit of normal
  • creatinine within normal institutional limits In the presence of borderline values, the participating Centers will be able to discuss individual cases with the Coordinating Center.
  • Male patient and his female partner who is of childbearing potential must use 2 acceptable methods of birth control (1 of which must include a condom as a barrier method of contraception) starting at screening and continuing throughout the study period and for 6 months after the last dose of radium-223 or docetaxel, according to guideline "Recommendation related to contraception and pregnancy testing in clinical trials", (2020_09) (See Appendix F). Two acceptable methods of birth control thus include condom (barrier method of contraception) and one of the following is required (established use of oral, or injected or implanted hormonal method of contraception by the female partner; placement of an intrauterine device (IUD) or intrauterine system (IUS) by the female partner; additional barrier method like occlusive cap with spermicidal foam/gel/film/cream/suppository in the female partner; tubal ligation in the female partner; vasectomy or other procedure resulting in infertility (eg, bilateral orchiectomy), for more than 6 months.
  • No evidence (within 5 years) of prior malignancies (except successfully treated basal cell or squamous cell carcinoma of the skin).
  • Participant is willing and able to give informed consent for participation in the study.

Who cannot join

  • Patients who have had radiotherapy within 4 weeks prior to C1D1.
  • Patients with known visceral metastases
  • Participation in another clinical trial with any investigational agents within 30 days prior to C1D1.
  • Concurrent use of other anticancer agents or treatments, with the following exceptions: LHRH agonists or antagonists, denosumab or bisphosphonate (eg, zoledronic acid). Ongoing treatment should be kept at a stable schedule; however, if medically required, a change of dose, compound, or both is allowed.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Patients who received systemic radiotherapy (e.g. samarium, strontium etc.) for the treatment of bone metastases.
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  • Patients who received blood transfusion or erythropoietin within the last 4 weeks prior to start of study treatment.
  • Patients who received prior treatment with Radium-223.
  • Patients with malignant lymphadenopathy exceeding 3 cm in short-axis diameter, or symptomatic nodal disease, i.e. scrotal, penile or leg edema.
  • Other primary tumor (other than CRPC) including hematological malignancy present within the last 5 years (except non-melanoma skin cancer or low-grade superficial bladder cancer).
  • Maintenance treatment with corticosteroids corresponding to a prednisolone or prednisone dose above 10 mg/day. The dose must have been stable for at least 5 days.
  • Patients with imminent or established spinal cord compression based on clinical findings and/or magnetic resonance imaging.
  • Positive test for HIV in case of known positivity to human immunodeficiency virus (HIV).
  • Patients with active hepatitis B (defined as having a positive hepatitis B surface antigen[HBsAg] test at screening) or hepatitis C Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as having a negative HBsAg test and a positive antibody to hepatitis B core antigen [anti-HBc] antibody test) are eligible.
  • Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA.

Trial locations and contacts

15 sites in 1 country.

15 sites in 1 country

Italy15 sites

  • UO Oncologia medica, IRCCS Centro di Riferimento Oncologico di Aviano

    Aviano

  • IO Oncologia Medica, Ospedale Regionale Bolzano - Az. Sanitaria Alto Adige

    Bolzano

  • IRCCS Ospedale Policlinico San Martino

    Genova

  • U.O. Oncologia PO Vito Fazzi

    Lecce, LE, 73100

  • UO Oncologia Medica, IRST IRCCS

    Meldola, FC, 47014

  • Istituto Europeo di Oncologia

    Milan

  • INT di Napoli Fondazione "G. Pascale"

    Naples

  • Ospedale Sacro Cuore "Don Calabria"

    Negrar, VR

  • Oncologia Medica San Luigi Gonzaga

    Orbassano, TO, 10043

  • UO Oncologia Medica, Azienda Ospedaliera-Universitaria di Parma

    Parma

  • UO Oncologia Medica, AOU PISANA - Ospedale Santa Chiara

    Pisa

  • Azienda Ospedaliera Arcispedale S. Maria Nuova/IRCCA di Reggio Emilia

    Reggio Emilia

  • UO Oncologia Medica, C.R.O.B. - I.R.C.C.S

    Rionero in Vulture, PZ

  • IRCCS Istituto Clinico Humanitas

    Rozzano, Milano, 20089

  • Ospedale S. Chiara - UO Oncologia Medica

    Trento, TN, 38122

Other trials in Italy

About this study

Official title: 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)

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).
Read the detailed description

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).

Being tested
Radium-223, Docetaxel
Keywords
prostate cancer, castration-resistant prostate cancer, metastatic prostate cancer, bone only metastatic prostate cancer, radium-223, Docetaxel
Medical subject headings
Prostatic Neoplasms

What participants receive

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

  • Radium-223Drug

    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

  • DocetaxelDrug

    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.

Study groups in NCT03230734
Study groupRoleWhat they receive
Treatment Arm AExperimentalradium-223 initially followed by docetaxel plus prednisone at the time of progression (PD)
Receives: Drug: Radium-223; Drug: Docetaxel
Treatment Arm BExperimentaldocetaxel plus prednisone initially followed by radium-223 at the time of progression (PD)
Receives: Drug: Radium-223; Drug: Docetaxel

What is being measured

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

  1. health-related quality of life (HRQoL) clinical benefit

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

    Measured: up to 36 months

  2. health-related quality of life (HRQoL ) clinical benefit

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

    Measured: up to 36 months

Secondary outcomes (5)

  1. Progression-free survival (PFS)

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

    Measured: up to 36 months

  2. Total progression-free survival (TPFS)

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

    Measured: up to 36 months

  3. Overall survival (OS)

    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

    Measured: up to 36 months

  4. toxic effects categorization for safety monitoring

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

    Measured: up to 36 months

  5. Identification of markers predictive to clinical outcome

    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

    Measured: up to 36 months

Timeline

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

  1. First posted26 Jul 2017
  2. Study start1 Sep 2017
  3. Primary completionJul 2025 (estimated)
  4. Study completionJul 2025 (estimated)

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
Randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
70 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03230734
Sponsor's protocol ID
IRST185.04
Other IDs
2016-004452-29, 2016
Acronym
RAPSON
Status last verified
Sep 2024
First submitted
24 Jul 2017
Last updated
27 Sep 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Radium-223 and Docetaxel in people with Metastatic Castration-resistant Prostate Cancer, run by Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS at 15 sites 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 22 inclusion and 15 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: status not confirmed, as of the sponsor's last update on 27 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites 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?

Results are not available in the source record.

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?

health-related quality of life (HRQoL) clinical benefit (time frame: up to 36 months). The study lists 2 primary outcomes in all. 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 NCT03230734.

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 27 Sep 2024.

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