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

NCT03230734 | Active Not Recruiting Phase 2

• 2 other identifiers: IRST185.042016-004452-29
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 15

Brief 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. 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).

Conditions

Metastatic Castration-resistant Prostate Cancer

Keywords

prostate cancer; castration-resistant prostate cancer; metastatic prostate cancer; bone only metastatic prostate cancer; radium-223; Docetaxel

Outcome Measures

Primary Outcomes (2)

• health-related quality of life (HRQoL) clinical benefit

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

  up to 36 months

• health-related quality of life (HRQoL ) clinical benefit

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

  up to 36 months

Secondary Outcomes (5)

• Progression-free survival (PFS)

  up to 36 months

• Total progression-free survival (TPFS)

  up to 36 months

• Overall survival (OS)

  up to 36 months

• toxic effects categorization for safety monitoring

  up to 36 months

• Identification of markers predictive to clinical outcome

  up to 36 months

Study Arms (2)

Treatment Arm A

EXPERIMENTAL

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

Drug: Radium-223; Drug: Docetaxel

Treatment Arm B

EXPERIMENTAL

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

Drug: Radium-223; Drug: Docetaxel

Interventions

Radium-223 DRUG

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

Treatment Arm A; Treatment Arm B

Docetaxel DRUG

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.

Treatment Arm A; Treatment Arm B

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• a. 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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS: lead
• Bayer: collaborator

Study Sites (15)

UO Oncologia Medica, IRST IRCCS

Meldola, FC, 47014, Italy

Location

U.O. Oncologia PO Vito Fazzi

Lecce, LE, 73100, Italy

Location

IRCCS Istituto Clinico Humanitas

Rozzano, Milano, 20089, Italy

Location

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

Rionero in Vulture, PZ, Italy

Location

Ospedale S. Chiara - UO Oncologia Medica

Trento, TN, 38122, Italy

Location

Oncologia Medica San Luigi Gonzaga

Orbassano, TO, 10043, Italy

Location

Ospedale Sacro Cuore "Don Calabria"

Negrar, VR, Italy

Location

UO Oncologia medica, IRCCS Centro di Riferimento Oncologico di Aviano

Aviano, Italy

Location

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

Bolzano, Italy

Location

IRCCS Ospedale Policlinico San Martino

Genova, Italy

Location

Istituto Europeo di Oncologia

Milan, Italy

Location

INT di Napoli Fondazione "G. Pascale"

Napoli, Italy

Location

UO Oncologia Medica, Azienda Ospedaliera-Universitaria di Parma

Parma, Italy

Location

UO Oncologia Medica, AOU PISANA - Ospedale Santa Chiara

Pisa, Italy

Location

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

Reggio Emilia, Italy

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Radium-223; Docetaxel

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)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Ugo De Giorgi, MD

  Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Via Maroncelli 40, 47014 Meldola, ITALY

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 24, 2017
• First Posted: July 26, 2017
• Study Start: September 1, 2017
• Primary Completion: July 1, 2025
• Study Completion: July 1, 2025
• Last Updated: September 27, 2024

Record last verified: 2024-09

Locations

IT (15)