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)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST S.r.l.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

9 Jun 2017 → 26 Feb 2026

Decision date (initial)

2024-07-29

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

BAYER AG

External identifiers

EU CT number

2024-511660-89-00

EudraCT number

2016-004452-29

ClinicalTrials.gov

NCT03230734

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Safety

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 objectives 1

1. 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

Conditions and MedDRA coding

metastatic castration resistant prostate cancer (mCRPC)

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 15

1. Patients must have histologically or cytologically confirmed adenocarcinoma of prostate
2. Two or more bone metastases confirmed by bone scintigraphy within 8 weeks prior to randomization
3. 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
4. Known castration-resistant disease, defined according to PCWG3 criteria (59) as: castrate serum testosterone level: ≤50 ng/dL (≤1.7 nmol/L)
5. 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
6. 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 scintigraph
7. Patients who failed treatment with any ADT, abiraterone and/or enzalutamide for CRPC that must be terminated at least 4 weeks before C1D1
8. 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
9. Male, aged ≥18 years
10. Life expectancy of greater than 6 months
11. ECOG performance status≤2
12. Patients must have normal organ and marrow function as defined below: leukocytes >3,000/uL, absolute neutrophil count >1,500/uL, platelets >100,000/uL, 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.
13. 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 IRST185.04 - RAPSON Pag. 25 of 83 Eme5.0_24.01.24 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.
14. No evidence (within 5 years) of prior malignancies (except successfully treated basal cell or squamous cell carcinoma of the skin)
15. Participant is willing and able to give informed consent for participation in the study

Exclusion criteria 14

1. Patients who have had radiotherapy within 4 weeks prior to C1D1
2. Patients with known visceral metastases
3. Participation in another clinical trial with any investigational agents within 30 days prior to C1D1
4. 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
5. 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.
6. Patients who received systemic radiotherapy (e.g. samarium, strontium etc.) for the treatment of bone metastases
7. Patients who received blood transfusion or erythropoietin within the last 4 weeks prior to start of study treatment
8. Patients who received prior treatment with Radium-223
9. Patients with malignant lymphadenopathy exceeding 3 cm in short-axis diameter, or symptomatic nodal disease, i.e. scrotal, penile or leg edema
10. 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)
11. 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
12. Patients with imminent or established spinal cord compression based on clinical findings and/or magnetic resonance imaging
13. Positive test for HIV in case of known positivity to human immunodeficiency virus (HIV)
14. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. HRQoL clinical benefit, according to the Functional Assessment of Cancer Therapy–Prostate (FACT-P) and Brief Pain Inventory-Short Form questionnaire (BPI) for bone pain intensity. We will perform HRQoL assessments at baseline, at every cycle of therapy, at EOT visit and during follow up both for Step 1 and 2, ARM A and B.

Secondary endpoints 7

1. Progression-free survival (PFS), defined as the duration of time from randomization to time of progression or death, whichever occurred earlier
2. Total progression-free survival (TPFS), defined as total PFS at the end of the therapeutic sequence
3. Overall survival (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
4. Safety
5. Identification of markers predictive to clinical outcome including: translational studies of circulating tumor DNA and/or circulating tumor cells and/or circulating RNA and/or germ line DNA with the collection of blood samples: at C1D1 for Step 1 and 2 of both arms, before the cycle 4 for Step 1 ARM A and for Step 2 ARM B, before the cycle 5 for the Step 1 ARM B and Step 2 ARM A, at EOT visit and at 3 months of FUPfor Step 1 and 2 of both arms. As an option, it will be possible to require a sa
6. Identification of markers predictive to clinical outcome including: serum chromogranin A and neuron specific enolase levels at C1D1 for Step 1 and 2 of both arms, before the cycle 4 for Step 1 ARM A and for Step 2 ARM B, before the cycle 5 for the Step 1 ARM B and Step 2 ARM A, at EOT visit and at 3 months of FUP for Step 1 and 2 of both arms.
7. Identification of markers predictive to clinical outcome including: PET with choline and/or new tracer (optional): at baseline (See paragraph 5.3), at 4 weeks (±2 weeks) after the C1D1, and at EOT for the Step 1.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST S.r.l.

Sponsor organisation

Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST S.r.l.

Address

Via Piero Maroncelli 40

City

Meldola

Postcode

47014

Country

Italy

Scientific contact point

Organisation

Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST S.r.l.

Contact name

Ugo De Giorgi

Public contact point

Organisation

Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST S.r.l.

Contact name

Oriana Nanni

Locations

1 EU/EEA country · 11 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 12 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications