Darotaxel

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male

Therapeutic area

Diseases [C] - Male Urogenital Diseases [C12]

Trial duration

28 Oct 2024 → ongoing

Decision date (initial)

2024-10-28

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-516939-28-00

EudraCT number

2022-003792-41

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To compare progression free survival (PFS) between treatment with docetaxel or cabazitaxel and darolutamide versus treatment with docetaxel or cabazitaxel in mCRPC patients.

Secondary objectives 9

1. To compare overall survival between treatment with docetaxel or cabazitaxel and darolutamide versus treatment with docetaxel or cabazitaxel in mCRPC patients.
2. To compare time to progression, defined as time from randomization to radiologic, biochemical or pain progression, whichever occurs first, between treatment with docetaxel or cabazitaxel and darolutamide versus treatment with docetaxel or cabazitaxel in mCRPC patients.
3. To compare the time to PSA progression between treatment with docetaxel or cabazitaxel and darolutamide versus treatment with docetaxel or cabazitaxel in mCRPC patients.
4. To compare the time to pain progression between treatment with cabazitaxel and darolutamide versus treatment with cabazitaxel in mCRPC patients.
5. To evaluate the safety of treatment with docetaxel or cabazitaxel and darolutamide in mCRPC patients.
6. To investigate the relationship between tumour hallmarks at baseline and treatment response
7. To investigate alterations in tumour hallmarks between different timepoints
8. To investigate the predictive value of potential response markers
9. To investigate the effect of taxanes on immune cell populations and to investigate the relationship between immune cell populations and treatment response.

Conditions and MedDRA coding

metastatic castration-resistant prostate cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Age ≥ 18 years;
2. A confirmed diagnosis of progressive mCRPC (progression according to Prostate cancer Working Group (PCWG) 3 criteria), with an indication for docetaxel or cabazitaxel. Progression defined as ≥ 1 of the following 3 criteria: a. Radiographic disease progression in soft tissue per RECIST v1.1 b. Radiographic disease progression in bone defined by the appearance of ≥ 2 new bone lesions on bone scan. c. PSA progression defined as ≥ 2 sequential rises in PSA obtained ≥ 1 week apart with a minimal starting value of ≥ 1 ng/mL. A PSA value ≥ 2 ng/mL is required at study entry.
3. Patients should have had disease progression previously on at least one ARSi (abiraterone, apalutamide, darolutamide or enzalutamide). ARSi administration is allowed both in the mCNPC and in the mCRPC setting. Coadministration of docetaxel in mCNPC (triplet-therapy) is allowed.
4. WHO performance ≤ 2 (see appendix A)
5. Able and willing to sign the Informed Consent Form prior to screening evaluations
6. Adequate haematological, renal and liver function and chemistry, defined as: a. Hemoglobin ≥ 6.0 mmol/L b. Platelets ≥ 100 x 109/L c. ALT/AST ≤ 3x ULN and ≤ 5x ULN in case of liver metastases d. Creatinine clearance ≥ 50 ml/min e. Serum testosterone ≤ 1.7 nmol/L

Exclusion criteria 5

1. Impossibility or unwillingness to take oral drugs
2. Hypersensitivity to taxanes
3. Known serious illness or medical unstable conditions that could interfere with this study requiring treatment (e.g. HIV, hepatitis, Varicella zoster or herpes zoster, organ transplants, kidney failure, serious liver disease (e.g. severe cirrhosis), cardiac and respiratory diseases)
4. Symptomatic peripheral neuropathy CTCAE grade ≥2
5. Docetaxel-rechallenge.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The main study endpoint is progression free survival, which is defined as time from randomization to radiologic, biochemical or pain progression or death from any cause, whichever occurs first, according to PCWG3 (Appendix C).

Secondary endpoints 8

1. Overall survival, defined as time from randomization to death from any cause.
2. Time to progression, defined as time from randomization to radiologic, biochemical or pain progression, whichever occurs first.
3. The time to PSA progression, defined as time from randomization to biochemical progression.
4. The time to pain progression, defined as time from randomization to pain progression.
5. The number and severity of adverse events
6. Cell-free DNA aneuploidy scores and somatic aberrations in circulating tumor DNA
7. Differential expression of relevant genes, as measured in tissue and liquid biopsies. (comparing tissue and liquid biopsies at baseline and on-treatmen
8. Immune subset phenotyping and subtyping as measured in tissue and whole blood

Investigational products

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

Test 1

Comparator 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Sponsor organisation

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Address

Dr. Molewaterplein 40

City

Rotterdam

Postcode

3015 GD

Country

Netherlands

Scientific contact point

Organisation

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Contact name

Prof. R.H.J. Mathijssen

Public contact point

Organisation

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Contact name

Prof. R.H.J. Mathijssen

Locations

1 EU/EEA country · 18 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 15 files

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

Application history

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