A large-scale comparative study evaluating an intravenous treatment, cabazitaxel, and radiation therapy to the pelvic lymph nodes in patients with high-risk localized prostate cancer treated with radiotherapy and hormone therapy.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Unicancer

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

6 Dec 2013 → ongoing

Decision date (initial)

2024-11-04

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Sanofi

External identifiers

EU CT number

2024-517622-25-00

EudraCT number

2012-000566-38

ClinicalTrials.gov

NCT01952223

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Therapy, Others

To assess the effect of neoadjuvant cabazitaxel and pelvic radiotherapy in combination with ADT-radiotherapy on clinical progression-free survival in patients with high-risk localized prostate cancer (with a stringent selection of patients with at least 2 high-risk features), in a 2 by 2 factorial trial.

Secondary objectives 11

1. Prostate-specific antigen response at 3 months
2. Biochemical progression-free survival
3. Metastases-free survival
4. Local relapse-free survival
5. Overall survival
6. Prostate cancer-specific survival
7. Acute toxicity
8. Impact of treatment on serum testosterone
9. Long-term toxicity (including toxicity related to radiotherapy)
10. Predictive biomarkers of treatment efficacy
11. Quality of life

Conditions and MedDRA coding

Patients with localized prostate cancer and high-risk features of relapse.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 17

1. Any T histologically confirmed adenocarcinoma of the prostate
2. No clinically or radiologically suspected metastases, including no enlarged pelvic lymph nodes (> 1 cm in small diameter)
3. Gleason score ≥ 6
4. Meets at least 2 of the following criteria for high-risk: - Gleason score ≥ 8 - T3 or T4 disease (T3 defined by MRI is acceptable) - Prostate-specific antigen equal or greater than 20 ng/mL
5. No prior treatment for prostate cancer except lymph node dissection (patients with pN- and pN+ disease can be accrued) or ADT (started up to 6 weeks before randomization).
6. 18 years ≤ Age≤ 75 years
7. ECOG 0-1 performance status
8. Expected life expectancy of more than 10 years
9. Absolute neutrophil count ≥ 1.5 x 10^9/L
10. Platelets ≥ 100 x 10^9/L
11. Hb≥ 9.0 g/dL
12. Hepatic function: serum bilirubin ≤ 1 ULN (except in case of Gilbert's syndrome) ; AST and ALT ≤ 2.5 x ULN
13. Renal function (creatinine clearance using the CKD-EPI formula (Chronic Kidney Disease Epidemiology group, see Appendix 4) ≥ 60 mL/min).
14. Potentially reproductive patients must agree to use an effective contraceptive method while on treatment and for 6 months after the final dose of investigational product.
15. Patient must be affiliated to a Social Security System or should fulfill the country legislation for clinical trials.
16. Patient who have received the information sheet and signed the informed consent form.
17. Patient must be willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures

Exclusion criteria 11

1. Patient with other known concurrent severe and/or uncontrolled medical disease which could compromise participation in the study, such as: a- infection, b- cardiac disease such as uncontrolled hypertension, congestive cardiac failure, ventricular arrhythmias, active ischemic heart disease, myocardial infarction within one year, LVEF > grade 2, c- uncontrolled diabetes mellitus, d- current active hepatic or biliary disease (with exception of subjects with Gilbert's syndrome, asymptomatic gallstones, stable chronic liver disease per investigator assessment), e- renal disease, f- active GI tract ulceration, malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel. Subjects with active, uncontrolled ulcerative colitis are also excluded, g- known severely impaired lung function (spirometry and DLCO 70% or less of normal and O2 saturation of 88% or less at rest on room air).
2. Other prior malignancy within the last 5 years, except basal cell skin cancer
3. Physical or psychological condition that would preclude study compliance
4. Hypersensitivity to cabazitaxel (hypersensitivity reaction ≥grade 3), to other taxanes, or to any excipients of the formulation including polysorbate 80
5. Patient with significantly altered mental status prohibiting the understanding of the study or with psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.
6. Patient who received any other investigational drugs within the 30 days prior to the start of cabazitaxel.
7. Previous pelvic irradiation that make prostatic irradiation impossible
8. Severe GI disorders precluding pelvic irradiation
9. Patient already included in another therapeutic trial involving an experimental drug
10. Individual deprived of liberty or placed under the authority of a tutor.
11. Concomitant prohibited treatment. Concurrent or planned treatment with strong inhibitors or strong inducers of cytochrome P450 3A4/5. A one week wash-out period is necessary for patients who are already on these treatments.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. La supervivencia específica del cáncer de próstata se calculará entre la fecha de aleatorización y la fecha de la muerte por el cáncer de próstata.

Secondary endpoints 11

1. The prostate-specific antigen response at 3 months will be defined as a serum PSA value (≤ 0.2 ng/mL)
2. The biochemical progression-free survival is defined as the time from randomization to the date of PSA relapse (evaluated according to Phoenix criteria i.e. nadir + 2 ng/mL) or death.
3. The metastases-free survival is defined as the time from randomization to the date of the appearance of the metastases on imaging (mainly bone scan and CT-scan) or death.
4. The local relapse-free survival is defined as the time from randomization to the date of the appearance of the first local relapse or death.
5. The overall survival will be calculated from the date of randomization to the date of death from any cause or date of the last follow-up.
6. The prostate cancer-specific survival will be calculated from the date of randomization to the date of the death due to prostate cancer
7. The acute toxicity (i.e. during the treatment period), will be evaluated according to the NCI-CTC v4.0 criteria
8. The impact of treatment on serum testosterone will be evaluated at baseline, 6 months then yearly.
9. The long-term toxicity (potency, cardiac, hot flashes and late toxicity related to radiotherapy or chemotherapy) will be evaluated at 1 year, 2 years and 5 years. The toxicity related to the radiotherapy will be assessed using NCI-CTC v4.0 criteria.
10. The predictive biomarkers of treatment efficacy will be assessed on archival biopsy specimens
11. The quality of life will be evaluated with the QLQ –C30 and PR25 questionnaires at baseline, 6 months then yearly up to 10 years after the randomization date.

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Unicancer

Sponsor organisation

Unicancer

Address

101 Rue De Tolbiac

City

Paris

Postcode

75013

Country

France

Scientific contact point

Organisation

Unicancer

Contact name

Nourredine AIT RAHMOUNE

Public contact point

Organisation

Unicancer

Contact name

Nourredine AIT RAHMOUNE

Locations

3 EU/EEA countries · 61 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 10 files

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

Application history

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