Clinical trial NCT04423913: Safety, Tolerability, Distribution & Dose Effect of Neoadjuvant Transarterial Chemoembolization With Doxorubicin in Prostate Cancer Patients Before Radical Prostatectomy
Official title: Evaluation of the Safety, Tolerability, Distribution and Dose Effect of Neoadjuvant Transarterial Chemoembolization With Doxorubicin in Prostate Cancer Patients at a High Risk of Recurrence Before Radical Prostatectomy: A Phase IIa Study
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Prostate Cancer
Keywords: doxorubicin
beads
embolization
chemoembolization
prostate cancer
Lead sponsor: Centre Hospitalier Universitaire de Nīmes
Sponsor class: OTHER
First posted: 2020-06-09
Enrollment: 12
Sex: MALE
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: This is a purely descriptive, non randomized, non controlled, prospective sequential-type pilot study on the first use in the indication for prostatic arterial embolization using beads loaded with doxorubicin in increasing doses: 0 mg, 2.5mg, 5 mg and 10 mg. It is a study with escalating doses of doxorubicin : 3 patients with non-loaded beads, 3 patients with beads loaded at 2.5 mg (1/20 of the dose administered for liver tumors), 3 patients with beads loaded at 5mg and 3 patients with beads loaded at 10mg.
Primary purpose: TREATMENT

Brief summary: Our hypothesis is that the doxorubicin eluting-beads currently used in hepato-oncology might be applicable to high-grade prostate cancer before radical prostatectomy.

The primary objective of this Phase IIa pilot study is to evaluate the safety of performing prostate embolization with doxorubicin eluting-beads according to different loading doses. Four dose levels will be tested: doxorubicin-free beads to test the effect of embolization alone, 2.5 mg of doxorubicin (1/20 of the dose administered for liver cancers), 5 mg and 10 mg of doxorubicin.

The secondary objectives of the study are to evaluate the tolerance (functionnal questionaries at D0, D14 M1 and M3; collection of complications at D1, D5, D14, M1, M3; MRI at D14), evaluate the systemic diffusion of doxorubicin (doxorubinemia at D1), evaluate an early anti-tumor effect of the treatment (via a prostate-specific antigen test at D14 M1, M3 and magnetic resonance imaging at D14), describe the distribution of beads observed on the surgical specimen and evaluate the dose effect at 1 month and 3 months after surgery (via a prostate-specific antigen test at D14, M1, M3 and magnetic resonance imaging at D14).


Eligibility criteria: Inclusion Criteria:

* Patients must have given written informed consent.
* Patients must be affiliated to or benefit from a health insurance scheme.
* Patients with a high-risk prostate cancer with a Gleason score of 9-10 on the biopsy, candidate for a multimodal treatment with radical prostatectomy validated at the multidisciplinary meeting.
* Patients with a normal blood count.
* Patients with a normal liver function test.
* Patients with an electrocardiogram including left ventricle ejection fraction (ventricular scintigraphy or echocardiography) and an echocardiogram allowing us to rule out heart disease.
* Patient must be completely recovered from acute toxicities (such as stomatitis, neutropenia, thrombopenia and generalized infections) caused by a previous cytotoxic treatment.
* OMS/ECOG score≤1 (to guard against a possible loss of therapeutic opportunity related to a delay in surgery caused by chemo-embolization).

Exclusion Criteria:

* Patients who are taking part in another study.
* Patients in an exclusion period determined by a previous study.
* Patients under legal guardianship, curatorship or tutorship.
* Patients not in condition to be able to express his consent (e.g. patient undergoing psychiatric treatment with mental disorders)
* Patients who refuse to sign the consent form.
* Patients for whom it is impossible to give clear information. • Patient already has a metastatic disease.
* Patients who have contraindications for surgery.
* Patients with a rectal or vesicular collateral pathology that cannot be excluded or a collateral penile pathology which, by precaution, would not allow embolization (unknown effect on the erection in the event of arterial exclusion).
* Patients with a contraindication for magnetic resonance imaging (pacemaker incompatible with MRI, claustrophobia, metal apparatus, total hip prosthesis).
* Patients with a past history of aortobifemoral bypass procedure or other vascular surgery making endovascular access to the prostate arteries impossible.
* Patients with irreversible hemostasis disorder: TP \< 50%, TCA \> twice the control, Platelets \< 60 G/L.
* Patients with contraindications as mentioned in the Summary of Product Characteristics for Doxorubicin.

Primary outcomes:
measure: Evaluation of safety of prostate embolization using unloaded beads.
timeFrame: Day 0 (i.e. on the day of the intervention)
measure: Evaluation of safety of prostate embolization using unloaded beads.
timeFrame: Day 1 (i.e. one day after the intervention)
measure: Evaluation of safety of prostate embolization using unloaded beads.
timeFrame: Day 5 (i.e. 5 days after the intervention)
measure: Evaluation of safety of prostate embolization using unloaded beads.
timeFrame: Day 14 (i.e. 2 weeks after the intervention)
measure: Evaluation of safety of prostate embolization using unloaded beads.
timeFrame: Day 30 (i.e. 1 month after the intervention)
measure: Evaluation of safety of prostate embolization using unloaded beads.
timeFrame: Three months after the intervention
measure: Evaluation of safety of prostate embolization using beads loaded with 2.5 mg of doxorubicin
timeFrame: Day 0 (i.e. on the day of the intervention)
measure: Evaluation of safety of prostate embolization using beads loaded with 2.5 mg of doxorubicin
timeFrame: Day 1 (i.e. one day after the intervention)
measure: Evaluation of safety of prostate embolization using beads loaded with 2.5 mg of doxorubicin
timeFrame: Day 5 (i.e. 5 days after the intervention)
measure: Evaluation of safety of prostate embolization using beads loaded with 2.5 mg of doxorubicin
timeFrame: Day 14 (i.e. 2 weeks after the intervention)
measure: Evaluation of safety of prostate embolization using beads loaded with 2.5 mg of doxorubicin
timeFrame: Day 30 (i.e. 1 month after the intervention)
measure: Evaluation of safety of prostate embolization using beads loaded with 2.5 mg of doxorubicin
timeFrame: Three months after the intervention
measure: Evaluation of safety of prostate embolization using beads loaded with 5.0 mg of doxorubicin
timeFrame: Day 0 (i.e. on the day of the intervention)
measure: Evaluation of safety of prostate embolization using beads loaded with 5.0 mg of doxorubicin
timeFrame: Day 1 (i.e. one day after the intervention)
measure: Evaluation of safety of prostate embolization using beads loaded with 5.0 mg of doxorubicin
timeFrame: Day 5 (i.e. 5 days after the intervention)
measure: Evaluation of safety of prostate embolization using beads loaded with 5.0 mg of doxorubicin
timeFrame: Day 14 (i.e. 2 weeks after the intervention)
measure: Evaluation of safety of prostate embolization using beads loaded with 5.0 mg of doxorubicin
timeFrame: Day 30 (i.e. 1 month after the intervention)
measure: Evaluation of safety of prostate embolization using beads loaded with 5.0 mg of doxorubicin
timeFrame: 3 months after the intervention
measure: Evaluation of safety of prostate embolization using beads loaded with 10.0 mg of doxorubicin
timeFrame: Day 0 (i.e. on the day of the intervention)
measure: Evaluation of safety of prostate embolization using beads loaded with 10.0 mg of doxorubicin
timeFrame: Day 1 (i.e. one day after the intervention)
measure: Evaluation of safety of prostate embolization using beads loaded with 10.0 mg of doxorubicin
timeFrame: Day 5 (i.e. 5 days after the intervention)
measure: Evaluation of safety of prostate embolization using beads loaded with 10.0 mg of doxorubicin
timeFrame: Day 14 (i.e. 2 weeks after the intervention)
measure: Evaluation of safety of prostate embolization using beads loaded with 10.0 mg of doxorubicin
timeFrame: Day 30 (i.e. 1 month after the intervention)
measure: Evaluation of safety of prostate embolization using beads loaded with 10.0 mg of doxorubicin
timeFrame: Three months after the intervention
Secondary outcomes:
measure: Tolerance of prostate embolization using unloaded beads.
timeFrame: Day 14
measure: Tolerance of prostate embolization using beads loaded with 2.5 mg of doxorubicin.
timeFrame: Day 14
measure: Tolerance of prostate embolization using beads loaded with 5.0 mg of doxorubicin.
timeFrame: Day 14
measure: Tolerance of prostate embolization using beads loaded with 10.0 mg of doxorubicin.
timeFrame: Day 14
measure: Tolerance of prostate embolization using unloaded beads: Clavien-Dindo score
timeFrame: Day 14
measure: Tolerance of prostate embolization using beads loaded with 2.5 mg of doxorubicin:Clavien-Dindo score
timeFrame: Day 14
measure: Tolerance of prostate embolization using beads loaded with 5.0 mg of doxorubicin: Clavien-Dindo score
timeFrame: Day 14
measure: Tolerance of prostate embolization using beads loaded with 10.0 mg of doxorubicin: Clavien-Dindo score
timeFrame: Day 14
measure: Tolerance of prostate embolization using unloaded beads : International Prostate Symptom Score
timeFrame: Day 14
measure: Tolerance of prostate embolization using unloaded beads : International Prostate Symptom Score
timeFrame: Day 30 (i.e. one month after embolization)
measure: Tolerance of prostate embolization using unloaded beads : International Prostate Symptom Score
timeFrame: Three months after embolization
measure: Evaluation of tolerance of prostate embolization using beads loaded with 2.5 mg of doxorubicin : International Prostate Symptom Score
timeFrame: Day 14
measure: Evaluation of tolerance of prostate embolization using beads loaded with 2.5 mg of doxorubicin : International Prostate Symptom Score
timeFrame: Day 30 (i.e. 1 month after embolization)
measure: Evaluation of tolerance of prostate embolization using beads loaded with 2.5 mg of doxorubicin : International Prostate Symptom Score
timeFrame: Three months after embolization
measure: Tolerance of prostate embolization using beads loaded with 5.0 mg of doxorubicin : International Prostate Symptom Score
timeFrame: Day 14
measure: Tolerance of prostate embolization using beads loaded with 5.0 mg of doxorubicin : International Prostate Symptom Score
timeFrame: Day 30 i.e. 1 month after embolization
measure: Tolerance of prostate embolization using beads loaded with 5.0 mg of doxorubicin : International Prostate Symptom Score
timeFrame: Three months after embolization
measure: Tolerance of prostate embolization using beads loaded with 10.0 mg of doxorubicin : International Prostate Symptom Score
timeFrame: Day 14
measure: Tolerance of prostate embolization using beads loaded with 10.0 mg of doxorubicin : International Prostate Symptom Score
timeFrame: Day 30 (i.e. 1 month after embolization)
measure: Tolerance of prostate embolization using beads loaded with 10.0 mg of doxorubicin : International Prostate Symptom Score
timeFrame: Three months after embolization
measure: Tolerance of prostate embolization using unloaded beads : IIEF-6 score
timeFrame: Day 14
measure: Tolerance of prostate embolization using unloaded beads : IIEF-6 score
timeFrame: Day 30 (i.e. 1 month after embolization)
measure: Tolerance of prostate embolization using unloaded beads : IIEF-6 score
timeFrame: Three months after embolization
measure: Tolerance of prostate embolization using beads loaded with 2.5 mg of doxorubicin: IIEF-6 score
timeFrame: Day 14
measure: Tolerance of prostate embolization using beads loaded with 2.5 mg of doxorubicin: IIEF-6 score
timeFrame: Day 30 (i.e. one month after embolization)
measure: Tolerance of prostate embolization using beads loaded with 2.5 mg of doxorubicin: IIEF-6 score
timeFrame: Three months after embolization)
measure: Tolerance of prostate embolization using beads loaded with 5.0 mg of doxorubicin: IIEF-6 score
timeFrame: Day 14
measure: Tolerance of prostate embolization using beads loaded with 5.0 mg of doxorubicin: IIEF-6 score
timeFrame: Day 30 (i.e. 1 month after embolization)
measure: Tolerance of prostate embolization using beads loaded with 5.0 mg of doxorubicin: IIEF-6 score
timeFrame: Three months after embolization
measure: Tolerance of prostate embolization using beads loaded with 10.0 mg of doxorubicin: IIEF-6 score
timeFrame: Day 14
measure: Tolerance of prostate embolization using beads loaded with 10.0 mg of doxorubicin: IIEF-6 score
timeFrame: Day 30 (i.e.1 month after embolization)
measure: Tolerance of prostate embolization using beads loaded with 10.0 mg of doxorubicin: IIEF-6 score
timeFrame: Three months after embolization
measure: Tolerance of prostate embolization using unloaded beads : EORTC - QLQ-C30 score
timeFrame: Day 14
measure: Tolerance of prostate embolization using unloaded beads : EORTC - QLQ-C30 score
timeFrame: Day 30 (i.e. 1 month after embolization)
measure: Tolerance of prostate embolization using unloaded beads : EORTC - QLQ-C30 score
timeFrame: Three months after embolization
measure: Tolerance of prostate embolization using beads loaded with 2.5 mg of doxorubicin : EORTC - QLQ-C30 score
timeFrame: Day 14
measure: Tolerance of prostate embolization using beads loaded with 2.5 mg of doxorubicin : EORTC - QLQ-C30 score
timeFrame: Day 30 (i.e. 1 month after embolization)
measure: Tolerance of prostate embolization using beads loaded with 2.5 mg of doxorubicin : EORTC - QLQ-C30 score
timeFrame: Three months after embolization
measure: Tolerance of prostate embolization using beads loaded with 5.0 mg of doxorubicin : EORTC - QLQ-C30 score
timeFrame: Day 14
measure: Tolerance of prostate embolization using beads loaded with 5.0 mg of doxorubicin : EORTC - QLQ-C30 score
timeFrame: Day 30 (i.e. 1 month after embolization)
measure: Tolerance of prostate embolization using beads loaded with 5.0 mg of doxorubicin : EORTC - QLQ-C30 score
timeFrame: Three months after embolization
measure: Tolerance of prostate embolization using beads loaded with 10.0 mg of doxorubicin : EORTC - QLQ-C30 score
timeFrame: Day 14
measure: Tolerance of prostate embolization using beads loaded with 10.0 mg of doxorubicin : EORTC - QLQ-C30 score
timeFrame: Day 30 (i.e. 1 month after embolization)
measure: Tolerance of prostate embolization using beads loaded with 10.0 mg of doxorubicin : EORTC - QLQ-C30 score
timeFrame: Three months after embolization
measure: Tolerance of prostate embolization using unloaded beads : 24h pad test
timeFrame: Day 14
measure: Tolerance of prostate embolization using unloaded beads : 24h pad test
timeFrame: Day 30 (i.e. 1 month after embolization)
measure: Tolerance of prostate embolization using unloaded beads : 24h pad test
timeFrame: Three months after embolization
measure: Tolerance of prostate embolization using beads loaded with 2.5 mg of doxorubicine : 24h pad-test
timeFrame: Day 14
measure: Tolerance of prostate embolization using beads loaded with 2.5 mg of doxorubicine : 24h pad-test
timeFrame: Day 30 (1 month after embolization)
measure: Tolerance of prostate embolization using beads loaded with 2.5 mg of doxorubicine : 24h pad-test
timeFrame: Three months after embolization)
measure: Tolerance of prostate embolization using beads loaded with 5.0 mg of doxorubicine : 24h pad test
timeFrame: Day 14
measure: Tolerance of prostate embolization using beads loaded with 5.0 mg of doxorubicine : 24h pad test
timeFrame: Day 30 (i.e. 1 month after embolization)
measure: Tolerance of prostate embolization using beads loaded with 5.0 mg of doxorubicine : 24h pad test
timeFrame: Three months after embolization
measure: Tolerance of prostate embolization using beads loaded with 10.0 mg of doxorubicine : 24h pad test
timeFrame: Day 14
measure: Tolerance of prostate embolization using beads loaded with 10.0 mg of doxorubicine : 24h pad test
timeFrame: Day 30 (1 month after embolization)
measure: Tolerance of prostate embolization using beads loaded with 10.0 mg of doxorubicine : 24h pad test
timeFrame: Three months after embolization
measure: Prostate-specific antigen level in patients treated with unloaded beads.
timeFrame: Day 14 before surgery
measure: Prostate-specific antigen level in patients treated with unloaded beads.
timeFrame: Day 30 (i.e. 1 month after embolization)
measure: Prostate-specific antigen level in patients treated with unloaded beads.
timeFrame: Three months after embolization
measure: Prostate-specific antigen level in patients treated with beads loaded with 2.5 mg of doxorubicine .
timeFrame: Day 14 before surgery
measure: Prostate-specific antigen level in patients treated with beads loaded with 2.5 mg of doxorubicine .
timeFrame: Day 30 (i.e. 1 month after embolization)
measure: Prostate-specific antigen level in patients treated with beads loaded with 2.5 mg of doxorubicine .
timeFrame: Three months after embolization
measure: Prostate-specific antigen level in patients treated with beads loaded with 5.0 mg of doxorubicine .
timeFrame: Day 14 before surgery
measure: Prostate-specific antigen level in patients treated with beads loaded with 5.0 mg of doxorubicine .
timeFrame: Day 30 (i.e. month after embolization)
measure: Prostate-specific antigen level in patients treated with beads loaded with 5.0 mg of doxorubicine .
timeFrame: Three months after embolization
measure: Prostate-specific antigen level in patients treated with beads loaded with 10.0 mg of doxorubicine .
timeFrame: Day 14
measure: Prostate-specific antigen level in patients treated with beads loaded with 10.0 mg of doxorubicine .
timeFrame: Day 30 (i.e. 1 month after embolization)
measure: Prostate-specific antigen level in patients treated with beads loaded with 10.0 mg of doxorubicine .
timeFrame: Three months after embolization
measure: Biological checkup for patients treated with beads loaded with 2.5 mg of doxorubicine
timeFrame: Three months after embolization
measure: Biological checkup for patients treated with beads loaded with 5.0 mg of doxorubicine
timeFrame: Three months after embolization
measure: Biological checkup for patients treated with beads loaded with 10.0 mg of doxorubicine
timeFrame: Three months after embolization
measure: Complete blood count for patients treated with beads loaded with 2.5 mg of doxorubicine
timeFrame: Three months after embolization
measure: Complete blood count for patients treated with beads loaded with 5.0 mg of doxorubicine
timeFrame: Three months after embolization
measure: Complete blood count for patients treated with beads loaded with 10.0 mg of doxorubicine
timeFrame: Three months after embolization
measure: Liver test for patients treated with beads loaded with 2.5 mg of doxorubicine
timeFrame: Three months after embolization
measure: Liver test for patients treated with beads loaded with 5.0 mg of doxorubicine
timeFrame: Three months after embolization
measure: Liver test for patients treated with beads loaded with 10.0 mg of doxorubicine
timeFrame: Three months after embolization
measure: Cardiac ultrasound and electrocardiogram for patients treated with beads loaded with 2.5 mg of doxorubicine
timeFrame: Three months after embolization
measure: Cardiac ultrasound and electrocardiogram for patients treated with beads loaded with 5.0 mg of doxorubicine
timeFrame: Three months after embolization
measure: Cardiac ultrasound and electrocardiogram for patients treated with beads loaded with 10.0 mg of doxorubicine
timeFrame: Three months after embolization
measure: Systemic dosage of free doxorubicin in blood in patients treated with beads loaded with 2.5 mg of doxorubicine
timeFrame: Day 1
Other outcomes:
Locations:
city: Nîmes
country: France
facility: Nîmes University Hospital
state: Gard
Study officials:
affiliation: CHU de Nîmes, Place du Professeur Debré, 30029 Nîmes Cedex
name: Anissa MEGZARI
role: STUDY_DIRECTOR
References: