Safety, Tolerability, Distribution & Dose Effect of Neoadjuvant Transarterial Chemoembolization With Doxorubicin in Prostate Cancer Patients Before Radical Prostatectomy

NCT04423913 | Terminated Phase 2

• 3 other identifiers: NIMAO/2018-01/JF-012019-001920-362019-A02946-51
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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).

Conditions

Prostate Cancer

Keywords

doxorubicin; beads; embolization; chemoembolization; prostate cancer

Outcome Measures

Primary Outcomes (24)

• Evaluation of safety of prostate embolization using unloaded beads.

  The number of serious undesirable events will be noted during the embolization. The undesirable event noted will be: non-targeted necrosis, intense vesicle or rectal pain, rectal bleeding, abundant hematuria and fever.

  Day 0 (i.e. on the day of the intervention)

• Evaluation of safety of prostate embolization using unloaded beads.

  The number of serious undesirable events will be noted the day after embolization. The undesirable events noted will be: non-targeted necrosis, intense vesicle or rectal pain, rectal bleeding, abundant hematuria and fever.

  Day 1 (i.e. one day after the intervention)

• Evaluation of safety of prostate embolization using unloaded beads.

  The number of serious undesirable events will be noted by telephone. The undesirable events noted will be: non-targeted necrosis, intense vesicle or rectal pain, rectal bleeding, abundant hematuria and fever.

  Day 5 (i.e. 5 days after the intervention)

• Evaluation of safety of prostate embolization using unloaded beads.

  This will be evaluated by magnetic resonance imaging (vesicular or rectal necrosis, fistula or abcess) and at the time of surgery.The undesirable events noted will be: non-targeted necrosis, intense vesicle or rectal pain, rectal bleeding, abundant hematuria and fever.

  Day 14 (i.e. 2 weeks after the intervention)

• Evaluation of safety of prostate embolization using unloaded beads.

  Evaluation of post-operative complications. The undesirable events noted will be: non-targeted necrosis, intense vesicle or rectal pain, rectal bleeding, abundant hematuria and fever.

  Day 30 (i.e. 1 month after the intervention)

• Evaluation of safety of prostate embolization using unloaded beads.

  Evaluation of post-operative complications. The undesirable events noted will be: non-targeted necrosis, intense vesicle or rectal pain, rectal bleeding, abundant hematuria and fever.

  Three months after the intervention

• Evaluation of safety of prostate embolization using beads loaded with 2.5 mg of doxorubicin

  The number of serious undesirable events will be noted during the embolization. The undesirable events noted will be: non-targeted necrosis, intense vesicle or rectal pain, rectal bleeding, abundant hematuria and fever.

  Day 0 (i.e. on the day of the intervention)

• Evaluation of safety of prostate embolization using beads loaded with 2.5 mg of doxorubicin

  The number of serious undesirable events will be noted after the embolization. The undesirable events noted will be: non-targeted necrosis, intense vesicle or rectal pain, rectal bleeding, abundant hematuria and fever.

  Day 1 (i.e. one day after the intervention)

• Evaluation of safety of prostate embolization using beads loaded with 2.5 mg of doxorubicin

  The number of serious undesirable events will be noted by telephone. The undesirable events noted will be: non-targeted necrosis, intense vesicle or rectal pain, rectal bleeding, abundant hematuria and fever.

  Day 5 (i.e. 5 days after the intervention)

• Evaluation of safety of prostate embolization using beads loaded with 2.5 mg of doxorubicin

  This will be evaluated by magnetic resonance imaging (vesicular or rectal necrosis, fistula or abcess) and at the time of surgery.The undesirable events noted will be: non-targeted necrosis, intense vesicle or rectal pain, rectal bleeding, abundant hematuria and fever.

  Day 14 (i.e. 2 weeks after the intervention)

• Evaluation of safety of prostate embolization using beads loaded with 2.5 mg of doxorubicin

  Postoperative complications. The undesirable events noted will be: non-targeted necrosis, intense vesicle or rectal pain, rectal bleeding, abundant hematuria and fever.

  Day 30 (i.e. 1 month after the intervention)

• Evaluation of safety of prostate embolization using beads loaded with 2.5 mg of doxorubicin

  Postoperative complications. The undesirable events noted will be: non-targeted necrosis, intense vesicle or rectal pain, rectal bleeding, abundant hematuria and fever.

  Three months after the intervention

• Evaluation of safety of prostate embolization using beads loaded with 5.0 mg of doxorubicin

  The number of serious undesirable events will be noted during the embolization. The undesirable events noted will be: non-targeted necrosis, intense vesicle or rectal pain, rectal bleeding, abundant hematuria and fever.

  Day 0 (i.e. on the day of the intervention)

• Evaluation of safety of prostate embolization using beads loaded with 5.0 mg of doxorubicin

  The number of serious undesirable events will be noted after the embolization. The side effects noted will be: non-targeted necrosis, intense vesicle or rectal pain, rectal bleeding, abundant hematuria and fever.

  Day 1 (i.e. one day after the intervention)

• Evaluation of safety of prostate embolization using beads loaded with 5.0 mg of doxorubicin

  The number of serious undesirable events will be noted by telephone. The undesirable events noted will be: intense vesicle or rectal pain, rectal bleeding, abundant hematuria and fever.

  Day 5 (i.e. 5 days after the intervention)

• Evaluation of safety of prostate embolization using beads loaded with 5.0 mg of doxorubicin

  This will be evaluated by magnetic resonance imaging (vesicular or rectal necrosis, fistula, abcess) and at the time of surgery.The undesirable events noted will be: non-targeted necrosis, intense vesicle or rectal pain, rectal bleeding, abundant hematuria and fever.

  Day 14 (i.e. 2 weeks after the intervention)

• Evaluation of safety of prostate embolization using beads loaded with 5.0 mg of doxorubicin

  Postoperative complications. The undesirable events noted will be: non-targeted necrosis, intense vesicle or rectal pain, rectal bleeding, abundant hematuria and fever.

  Day 30 (i.e. 1 month after the intervention)

• Evaluation of safety of prostate embolization using beads loaded with 5.0 mg of doxorubicin

  Postoperative complications. The undesirable events noted will be: non-targeted necrosis, intense vesicle or rectal pain, rectal bleeding, abundant hematuria and fever.

  3 months after the intervention

• Evaluation of safety of prostate embolization using beads loaded with 10.0 mg of doxorubicin

  The number of serious undesirable events will be noted during the embolization. The undesirable events noted will be: non-targeted necrosis, intense vesicle or rectal pain, rectal bleeding, abundant hematuria and fever.

  Day 0 (i.e. on the day of the intervention)

• Evaluation of safety of prostate embolization using beads loaded with 10.0 mg of doxorubicin

  The number of serious undesirable events will be noted after the clinical embolization. The undesirable events noted will be: non-targeted necrosis, intense vesicle or rectal pain, rectal bleeding, abundant hematuria and fever.

  Day 1 (i.e. one day after the intervention)

• Evaluation of safety of prostate embolization using beads loaded with 10.0 mg of doxorubicin

  The number of serious undesirable events will be noted by telephone. The undesirable events noted will be: intense vesicle or rectal pain, rectal bleeding, abundant hematuria and fever.

  Day 5 (i.e. 5 days after the intervention)

• Evaluation of safety of prostate embolization using beads loaded with 10.0 mg of doxorubicin

  This will be evaluated by magnetic resonance imaging (vesicular or rectal necrosis, fistula, abcess) and at the time of surgery.The undesirable events noted will be: non-targeted necrosis, intense vesicle or rectal pain, rectal bleeding, abundant hematuria and fever.

  Day 14 (i.e. 2 weeks after the intervention)

• Evaluation of safety of prostate embolization using beads loaded with 10.0 mg of doxorubicin

  Postoperative complications. The undesirable events noted will be: intense vesicle or rectal pain, rectal bleeding, abundant hematuria and fever.

  Day 30 (i.e. 1 month after the intervention)

• Evaluation of safety of prostate embolization using beads loaded with 10.0 mg of doxorubicin

  Postoperative complications. The undesirable events noted will be: intense vesicle or rectal pain, rectal bleeding, abundant hematuria and fever.

  Three months after the intervention

Secondary Outcomes (81)

• Tolerance of prostate embolization using unloaded beads.

  Day 14

• Tolerance of prostate embolization using beads loaded with 2.5 mg of doxorubicin.

  Day 14

• Tolerance of prostate embolization using beads loaded with 5.0 mg of doxorubicin.

  Day 14

• Tolerance of prostate embolization using beads loaded with 10.0 mg of doxorubicin.

  Day 14

• Tolerance of prostate embolization using unloaded beads: Clavien-Dindo score

  Day 14

Study Arms (4)

Patients undergoing transarterial embolization of the prostate

EXPERIMENTAL

Three patients will undergo transarterial embolization of the prostate using unloaded beads.

Other: Administration of embolization beads

Transarterial prostatic chemoembolization, 2.5 mg doxorubicin

EXPERIMENTAL

Three patients will undergo transarterial chemoembolization of the prostate using beads loaded with 2.5 mg of doxorubicin.

Other: Administration of embolization beads

Transarterial prostatic chemoembolization, 5.0 mg doxorubicin

EXPERIMENTAL

Three patients will undergo transarterial chemoembolization of the prostate using beads loaded with 5.0 mg of doxorubicin.

Other: Administration of embolization beads

Transarterial prostatic chemoembolization, 10.0 mg doxorubicin

EXPERIMENTAL

Three patients will undergo transarterial chemoembolization of the prostate using beads loaded with 10.0 mg of doxorubicin.

Other: Administration of embolization beads

Interventions

Administration of embolization beads OTHER

Patients will receive embolization beads, loaded with doxorubicin or not.

Patients undergoing transarterial embolization of the prostate; Transarterial prostatic chemoembolization, 10.0 mg doxorubicin; Transarterial prostatic chemoembolization, 2.5 mg doxorubicin; Transarterial prostatic chemoembolization, 5.0 mg doxorubicin

Eligibility Criteria

• Age: 18 Years - 80 Years
• Gender Eligibility Details: As the study relates to embolization of prostate cancer, only male patients are concerned.
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• Patients who are taking part in another 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 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.

Sponsors & Collaborators

• Centre Hospitalier Universitaire de Nīmes: lead

Study Sites (1)

Nîmes University Hospital

Nîmes, Gard, 30029, France

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Study Officials

• Anissa MEGZARI

  CHU de Nîmes, Place du Professeur Debré, 30029 Nîmes Cedex

  STUDY DIRECTOR

Study Design

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

Model Details: 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.

Study Record Dates

• First Submitted: June 5, 2020
• First Posted: June 9, 2020
• Study Start: May 4, 2022
• Primary Completion: June 1, 2022
• Study Completion: October 31, 2022
• Last Updated: March 27, 2023

Record last verified: 2023-03

Locations

FR (1)