EXPLANT: Study of the Response to Irradiation on Prostatic Explants ex Vivo, as a Predictive Factor of the Clinical Response to Irradiation of Prostate Cancers

Sponsor

Institut Cancerologie de l'Ouest (Other)

Overall Status

Recruiting

CT.gov ID

NCT03961737

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

1.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Of the 50,000 prostate cancers that occur each year in France, more than half will benefit from curative radiotherapy, alone or in combination with hormone therapy from 6 months to 3 years depending on the stage of the disease. At present, there are few ways to predict the response to this irradiation.

Evaluating the early response of tumor tissue to irradiation could predict the final response to treatment. It is difficult to offer biopsies during treatment for reasons of patient comfort. This is why this study consists in analysing transcriptomic and protein responses (immunohistochemistry) to irradiation on ex vivo prostate explants. These explants will be irradiated after culture and the transcriptional and immunohistochemical changes analysed before and after irradiation to determine an early tumor tissue response profile to irradiation.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	Procedure: prostate biopsies	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

92 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Other

Official Title:

Study of the Response to Irradiation on Prostatic Explants ex Vivo, as a Predictive Factor of the Clinical Response to Irradiation of Prostate Cancers

Actual Study Start Date :

Apr 2, 2019

Anticipated Primary Completion Date :

Jun 1, 2023

Anticipated Study Completion Date :

Jun 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: prostatic explants A first series of biopsies will be performed during the procedure to place the gold grains prior to radiotherapy. Explants will be performed from these biopsies. Half of these explants will be irradiated with a research irradiator at a dose of 2 Gy then placed for 24 hours in an appropriate culture medium. The other half will be directly cultured for 24 hours. After 24 hours of incubation, half of the irradiated explants and half of the explants will be used to study the transcriptome. The tissues will be stored in RNAlater solution and then frozen at -80°C. The remaining half explants will be used for immunohistochemical analysis. Two years after the end of radiotherapy, a new series of biopsies will be performed for research, in order to verify histologically the effectiveness of radiotherapy.	Procedure: prostate biopsies Before radiotherapy treatment, prostate biopsies will be performed in each patient. From these biopsies, explants will be performed. Half of these explants will be irradiated ex vivo and the other half will not receive any prior treatment. Then the patient will receive radiotherapy. It will be reviewed 2 years after the end of radiotherapy. New prostate biopsies will be performed to evaluate the tumor response to radiotherapy and to characterize the immunohistochemical and transcriptomic profiles of non-responder patients.

Arm

Intervention/Treatment

Experimental: prostatic explants

A first series of biopsies will be performed during the procedure to place the gold grains prior to radiotherapy. Explants will be performed from these biopsies. Half of these explants will be irradiated with a research irradiator at a dose of 2 Gy then placed for 24 hours in an appropriate culture medium. The other half will be directly cultured for 24 hours. After 24 hours of incubation, half of the irradiated explants and half of the explants will be used to study the transcriptome. The tissues will be stored in RNAlater solution and then frozen at -80°C. The remaining half explants will be used for immunohistochemical analysis. Two years after the end of radiotherapy, a new series of biopsies will be performed for research, in order to verify histologically the effectiveness of radiotherapy.

Procedure: prostate biopsies

Before radiotherapy treatment, prostate biopsies will be performed in each patient. From these biopsies, explants will be performed. Half of these explants will be irradiated ex vivo and the other half will not receive any prior treatment. Then the patient will receive radiotherapy. It will be reviewed 2 years after the end of radiotherapy. New prostate biopsies will be performed to evaluate the tumor response to radiotherapy and to characterize the immunohistochemical and transcriptomic profiles of non-responder patients.

Outcome Measures

Primary Outcome Measures

biopsy tumor response [24 months after radiotherapy]
The centralized anatomopathological study of prostate biopsies will classify patients into good responders (absence of viable tumour cells) and poor responders (persistence of viable tumour cells).

Secondary Outcome Measures

Change in Biochemical response to radiotherapy. [every 6 months for a maximum total of 24 months]
Biological response to radiotherapy the biological response to radiotherapy is assessed by measuring serum PSA levels according to Phoenix criteria, nadir 2 ng/ml
prostatic Magnetic Resonance Imaging [24 months after radiotherapy]
Prostate MRI 2 years after the end of radiotherapy, used to identify the area affected by the tumor

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Inclusion Criteria:

≥ 18 years old
Patient with non-operated prostate adenocarcinoma for whom radiotherapy treatment is scheduled
Signed Informed Consent
No contraindications to biopsy performance:

No anticoagulant treatment in progress
Absence of infection during diagnostic biopsies
Absence of pain requiring level 2 analgesics during diagnostic biopsies
Absence of bleeding complications during diagnostic biopsies
Absence of anal stenosis

Normal coagulation examination :

Prothrombin Ratio between 80 and 100%.
Active Cephalin Time from 24 to 41 seconds, > 1.5 times that of the indicator
Platelets > 150,000 G/L
International Normalised Ratio(INR) = 1 after stopping the anticoagulant

No contraindication to MRI:

Ocular metallic foreign body
Pacemaker
Old mechanical heart valve
Ancient vascular clips on cranial aneurysms

Exclusion Criteria:

History of radical prostatectomy. A history of transurethral prostate resection is not a contraindication
History of prostate infection
Hemorrhagic complications in diagnostic biopsies
Pain requiring level 2 analgesics in diagnostic biopsies
Anticoagulant treatment in progress (aspirin will be stopped 1 week before biopsies are performed)
Abnormal coagulation assessment
Anal stenosis
Contraindications to radiotherapy: chronic inflammatory bowel disease, scleroderma
Protected or tutored patient
Patient whose follow-up at two years is not possible

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	ICO	Saint-Herblain		France	44805

Sponsors and Collaborators

Institut Cancerologie de l'Ouest

Investigators

Principal Investigator: Stéphane SUPIOT, MD, ICO

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Institut Cancerologie de l'Ouest

ClinicalTrials.gov Identifier:

NCT03961737

Other Study ID Numbers:

ICO-N-2016-05

First Posted:

May 23, 2019

Last Update Posted:

Apr 22, 2022

Last Verified:

Apr 1, 2022

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Institut Cancerologie de l'Ouest

Additional relevant MeSH terms:

Prostatic Neoplasms

Study Results

No Results Posted as of Apr 22, 2022