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Active, not recruitingNCT03438552STEREO-RE-PROUpdated Dec 20, 2024

Efficacy of Repeat Stereotactic Radiation in Patients With Intraprostatic Tumor Recurrence

An interventional study of Stereotactic Body Radiotherapy in Local Recurrence of Malignant Tumor of Prostate, sponsored by UNICANCER. Active, not recruiting at 12 sites in France. Open to male participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-12-20.

Sponsored by UNICANCER · Not applicable, Interventional, and Treatment

Phase
Not applicable
Study type
Interventional
Enrollment
57
Allocation
Randomized
Ages
18 Years and older
Sex
Male
01

Study summary

Stereo-Re-Pro aims to provide further evidence of Stereotactic Body Radiotherapy (SBRT) as a supplementary non-invasive curative treatment for local recurrence following radiotherapy.

The objective of the first part of the trial (Phase I) is to select the recommended dose for salvage SBRT (either 5 x 6 Gy, 6 x 6 Gy, or 5 x 5 Gy) based on dose-limiting toxicity observed during the 18 weeks following the initiation of salvage-SBRT. Particular attention will be paid to the quality of life and tolerance of the treatment.

The objective of the second part of the trial (phase II) is to estimate the efficacy of the salvage-SBRT in terms of biochemical relapse-free survival rate.

Read the detailed description

To date, no standard local treatment exists for patients with an intraprostatic recurrence after radiotherapy. A number of treatments options exist including: radical prostatectomy, brachytherapy, High-intensity focused ultrasound (HIFU), cryotherapy, and stereotactic radiotherapy. These treatments are associated with a variety of genitourinary and gastrointestinal toxicities and complications. In recent years, stereotactic radiotherapy has been used to treat localized prostate cancer in the primary setting but also as a salvage treatment after failure of radiotherapy. The initial results of these studies are promising, with respect to survival and tolerance, but further studies are required to confirm these initial results.

The objective of STEREO-RE-PRO is to prospectively evaluate salvage SBRT for intraprostatic recurrent prostate cancer after primary external radiotherapy. This study will select patients for whom there is no standard local treatment.

After inclusion and non-inclusion criteria have been verified and the patient has consented, the site will register the screening and organize the baseline visit with the placement of fiducial markers within two months before the planned start of SBRT.

Once the fiducial placement has been performed and all eligibility criteria fully reviewed, the site will register the patient's participation so that the bio-statistician allocates the dose of SBRT. The dose will be allocated upon a model-based estimates provided by the statistical team and confirmed by the trial steering committee. Five or six fractions, at a level of 5 or 6 Gy per session (either 5 x 6 Gy, 6 x 6 Gy, or 5 x 5 Gy), will be delivered over a maximum of 12 days to provide a total dose of 25 to 36 Gy. During the treatment phase of the study, no study specific visits are scheduled and the patients will be followed as per standard of care.

A follow-up visit is planned at 6, 10, 18 weeks from the start of SBRT for safety evaluation. Subsequent follow-up visits are planned at 6, 9, 12, 18, 24, 30, and 36 months after the start of radiotherapy. Thereafter, yearly follow-up visits at 48, 60, and 72 months after starting SBRT will be planned after the initial 3-year follow-up period. M72 visit corresponds to the end of study visit.

02

Conditions studied

  • Local Recurrence of Malignant Tumor of Prostate
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
Male
Accepts healthy volunteers
No

Inclusion criteria

  • Biochemical recurrence occurring at least 2 years after external radiotherapy for prostatic adenocarcinoma by the Phoenix definition (PSA nadir + 2 ng/mL)
  • T1-T2c and PSA ≤20 ng/mL and Gleason score ≤7 at initial diagnosis of prostate cancer before the initial/first treatment.
  • Recurrence of prostatic adenocarcinoma proven by histology following radiotherapy by transrectal or transperineal sextant biopsies of the two lobes of the prostate, with a minimum of 12 biopsies, irrespective of Gleason score. Biopsies of the seminal vesicles are optional.
  • Clinical stage T1-T2 on relapse; unilateral extracapsular extension (T3a) on MRI permitted except posteriorly relative to the rectum
  • Estimated clinical target volume (CTV) / prostate volume \< 0.5 based on imaging and biopsies
  • Pelvic and prostatic assessment by multiparametric MRI- Absence of pelvic or metastatic recurrence proven by choline PET scan
  • Performance status World Health Organization (WHO) 0-1
  • PSA level ≤10 ng/mL at baseline (before salvage-SBRT)
  • PSA doubling time >10 months
  • International Prostate Cancer Score (IPSS) ≤12
  • Uroflowmetry with a maximum flow rate >10 mL/s, a postvoid residual urine volume \<150 mL, and a urine volume >150 mL.
  • No other anti-cancer treatment since the external radiotherapy administered as first-line treatment
  • No other anti-cancer treatment planned for the current recurrence
  • No contraindication to fiducial marker implants; haemostatic disorders must be corrected before implantation
  • Age >18 years
  • Life-expectancy greater than or equal to 5 years (Lee scale)
  • Patient registered with a health insurance system
  • Patient who has signed the informed consent form
  • Patients willing and able to comply with the scheduled visits, treatment plan, laboratory tests, and other study procedures indicated in the protocol.

Exclusion criteria

Exclusion Criteria:

  • Lymph node or metastatic spread
  • Late post-radiotherapy urinary or gastrointestinal toxicity of grade ≥2 (following primary radiotherapy)
  • Other cancers in the last 5 years except for non-melanoma-type skin cancer
  • History of inflammatory bowel disease
  • Anticoagulant treatment
  • Contraindications to undergoing MRI
  • Prostate volume >80 cc
  • Transurethral resection of the prostate (TURP) in the 6 months before registrations
  • Presence of rectal telangiectasia grade 3 classified by the Vienna Rectoscopy Score (obligatory rectoscopy)
  • Previous rectal surgery
  • Patients unable to undergo medical follow-up in the study for geographical, social or psychological
  • Person deprived of their liberty or under protective custody or guardianship
  • Patients enrolled in another therapeutic study

All patients during the SBRT planning with a ratio of clinical target volume (CTV) / prostate volume >0.5 will be withdrawn from the study. These patients will be considered as not evaluable and will not be treated within the context of the study.

04

Study design

Phase
Not applicable
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Sequential assignment
Masking
None (open label)
Enrollment
57 participants (actual)

Study arms

  • Experimental
    SBRT at a total dose of 30 Gy

    Placement of fiducials marker seeds in the prostate followed by the administration of stereotactic body radiotherapy at 30 Gy (5 sessions at a level of 6 Gy each- 1 session per day) 30 Gy is the first dose-level. During the treatment phase of the study, no study specific visits are scheduled and the patients will be followed as per standard of care.

    Radiation: Stereotactic Body Radiotherapy

  • Experimental
    SBRT at a total dose of 25 Gy

    Placement of fiducials marker seeds in the prostate followed by the administration of stereotactic body radiotherapy at 25 Gy (5 sessions at a level of 5 Gy each- 1 session per day) During the treatment phase of the study, no study specific visits are scheduled and the patients will be followed as per standard of care.

    Radiation: Stereotactic Body Radiotherapy

  • Experimental
    SBRT at a total dose of 36 Gy

    Placement of fiducials marker seeds in the prostate followed by the administration of stereotactic body radiotherapy at 36 Gy (6 sessions at a level of 6 Gy each- 1 session per day) During the treatment phase of the study, no study specific visits are scheduled and the patients will be followed as per standard of care.

    Radiation: Stereotactic Body Radiotherapy

Interventions

  • RadiationStereotactic Body Radiotherapy

    This radiotherapy may be administered with the CyberKnife® or a linear accelerator allowing stereotactic radiotherapy.

05

What researchers measure

Primary outcomes

  1. Selection of the recommended dose for salvage-SBRT (either 5 x 6 Gy, 6 x 6 Gy, or 5 x 5 Gy) based on dose-limiting toxicity observed during the 18 weeks following the initiation of salvage-SBRT.

    The dose-escalation part of the study will terminate once 10 patients have been treated and evaluated at a dose currently identified as the recommended dose.

    Time frame: 18 weeks

  2. Estimate the efficacy of the salvage-SBRT in terms of biochemical relapse-free survival rate

    Time frame: 6 years

Secondary outcomes

  1. Evaluation of acute and late genitourinary toxicities of the salvage-SBRT

    Acute and late genitourinary toxicities over the first 3 years according to the NCI-CTCAE V4.03 classification (June 14th, 2010)

    Time frame: 3 years

  2. Estimate the efficacy of the salvage-SBRT in terms of clinical progression-free survival and overall survival

    Clinical progression-free survival is defined as the time interval between the date of registration and the date of clinical progression (local progression assessed by the physical examination, or appearance of metastatic lesions) or death irrespective of the cause.

    Time frame: 6 years

  3. Evaluation of Quality of life after salvage-SBRT

    Quality of life will be evaluated based on the EORTC QLQ-C30. The Time Until Definitive Deterioration (TUDD) will be computed from registration until the first observation of a definitive deterioration of the quality of life, defined as a score decreased by 10 points (in the case of global health scale and functional scales) or increased by 10 points (in the case of symptom scales) compared to the score at baseline, without later improvement superior to 10 points compared to baseline score.

    Time frame: 6 years

  4. Evaluation of Quality of life after salvage-SBRT

    Quality of life will be evaluated based on the EORTC QLQ-PR25. The Time Until Definitive Deterioration (TUDD) will be computed from registration until the first observation of a definitive deterioration of the quality of life, defined as a score decreased by 10 points (in the case of global health scale and functional scales) or increased by 10 points (in the case of symptom scales) compared to the score at baseline, without later improvement superior to 10 points compared to baseline score.

    Time frame: 6 years

06

Study locations

12 sites
  • Centre François Baclesse
    Caen, 14000, France
  • Centre Jean Perrin
    Clermont-Ferrand, 63011, France
  • Centre George François Leclerc
    Dijon, 21079, France
  • Centre Oscar Lambret
    Lille, 59020, France
  • Centre Léon Bérard
    Lyon, 69008, France
  • Institut régional du Cancer de Montpellier
    Montpellier, 34298 CEDEX 05, France
  • Groupe Hospitalier Pitié-Salpétrière
    Paris, 75013, France
  • DE CREVOISIER Renaud
    Rennes, 35042, France
  • ICO -Site René Gauducheau
    Saint-Herblain, 44805, France
  • Institut de Cancérologie Lucien Neuwirth
    Saint-Priest-en-Jarez, 42270, France
  • CHRU Henry S.Kaplan
    Tours, 37044, France
  • Institut de Cancérologie de Lorraine
    Vandoeuvre-les-nancy, 54519, France
07

References and documents

Publications

  • Pasquier D, Le Deley MC, Tresch E, Cormier L, Duterque M, Nenan S, Lartigau E. GETUG-AFU 31: a phase I/II multicentre study evaluating the safety and efficacy of salvage stereotactic radiation in patients with intraprostatic tumour recurrence after external radiation therapy-study protocol. BMJ Open. 2019 Aug 2;9(8):e026666. doi: 10.1136/bmjopen-2018-026666. PubMed 31377694 ↗

Individual participant data

Plan to share: Undecided

08

Registry details

Key details

Study ID
NCT03438552
Lead sponsor
UNICANCER
Responsible party
Sponsor
First posted
Feb 19, 2018
Start date
Oct 18, 2018
Primary completion
Oct 15, 2027 (estimated)
Completion
Nov 2030 (estimated)
Last update
Dec 20, 2024

Study contacts

David Pasquier
principal investigator · Centre Oscar Lambret, LILLE

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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