Salvage Brachytherapy and Interstitial Hyperthermia for Locally Recurrent Prostate Carcinoma Following Radiation Therapy

Study Overview
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Brief Summary
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Salvage brachytherapy in combination with interstitial hyperthermia for locally recurrent prostate carcinoma following external beam radiation therapy.

Detailed Description
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Salvage brachytherapy in combination with interstitial hyperthermia for locally recurrent prostate carcinoma following external beam radiation therapy: Salvage brachytherapy: HDRBT: 3 x 10 Gy specified on prostate capsule/tumor margin (d1, 22, 43) or PDRBT: 2 x 30 Gy specified on prostate capsule/tumor margin (d1-3, 29-31) Hyperthermia: prostate heated to 40 - 47˚C for 30-60 minutes (60 minutes recommended) prior to brachytherapy dose delivery. Maximum temperature in surrounding critical normal organs should not exceed 43˚C

Official Title
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A Prospective Phase II Study of Salvage Brachytherapy in Combination With Interstitial Hyperthermia for Locally Recurrent Prostate Carcinoma Following External Beam Radiation Therapy

Conditions
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Prostate Cancer

Intervention / Treatment
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* Radiation: Brachytherapy
* Other: Hyperthermia


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically-confirmed locally recurrent prostate cancer - biopsy performed < 6 months before registration; Histology: Adenocarcinoma, every Gleason score (2-10) Initial treatment (EBRT) completed > 24 months prior to biopsy; Androgen deprivation therapy for prostate cancer should be discontinued at least 3 months prior to patient registration Staging performed within 12 weeks prior to registration: Local stage evaluated by DRE, TRUS or - if necessary - mpMRI (T1b, T1c, T2a, T2b, T2c, T3a, T3b); Negative lymph nodes by imaging studies (at least one of these: choline PET scan, pelvic ± abdominal CT or MRI) or by lymphadenectomy (cN0 or pN0); Negative bone scan (M0); PSA-DT > 6 months (PSA measurements taken of the 12 months prior to registration) Zubrod Performance Scale 0-2 (Appendix V) International Prostate Symptoms Score (IPSS) < 20 (Appendix VI), the IPSS score can be evaluated in patient on alpha-blockers; Baseline gastrointestinal (GI) or genitourinary (GU) toxicity grade 0-1 as defined in Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. In TRUS volume study performed 0-4 weeks before registration patient meets eligibility criteria for prostate brachytherapy as follows: Prostate/tumor volume <60ml The distance rear prostate edge - rectal mucosa >5mm Interference of pubic arch ruled out If local stage T3b: it must be possible to cover by the brachytherapy dose cancer infiltration Prostate lenght (from apex plane to base plane) ≤ 45mm (technical criterion for 915 MHz frequency antennas) The patient is suitable for spinal or general anesthesia Age > 18 y. Life expectancy > 5 years absence of any 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 The patient must sign a study-specific informed consent form before study registration Exclusion Criteria: Severe, active comorbidities: Decompensated congestive heart disease Chronic obstructive pulmonary disease exacerbation, respiratory failure Hepatic insufficiency resulting in coagulation defects or clinical jaundice Other active malignancy or treatment of invasive or hematological malignancy Evidence of extraprostatic disease at local recurrence: Local stage T4 Histologic or radiologic evidence of lymph node metastases (N1 or pN1) Presence of distant metastases (M1) Any of the following prior therapies: TURP within 6 months prior to registration Prostatic salvage cryosurgery performed at least 6 months before registration HIFU performed at least 6 months before registration Androgen deprivation therapy within 3 months prior to registration Baseline gastrointestinal (GI) or genitourinary (GU) toxicity grade ≥ 2 as defined in Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Arm<br>The physician can choose either HDR or PDR brachytherapy. If HDR BT is chosen: d1: hyperthermia (IHT) 60 minutes + 10Gy HDR brachytherapy (HDRBT) d22: IHT 60 minutes + 10 Gy HDRBT d43: IHT 60 minutes + 10 Gy HDRBT If PDR BT is chosen: d1-3: IHT 60 minutes + 30Gy PDRBT d29-31: IHT 60 minutes + 30Gy PDRBT | Radiation: Brachytherapy<br>* HDR/PDR brachytherapy<br>Other: Hyperthermia<br>* Interstitial hyperthermia<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of late GI/GU grade 3 and more toxicities |  | up to 60 Months in Follow up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of acute GI/GU treatment-related adverse events |  | up to 24 months after start of recruitment | 
| Time to biochemical failure | defined rise of PSA | up to 60 Months in Follow up | 
| Overall survival |  | up to 60 Months in Follow up | 
| Disease-free survival |  | up to 60 Months in Follow up | 
| Disease-specific survival |  | up to 60 Months in Follow up | 
| Clinical patterns of tumor recurrence |  | up to 60 Months in Follow up |