Charité HT-Prostate

Phase II Studie Zur Hyperthermen Salvage-Radiotherapie Bei Prostatakarzinompatienten Mit Biochemischem Rezidiv Nach Prostatektomie

The combination of regional hyperthermia and salvage radiotherapy is being tested in patients with biochemically recurrent prostate cancer after radical prostatectomy.

Study Overview

• Status: Recruiting
• Conditions: Recurrence; Prostate Cancer
• Intervention / Treatment: Device: Regional Hyperthermia

Detailed Description

Current studies on salvage radiotherapy (sRT) for biochemically recurrent prostate cancer after radical prostatectomy investigate timing, dose-escalation and androgen deprivation therapy (ADT) for recurrent prostate cancer. These approaches could either be limited by radiation-related susceptibility of the anastomosis or by suspected side-effects of ADT. A phase II protocol was developed to investigate the benefit and tolerability of regional hyperthermia with moderately dose-escalated sRT. The study hypothesis is that hyperthermic sRT is a safe and feasible salvage treatment modality. The primary endpoint is safety measured by frequency of grade 3+ genitourinary (GU) and gastrointestinal (GI) adverse events (AE) according to Common Toxicity Criteria (CTC) version 4. Feasibility is defined by number of hyperthermia treatments (n ≥ 7) and feasibility of sRT according to protocol. Target volume delineation is performed according to the EORTC guidelines. sRT is administered with single doses of 2 Gy 5×/week to a total dose of 70 Gy to the prostate bed, or alternatively the total dose only to the area of highest risk and a lower dose to the remaining prostate bed using a simultaneous boost (SIB) technique. Regional hyperthermia is given 2×/week to a total of 10 treatments. German centres participate in the phase II trial using intensity modulated RT (IMRT), volumetric modulated arc technique (VMAT) or tomotherapy. The initiating centres were participants of the SAKK 09/10 study, where the same patient criteria and target volume definition (mandatory successful performed dummy run) were applied insuring a high standardisation of the study procedures.

The introduced phase II study implements modern sRT and regional hyperthermia. If the phase II study is found to be safe and feasible, a multicenter phase III study might be performed to test whether the addition of regional hyperthermia to dose-intensified sRT improves biochemical control.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Pirus Ghadjar, Prof. Dr.; Email: pirus.ghadjar@charite.de

Study Locations

• Germany
  • Berlin, Germany, 13353
    • Recruiting
    • Charité Universitätsmedizin Berlin
    • Contact: Pirus Ghadjar, Prof. Dr.; Email: pirus.ghadjar@charite.de
    • Contact: Marcus Beck, MD; Email: marcus.beck@charite.de
    • Principal Investigator: Marcus Beck, MD
    • Sub-Investigator: Sebastian Zschaeck, MD
    • Sub-Investigator: Peter Wust, Prof. Dr.
  • Baden Württemberg
    • Tübingen, Baden Württemberg, Germany, 72016
      • Recruiting
      • Universitatsklinikum Tubingen
      • Principal Investigator: Arndt-Christian Müller, MD
      • Contact: Arndt-Christian Müller, MD; Email: Arndt-Christian.Mueller@med.uni-tuebingen.de
  • Bayern
    • Erlangen, Bayern, Germany, 91012
      • Recruiting
      • Universitatsklinikum Erlangen
      • Contact: Oliver Ott, Prof. Dr.; Email: oliver.ott@uk-erlangen.de
      • Principal Investigator: Oliver Ott, Prof. Dr.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. Lymph node negative adenocarcinoma of the prostate treated with radical prostatectomy at least 12 weeks before randomization. Tumour stage pT2a-3b, R0-1, pN0 or cN0 according to the UICC TNM 2009; Gleason score available.
2. PSA progression after prostatectomy defined as two consecutive rises with the final PSA > 0.1 ng/ml or three consecutive rises. The first value must be measured at least 4 weeks after radical prostatectomy.
3. PSA at randomization ≤ 2 ng/ml.
4. No evidence of macroscopic local recurrence or metastatic disease on pre-sRT-MRI (magnetic resonance imaging; with i.v. contrast) or pre-sRT-CT (multislice computed tomography with i.v. and oral contrast) of the abdomen and pelvis assessed within 16 weeks prior to randomization.
5. WHO performance status 0-1 at randomization.
6. Age at randomization between 18 and 80 years.
7. Informed consent.

Exclusion Criteria:

1. Persistent PSA value 4-20 weeks after radical prostatectomy > 0.4 ng/ml.
2. Palpable mass in the prostatic fossa, unless histology proves no evidence of recurrence.
3. Pelvic lymph node enlargement >1 cm in short axis diameter of the abdomen and pelvis (cN1), unless the enlarged lymph node is sampled and negative.
4. Presence or history of bone metastases. Bone scan is mandatory in cases of clinical suspicion (e.g., bone pain).
5. Other malignancies within five years before planned sRT; non-melanoma skin cancers are allowed.
6. ADT or bilateral orchiectomy.
7. Previous pelvic radiotherapy.
8. Hip prosthesis.
9. Metal clusters/markers and patients with a pacemaker.

10. Severe or active co-morbidities impairing the feasibility of hyperthermia or dose intensified sRT including (but not exclusively limited to):

    • chronic inflammatory bowel disease
    • acute bacterial or fungal infection requiring intravenous antibiotics at the time of randomization
    • unstable angina pectoris and/or congestive heart failure requiring hospitalization within the last 6 months
    • transmural myocardial infarction within the last 6 months
    • chronic obstructive pulmonary disease exacerbation or other respiratory disorders requiring hospitalization or precluding planned treatment within the study at the time of randomization
    • psychiatric disorder precluding understanding of information on trial-related topics, giving informed consent or filling out QoL questionnaires
11. Concurrent treatment with other experimental drugs or other anti-cancer therapy; treatment in a clinical trial within 30 days prior to trial entry.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Combined regional hyperthermia and salvage radiotherapy	Device: Regional Hyperthermia; Regional hyperthermia 1-2×/week to a total number of 7-10 treatments combined with salvage radiotherapy to a total dose of 70 Gy over 7 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute grade 3+ adverse events	Measured according to CTCAE version 4.	up to three months after end of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Late adverse events	According to CTCAE version 4.	up to 36 months after end of treatment
Quality of life (QoL) assessment	Using EORTC questionnaires	up to 36 months after end of treatment
Biochemical progression-free survival	PSA-rise > 0.4 ng/ml or increasing PSA-level where the initial PSA-level is above 0.4 ng/ml.	up to 36 months after end of treatment
Clinical progression-free survival	Occurrence of a local recurrence, regional recurrence or distant metastasis. Clinical progression-free survival is defined as the time between trial inclusion and occurrence of clinical progression, start of a new androgen deprivation therapy (see below) or death. Patients without event will be censored at the time of last follow-up.	up to 36 months after end of treatment
Time without androgen deprivation therapy (ADT), i.e., time until initiation of ADT	The time from trial inclusion until start of a new androgen deprivation therapy. Patients without new ADT will be censored at the time of last follow-up.	up to 36 months after end of treatment

Collaborators and Investigators

• Sponsor: Charite University, Berlin, Germany

Publications and helpful links

General Publications

• Muller AC, Zips D, Heinrich V, Lamprecht U, Voigt O, Burock S, Budach V, Wust P, Ghadjar P. Regional hyperthermia and moderately dose-escalated salvage radiotherapy for recurrent prostate cancer. Protocol of a phase II trial. Radiat Oncol. 2015 Jul 8;10:138. doi: 10.1186/s13014-015-0442-4.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2016
• Primary Completion (Anticipated): January 1, 2021
• Study Completion (Anticipated): January 1, 2024

Study Registration Dates

• First Submitted: November 6, 2019
• First Submitted That Met QC Criteria: November 7, 2019
• First Posted (Actual): November 12, 2019

Study Record Updates

• Last Update Posted (Actual): November 12, 2019
• Last Update Submitted That Met QC Criteria: November 7, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Recurrence
• Other Study ID Numbers: EA2/110/15

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No