Charité HT-Prostate

• ClinicalTrials.gov Identifier: NCT04159051
• Recruitment Status: Recruiting
• First Posted: November 12, 2019
• Last Update Posted: November 12, 2019
• Sponsor: Charite University, Berlin, Germany
• Information provided by (Responsible Party): Pirus Ghadjar, Charite University, Berlin, Germany

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Prostate Cancer; Recurrence	Device: Regional Hyperthermia	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 100 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Studie Zur Hyperthermen Salvage-Radiotherapie Bei Prostatakarzinompatienten Mit Biochemischem Rezidiv Nach Prostatektomie
• Actual Study Start Date: October 2016
• Estimated Primary Completion Date: January 2021
• Estimated Study Completion Date: January 2024

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Acute grade 3+ adverse events [ Time Frame: up to three months after end of treatment ]
   Measured according to CTCAE version 4.

Secondary Outcome Measures :

1. Late adverse events [ Time Frame: up to 36 months after end of treatment ]
   According to CTCAE version 4.
2. Quality of life (QoL) assessment [ Time Frame: up to 36 months after end of treatment ]
   Using EORTC questionnaires
3. Biochemical progression-free survival [ Time Frame: up to 36 months after end of treatment ]
   PSA-rise > 0.4 ng/ml or increasing PSA-level where the initial PSA-level is above 0.4 ng/ml.
4. Clinical progression-free survival [ Time Frame: up to 36 months after end of treatment ]
   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.
5. Time without androgen deprivation therapy (ADT), i.e., time until initiation of ADT [ Time Frame: up to 36 months after end of treatment ]
   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.

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Contacts

Contact: Pirus Ghadjar, Prof. Dr.; pirus.ghadjar@charite.de

Locations

Germany

Universitätsklinikum Tübingen; Recruiting

Tübingen, Baden Württemberg, Germany, 72016

Contact: Arndt-Christian Müller, MD Arndt-Christian.Mueller@med.uni-tuebingen.de

Principal Investigator: Arndt-Christian Müller, MD

Universitätsklinikum Erlangen; Recruiting

Erlangen, Bayern, Germany, 91012

Contact: Oliver Ott, Prof. Dr. oliver.ott@uk-erlangen.de

Principal Investigator: Oliver Ott, Prof. Dr.

Charité Universitätsmedizin Berlin; Recruiting

Berlin, Germany, 13353

Contact: Pirus Ghadjar, Prof. Dr. pirus.ghadjar@charite.de

Contact: Marcus Beck, MD marcus.beck@charite.de

Principal Investigator: Marcus Beck, MD

Sub-Investigator: Sebastian Zschaeck, MD

Sub-Investigator: Peter Wust, Prof. Dr.

Sponsors and Collaborators

Charite University, Berlin, Germany

More Information

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.

• Responsible Party: Pirus Ghadjar, Head of Hyperthermia Unit, Charite University, Berlin, Germany
• ClinicalTrials.gov Identifier: NCT04159051
• Other Study ID Numbers: EA2/110/15
• First Posted: November 12, 2019
• Last Update Posted: November 12, 2019
• Last Verified: November 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Recurrence; Disease Attributes; Pathologic Processes