Treatment of Advanced Castration Resistant Prostate Carcinoma With Limited Bone Metastases (α-RT)

NCT ID: NCT02484339

Last Updated: 2016-04-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

274 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-12-31

Study Completion Date

2017-12-31

Brief Summary

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Phase II open-label study to evaluate the efficacy and safety of Radium-223 dichloride in combination with external beam radiotherapy (EBRT) vs. external beam radiotherapy alone in the treatment of advanced castration resistant prostate carcinoma with limited bone metastases.

To evaluate if time to radiological progression according to the "Recommendations of the Prostate Cancer Clinical Trials Working Group" published by Scher et al. (JCO 2008) (based on new lesions in bone scan and CT /MRI or death) of Radium-223 dichloride combined with EBRT is superior compared to EBRT alone.

Detailed Description

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This is an international, multi-center, open-label, prospective, phase II study designed to assess the efficacy of radiation therapy in combination with Radium-223 dichloride in patients diagnosed with CRPC and oligo metastases bone disease. All patients enrolled in this study will have signed an informed consent form (ICF) and will adhere to all inclusion and exclusion criteria.

During the treatment period, patients will be followed on an ongoing basis for safety and quality of life (QoL). Safety assessments will include the collection of all AEs of any grade, serious adverse events (SAEs), adverse event (AEs) corresponding to symptoms arising from bone metastases, laboratory values, (WHO/ECOG) performance status (PS). Documentation of the date of disease progression will be performed at intervals and imaging methods (bone scans and CR/MRI) described in the study protocol. Quality of life will be measured by patient assessment using a validated questionnaire, the Brief Pain Inventory Short Form (BPI-SF), the European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ)-C15-PAL and the EORTC QLQ- Bone Metastases (BM) 22. Follow-up assessments for safety AEs and SAEs, and the occurrence of secondary malignancies will be conducted every 3-12 months until the patient dies or until the study is terminated by the sponsor. If the patient can no longer travel to the clinical site, he will be followed up for survival only, i.e., the long term follow-up phase of the study.

Conditions

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Prostate Carcinoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Treatment Group A

Radium-223 dichloride (Xofigo®) 55 kilobecquerel (kBq)/kgbw (6 i.v. injections every 4 weeks)

External beam radiotherapy (EBRT)-\>conventional or high dose radiotherapy

Group Type EXPERIMENTAL

Radium-223 dichloride

Intervention Type DRUG

Arm A: EBRT and timely sequential start with Radium-223 dichloride 55 kBq/kgbw (6 i.v. injections every 4 weeks) and best supportive care until progression or intolerable toxicity.

Conventional or high dose radiotherapy

Intervention Type OTHER

Arm B: External beam radiotherapy (EBRT)-\>-\>conventional or high dose radiotherapy

Treatment Group B

External beam radiotherapy (EBRT) -\>conventional or high dose radiotherapy

Group Type OTHER

Conventional or high dose radiotherapy

Intervention Type OTHER

Arm B: External beam radiotherapy (EBRT)-\>-\>conventional or high dose radiotherapy

Interventions

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Radium-223 dichloride

Arm A: EBRT and timely sequential start with Radium-223 dichloride 55 kBq/kgbw (6 i.v. injections every 4 weeks) and best supportive care until progression or intolerable toxicity.

Intervention Type DRUG

Conventional or high dose radiotherapy

Arm B: External beam radiotherapy (EBRT)-\>-\>conventional or high dose radiotherapy

Intervention Type OTHER

Other Intervention Names

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Xofigo® External beam radiotherapy (EBRT)

Eligibility Criteria

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Inclusion Criteria

1. Has provided written informed consent. Subjects must be able to understand and be willing to sign the written informed consent form (ICF). Age ≥ 18 and ≤ 85 years
2. Patients with progressive castration resistant prostate cancer (CRPC) with 1-5 bone metastases for whom Radium-223 dichloride constitutes first-line cytostatic treatment
3. Primary tumor (and its local recurrence, if applicable) controlled by effective local treatment
4. If diagnosed, pelvic lymph node metastases controlled by effective local treatment
5. At least 1 not previously locally treated skeletal metastasis on bone scan without non-bone distant metastases (e.g. lung, liver, and/or brain metastases) and without pathologically enlarged lymph nodes above the pelvis
6. Progressive disease is defined either by:

* The appearance of new bone lesions. If progression is based on new lesion(s) on bone scan only without an increase in prostate specific antigen (PSA), PSA values from 3 assessments within the last 6 months must be provided; OR
* In the absence of new bone lesions by 2 consecutive increases in serum PSA over previous reference value, which should not be more than 6 months before screening, each measured at least 1 week apart with the last PSA ≥5 ng/mL
7. Life expectancy of at least 6 months.
8. (WHO/ECOG) Performance Status (PS) 0 or 1
9. Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to start of therapy:
10. Patient has or has had symptoms (e. g. pain or micro)

Exclusion Criteria

Excluded medical conditions:

1. More than 5 not previously locally treated bone metastases as diagnosed by bone scintigraphy;
2. Visceral or lymph node metastases above the pelvis as assessed by computed tomography (CT) (or other imaging modality) ;
3. History of HIV infection or chronic hepatitis B or C
4. Active clinically serious infections (\> grade 2 National Cancer Institute Common Terminology Criteria (NCI-CTC) version 4.03)
5. History of organ allograft
6. Patients undergoing renal dialysis
7. Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study if not in complete remission for at least 5 years since date of diagnosis treated treated basal cell carcinoma, superficial bladder tumors \[Ta, Tis \& T1\] or any cancer curatively treated \> 3 years prior to study entry.
8. Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results
9. Imminent or history of spinal cord compression based on clinical findings and/or magnetic resonance imaging (MRI)
10. Any other serious illness or medical condition
11. Fecal incontinence
12. Any condition that is unstable or could jeopardize the safety of the patient and his compliance in the study
13. Known allergy to Radium-223 dichloride (i.e. to active substance or one of the constituents)

Excluded therapies and medications, previous and concomitant:

1. Anticancer chemo- or targeted therapy for CRPC
2. Radiotherapy for prostate cancer manifestations other than study treatment if not given with curative intent to prostate fossa and/or pelvic lymph nodes
3. Major surgery within 4 weeks of study entry.
4. Systemic therapy with radionuclides for the treatment of bone metastases
5. Autologous bone marrow transplant or stem cell rescue within 4 months of study entry
6. Use of biologic response modifiers, such as Granulocyte-Colony Stimulating Factor (G-CSF), within 3 week of study entry
7. Investigational drug therapy outside of this trial during or within 4 weeks of study entry
Minimum Eligible Age

18 Years

Maximum Eligible Age

85 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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University Hospital Freiburg

OTHER

Sponsor Role lead

Responsible Party

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Prof. Dr. Ursula Nestle

Prof.Dr. med

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Ursula Nestle

Role: PRINCIPAL_INVESTIGATOR

University Hospital Freiburg, Germany

Locations

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Universitätsklinikum "Carl Gustav Carus" der Technischen Universität Dresden

Dresden, , Germany

Site Status RECRUITING

Universitätsklinikum Freiburg, Klinik für Strahlenheilkunde

Freiburg im Breisgau, , Germany

Site Status RECRUITING

Universitätsmedizin Mainz, Klinik und Poliklinik für Nuklearmedizin

Mainz, , Germany

Site Status RECRUITING

Klinikum der Universität München

München, , Germany

Site Status RECRUITING

Universitätsklinikum Tübingen

Tübingen, , Germany

Site Status RECRUITING

Universitätsklinikum Würzburg

Würzburg, , Germany

Site Status RECRUITING

Countries

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Germany

Central Contacts

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Ursula Nestle, Prof.Dr.

Role: CONTACT

Daniel Schnell, Dr.

Role: CONTACT

Facility Contacts

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Tobias Hölscher, Dr

Role: primary

0351 4580

Franziska Hessel, Dr

Role: backup

0351 4580

Ursula Nestle, Prof.Dr.

Role: primary

Daniel Schnell, Dr.

Role: backup

Matthias Miederer, Prof.

Role: primary

06131 170

Mathias Schreckenberger, Prof.

Role: backup

06131 170

Ute Ganswindt, Prof

Role: primary

089 / 4400-0

Minglun Li, Dr

Role: backup

089 / 4400-0

Arndt Ch Müller, Prof

Role: primary

07071 290

Daniel Zips, Prof

Role: backup

07071 290

Andreas K Buck, Prof

Role: primary

0931 2010

Ken Herrmann, PD

Role: backup

0931 2010

Other Identifiers

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α-RT

Identifier Type: -

Identifier Source: org_study_id

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