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JOURNAL ONKOLOGIE – STUDIE
FURTHER

Focused Ultrasound and RadioTHERapy for Noninvasive Palliative Pain Treatment in Patients With Bone Metastases

Rekrutierend

NCT-Nummer:
NCT04307914

Studienbeginn:
März 2020

Letztes Update:
07.02.2024

Wirkstoff:
-

Indikation (Clinical Trials):
Neoplasms, Neoplasm Metastasis, Neoplasms, Second Primary, Bone Neoplasms, Bone Marrow Diseases

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 3

Sponsor:
UMC Utrecht

Collaborator:
Turku University Hospital, Universitätsklinikum Köln, University of Roma La Sapienza, Istituto Ortopedico Rizzoli, University of Bologna, Isala,

Kontakt

Studienlocations
(3 von 6)

University Hospital Cologne
Cologne
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Sin Yuin Yeo
E-Mail: Sin.yeo@uk-koeln.de

Holger Gruell
E-Mail: holger.gurell@uk-koeln.de» Ansprechpartner anzeigen
University Medical Center Utrecht
3508GA Utrecht
NetherlandsRekrutierend» Google-Maps
Ansprechpartner:
Helena M Verkooijen, MD, PhD
E-Mail: h.m.verkooijen@umcutrecht.nl

Renée Hovenier, MSc
E-Mail: r.hovenier-2@umcutrecht.nl» Ansprechpartner anzeigen
Isala Klinieken Zwolle
Zwolle
NetherlandsRekrutierend» Google-Maps
Ansprechpartner:
Jorik Slotman
Phone: +31 38 424 44 92
E-Mail: d.j.slotman@isala.nl

Martijn Boomsma
Phone: +31 38 424 28 82
E-Mail: M.F.Boomsma@isala.nl» Ansprechpartner anzeigen
Alle anzeigen

Studien-Informationen

Detailed Description:

Rationale: Cancer induced bone pain (CIBP) as a result of bone metastases strongly interferes

with quality of life and daily functioning of patients with advanced cancer. The current

standard of care for patients with painful bone metastasis includes palliative external beam

radiotherapy (EBRT). While EBRT is a well-established treatment option, it takes up to 4-6

weeks for EBRT to induce optimal pain relief, and 30-40% of patients do not respond to EBRT.

Pain palliation may be improved by including magnetic resonance image guided high intensity

focused ultrasound (MR-HIFU) as alternative or in addition to EBRT.

Objective: The FURTHER study aims to evaluate the effectiveness and cost-effectiveness of

MR-HIFU (alone or in combination with EBRT), as a palliative treatment option to relieve

CIBP.

Study design: The FURTHER study consists of a prospective, multicenter, three-armed

randomized controlled trial (FURTHER RCT) and a patient registry arm (FURTHER Registry),

performed in six hospitals in four European countries, all of which are partners in the

FURTHER consortium. The UMC Utrecht is coordinating center. Within the FURTHER RCT, a total

of 216 patients with painful bone metastases will be included. These patients will be

randomized in a 1:1:1 ratio to receive EBRT only, MR-HIFU only, or EBRT followed by MR-HIFU.

In the Netherlands, we expect to enroll a minimum of 70 patients, and a maximum of 120

patients in three Dutch study sites. Within the FURTHER Registry, data of around 60-90

patients will be captured.

Study population: The study will be performed in male and female adult (≥ 18 years) cancer

patients capable of giving informed consent having painful non-spinal bone metastases (pain

score on Numerical Rating Scale (NRS) ≥ 4).

Intervention: The intervention under study is MR-HIFU alone or in combination with EBRT. The

intervention is aimed at rapid and persistent relief of CIBP. In the FURTHER RCT, the

intervention will be compared to standard treatment EBRT.

Main study endpoints: Primary outcome of the study will be pain response at 14 days after the

first day of treatment. Secondary outcomes include pain response at 14 days after inclusion,

and pain scores, toxicity, adverse events, quality of life and survival in the first 6 months

after treatment, and cost-effectiveness of the treatments.

Ein-/Ausschlusskriterien

Inclusion Criteria:

- Patient capable of giving informed consent

- Age ≥ 18 years

- Painful metastatic bone lesion (NRS > 2)

- Patient-localised pain with a distinct pathological substrate on recent CT/MRI

- Target lesion location is sufficiently accessible for MR-HIFU to expect clinical

response, as judged by the (intervention) radiologist

- Participant has a reasonable performance score (KPS ≥ 50% or Zubrod/ECOG/WHO < 3)

- Life expectancy ≥ 3 months

Exclusion Criteria:

- Participant is not able to fit in the MR gantry

- Need for surgery of targeted location due to (impending) pathological fracture

- Unavoidable critical structures or dense tissues in target area

- Contra-indications for MRI or sedation/anesthesia

- Clinically relevant medical history or physical findings that could interfere with the

patient's safety as judged by the treating physician

- Participant enrolled in another clinical interventional study related to bone

metastases treatment or pain relief treatment

All patients meeting the FURTHER in- and exclusion criteria as described above will be

included in this study, either in the FURTHER RCT or FUTHER Registry. The following

inclusion criteria are used to decide upon the arm patients will participate in. If

patients meet all of the following RCT inclusion criteria, they will be asked to

participate in the FURTHER RCT. Alternatively, patients who do not meet one or more of

these criteria will be asked to participate in the FURTHER Registry.

- Painful bone lesion (NRS ≥ 4)

- Indication for EBRT treatment of a bone lesion

- Exclusively palliative intention of EBRT treatment plan

- No previous surgery on the target location

- No neurological symptoms due to nerve involvement of target lesion

- No (impending) pathological fracture)

- EBRT replacable by MR-HIFU based on medical history or phyiscal findings judged by

multidisciplinary team

- Target lesion location is completely accessible for MR-HIFU

Studien-Rationale

Primary outcome:

1. Pain response - 14 days after completion of treatment (Time Frame - 14 days):
Patient reported pain response will be based on a Numeric Rating Scale (from 0 to 10 with 0 being no pain and 10 being the worst pain imaginable) and the pain severity index calculated from the Brief Pain Inventory (BPI) questionnaire [Cleeland 1994]. In addition, analgesic and anti-neuropathic drug use is recorded, and all opioid analgesics are expressed as the oral equivalent daily morphine use (OMED). The primary endpoint of the RCT will follow the International Consensus on Palliative Radiotherapy Endpoints for Future Clinical Trials in Bone metastases (Chow 2012). Patients will be categorized as responders when a complete or partial pain response is achieved. All other patients will be categorized as non-responders.



Secondary outcome:

1. Pain response - 14 days after inclusion (Time Frame - 14 days):
Patient reported pain response will be based on a Numeric Rating Scale (from 0 to 10 with 0 being no pain and 10 being the worst pain imaginable) and the pain severity index calculated from the Brief Pain Inventory (BPI) questionnaire [Cleeland 1994]. In addition, analgesic and anti-neuropathic drug use is recorded, and all opioid analgesics are expressed as the oral equivalent daily morphine use (OMED). This endpoint will follow the International Consensus on Palliative Radiotherapy Endpoints for Future Clinical Trials in Bone metastases (Chow 2012). Patients will be categorized as responders when a complete or partial pain response is achieved. All other patients will be categorized as non-responders.

2. Patient reported pain scores - patient pain diary (Time Frame - 21 days):
Patient reported pain scores will be based on a Numeric Rating Scale (from 0 to 10 with 0 being no pain and 10 being the worst pain imaginable). This will be assessed using a daily patient pain diary during the first 21 days after completion of treatment.

3. Patient reported pain scores - BPI (Time Frame - on baseline, at 1, 2, 4 and 6 weeks, and at 3 and 6 months):
Patient reported pain scores will be based on a Numeric Rating Scale (from 0 to 10 with 0 being no pain and 10 being the worst pain imaginable). This will be assessed using the Brief Pain Inventory (BPI) questionnaire at 7 time points during the total follow up of 6 months.

4. Physician reported toxicity - CTCAE 5.0 (Time Frame - at 3 days, at 1, 2, 4 and 6 weeks, and at 3 and 6 months):
Assessed in seven telephone calls during the first six months following completion of treatment according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0

5. Patient reported quality of life - EORTC BM22 (Time Frame - on baseline, at 1, 2, 4 and 6 weeks, and at 3 and 6 months):
During the follow up time of 6 months, patients will receive the EORTC BM22 quality of life questionnaire at baseline, one, two, four and six weeks, and three and six months following completion of treatment.

6. Patient reported quality of life - EORTC C15-PAL (Time Frame - on baseline, at 1, 2, 4 and 6 weeks, and at 3 and 6 months):
During the follow up time of 6 months, patients will receive the EORTC C15-PAL quality of life questionnaire at baseline, one, two, four and six weeks, and three and six months following completion of treatment.

7. Patient reported quality of life - EQ-5D-5L (Time Frame - on baseline, at 1, 2, 4 and 6 weeks, and at 3 and 6 months):
During the follow up time of 6 months, patients will receive the EQ-5D-5L quality of life questionnaire at baseline, one, two, four and six weeks, and three and six months following completion of treatment.

8. Patient reported quality of life - PGIC (Time Frame - at 1, 2, 4 and 6 weeks, and at 3 and 6 months):
During the follow up time of 6 months, patients will receive the Patient Global Impression of Change scale (a 7 point likert scale about overall improvement after treatment) at one, two, four and six weeks, and three and six months following completion of treatment.

9. Patient reported quality of life - HADS (Time Frame - on baseline, at 1, 2, 4 and 6 weeks, and at 3 and 6 months):
During the follow up time of 6 months, patients will receive the Hospital Anxiety and Depression Scale (HADS) questionnaire at one, two, four and six weeks, and three and six months following completion of treatment. Assessed among patients, patients' partners and caregivers by the Hospital Anxiety and Depression Scale (HADS) at baseline, two and four weeks, and three and six months fol-lowing completion of treatment.

10. Local tumour control (Time Frame - 3 and 6 months):
Assessed using CT and/or MRI imaging at patient discretion at three and/or six months after completion of treatment.

11. Cost-effectiveness of the treatment (Time Frame - 6 months):
A hypothetical diagnosis related group (DRG) will be calculated from the perspective of the statutory health insurance (SHI).

Studien-Arme

  • Active Comparator: External Beam Radiotherapy
    In the control arm, patients will undergo standard radiotherapy for painful bone metastases.The radiation schedule is at the discretion of the treating radiation oncologist.
  • Experimental: MR-HIFU
    In the intervention arm, patients will be offered MR-HIFU treatment instead of standard radiotherapy. Treatment will be given following the international guidelines for MR-HIFU.
  • Experimental: Combination EBRT + MR-HIFU
    In the combination arm, patients will undergo standard radiotherapy followed by MR-HIFU in a short timeframe.

Geprüfte Regime

  • External beam radiotherapy:
    The current standard of care for patients with uncomplicated painful bone metastases is palliative locoregional external beam radiotherapy, often in combination with systemic therapy and analgesics.
  • MR-HIFU (MRgFUS / MR guided High Intensity Focused Ultrasound / ):
    MR-HIFU is a non-invasive treatment modality that delivers acoustic energy to heat tissue to ablative temperatures of more than 60°C. The combination of focused ultrasound with magnetic resonance imaging (MRI) enables physicians to perform localized tumor tissue ablation, with real-time temperature monitoring using magnetic resonance (MR) thermometry.

Quelle: ClinicalTrials.gov


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