Metastases-directed Radiotherapy in Addition to Standard Systemic Therapy in Patients With Oligometastatic Breast Cancer (OLIGOMA)

Effectiveness and Tolerability of Metastases-directed Radiotherapy in Addition to Standard Systemic Therapy in Patients With Oligometastatic Breast Cancer: A Randomized Controlled Multinational and Multicenter Clinical Trial

The prognosis for patients with metastatic breast cancer has improved continuously. Systemic therapies alone are not able to cure the disease permanently.

Investigators initiated this randomized controlled multinational and multicenter clinical trial to analyse the impact of a local metastases-directed radiotherapy in addition to standard systemic therapy in patients with oligometastatic breast cancer on progression-free survival and quality of life.

Study Overview

• Status: Recruiting
• Conditions: Metastatic Breast Cancer
• Intervention / Treatment: Radiation: Metastases-directed Radiotherapy

Detailed Description

Preferably ablative radiotherapy (radiosurgery, stereotactic radiotherapy, hypofractionated image-guided radiotherapy (IGRT)) with few high-dose fractions. Larger lesions or lesions with critical normal tissue involvement should be treated with three-dimensional conformal radiation therapy (3D-CRT) or intensity-modulated radiation therapy (IMRT) in moderate hypofractionated radiotherapy (depending on the size and location of the target volume and the decision of the radiooncologist). For critical organs in the target volume, standard fractionated radiotherapy can be used.

• Study Type: Interventional
• Enrollment (Anticipated): 564
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Kathrin Dellas, Professor; Phone Number: 0431/500/26570; Email: Kathrin.Dellas@uksh.de

Study Locations

• Germany
  • Stendal, Germany, 39576
    • Recruiting
    • Johanniter-Krankenhaus Genthin-Stendal
    • Contact: Evelyn Weinstrauch, MD; Phone Number: 0049/3931 661504; Email: evelyn.weinstrauch@sdl.johanniter-kliniken.de
    • Contact: Sachsen-Anhalt
  • Baden-Württemberg
    • Mannheim, Baden-Württemberg, Germany, 68167
      • Recruiting
      • Universitätsmedizin Mannheim Klinik für Strahlentherapie und Radioonkologie
      • Contact: Elena Sperk, MD; Phone Number: 0049/621 383 4241; Email: elena.sperk@umm.de
  • Bayern
    • Weilheim, Bayern, Germany, 82362
      • Recruiting
      • Praxis für Strahlentherapie und Radioonkologie am Krankenhaus Weilheim
      • Contact: Monika Panzer, MD; Phone Number: 0049/88192452340; Email: mpa@strahlentherapie-weilheim.de
      • Contact: Michaela Riepl, MD; Phone Number: 0049/88192452340; Email: mrp@strahlentherapie-weilheim.de
  • Brandenburg
    • Frankfurt (Oder), Brandenburg, Germany, 15236
      • Recruiting
      • Klinikum Frankfurt (Oder) GmbH Klinik für Strahlentherapie/Radioonkologie
      • Contact: Reinhard E. Wurm, MD; Phone Number: 0049/335 548 4721; Email: reinhard.wurm@klinikumffo.de
  • Hessen
    • Marburg, Hessen, Germany, 35033
      • Recruiting
      • Universitätsklinikum Marburg Klinik für Strahlentherapie und Radioonkologie
      • Contact: Hilke Vorwerk, Prof.; Phone Number: 0049/6421 58 66270; Email: hilke.vorwerk@med.uni-marburg.de
  • Niedersachsen
    • Hameln, Niedersachsen, Germany, 31785
      • Recruiting
      • GSR Hameln im Sana Klinikum Hameln-Pyrmont
      • Contact: Stefan Janssen, MD; Phone Number: 0049/5151 9626320; Email: stefan.janssen@strahlentherapie.de
    • Hildesheim, Niedersachsen, Germany, 31135
      • Recruiting
      • Gemeinschaftspraxis für Strahlentherapie
      • Contact: Susann Popella, MD; Phone Number: 0049/5121 8942 913; Email: spopella@strahlentherapie-hildesheim.de
    • Wolfsburg, Niedersachsen, Germany, 38440
      • Recruiting
      • MVZ WOB GmbH Strahlentherapie
      • Contact: Marcel Ott, MD; Phone Number: 0049/5361 803850; Email: Marcel.Ott@Klinikum.Wolfsburg.de
  • Nordrhein-Westfalen
    • Bocholt, Nordrhein-Westfalen, Germany, 46397
      • Recruiting
      • Strahlentherapie Bocholt Gemeinschaftspraxis und Belegabteilung am St.-Agnes-Hospital
      • Contact: Eckhard Horst, MD; Phone Number: 0049/2871 246540; Email: horst@strahlentherapie-bocholt.de
    • Gelsenkirchen, Nordrhein-Westfalen, Germany, 45879
      • Recruiting
      • Evangelische Kliniken Gelsenkirchen Klinik für Strahlentherapie
      • Contact: Rodrigo Hepp, MD; Phone Number: 0049/209 160 53001; Email: heppdelosrios@evk-ge.de
  • Saarland
    • Saarlouis, Saarland, Germany, 66740
      • Recruiting
      • Xcare Praxis für Strahlentherapie Saarlouis am Marienkrankenhaus
      • Contact: Sevda Toperim; Phone Number: 0049/6831 161229; Email: sevda.toperim@x-care.de
  • Sachsen
    • Dresden, Sachsen, Germany, 01067
      • Recruiting
      • Städtisches Klinikum Dresden, Strahlentherapie
      • Contact: Andreas Schreiber, MD; Phone Number: 0049/3514803500; Email: Andreas.Schreiber@klinikum-dresden.de
      • Contact: Jörg Zimmer, MD; Phone Number: 0049/3514803501; Email: Zimmer-Jo@khdf.de
    • Zwickau, Sachsen, Germany, 08060
      • Recruiting
      • Heinrich-Braun-Klinikum Zwickau gGmbH Klinik für Strahlentherapie und Radioonkologie
      • Contact: Alexander Boicev, MD; Phone Number: 0049/375512802; Email: alexander.boicev@hbk-zwickau.de
  • Schleswig-Holstein
    • Kiel, Schleswig-Holstein, Germany, 24105
      • Recruiting
      • Christian-Albrechts-University Kiel, University Medical Center Schleswig-Holstein, Campus Kiel
      • Contact: Juergen Dunst, Prof.; Phone Number: 0049/431/50026500; Email: Juergen.Dunst@uksh.de
      • Contact: Kathrin Dellas, Prof.; Phone Number: 0049/431/50026570; Email: Kathrin.Dellas@uksh.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Metastasized breast cancer - up to 5 clinically manifest (new, progressive, persistent) metastases (a lymph node metastasis and a circumscribed local recurrence are each considered as one metastasis, i.e. also locoregional recurrent breast carcinomas with additional hematogenic metastasis possible)
• maximum of 3 cerebral metastases known
• indication for palliative drug therapy (endocrine therapy and/or chemotherapy and/or treatment with other substances) given according to guidelines (1st-line or further therapy lines, a special regime is not specified)
• Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2
• local radiation of all metastases possible
• presentation of a written declaration of consent
• patient ≥ 18 years

Exclusion Criteria:

• Previous radiotherapy, if this interferes with treatment within the scope of the study
• symptomatic metastases requiring local therapy of all metastases (e.g. pain radiation), a radiation indication (or other local therapy) for individual metastases is not a criterion for exclusion
• known central nervous system (CNS) metastasis without extracerebral metastasis (in these cases, immediate local therapy is mandatory)
• more than three known CNS metastases (no indication for purely local therapy of only the metastases, primary whole brain radiation is indicated)
• multifocal metastasis in one organ with impossibility to comply with the dose constraints for this organ (e.g., no indication for local therapy of only the metastases, primary whole brain radiation is indicated) (e.g. in the liver)
• exclusively regional lymph node metastasis without haematogenic metastases (in these cases local therapy is clearly indicated according to guidelines)
• relevant comorbidity, if this results in restrictions for further therapy
• Incapacity to contract or lack of informed consent
• Pregnancy and lactation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Standard; Standard of care, i. e. no local radiotherapy in addition to standard systemic therapy (exception: palliative local treatment of symptomatic lesions where indicated)
Experimental: Experimental; Standard of care (standard systemic therapy) + study intervention	Radiation: Metastases-directed Radiotherapy; Ablative radiotherapy (radiosurgery, stereotactic radiotherapy, hypofractionated image-guided radiotherapy (IGRT)) with few high-dose fractions

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
First co-primary outcome measure is progression-free survival (PFS)	Co-primary progression-free survival (PFS) according to Response Evaluation Criteria In Solid Tumors (RECIST)	at least 12 months after randomization
Second co-primary outcome measure is quality of life	Co-primary quality of life according to European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire for Cancer patients with 30 items (QLQ-C30) sum score	12 weeks after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility (per-protocol within intention-to-treat)	Proportion of participants treated per protocol	12 weeks
Overall survival	Time between randomization and death	at least 1, up to 5 years
Toxicity (number and degree of reported toxicities in both treatment arms)	Proportion of participants with degree of toxicities as defined by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) and by Radiation Treatment Oncology Group (RTOG) by point in time of follow-up with higher degree indicating higher intensity	0 to 5 years
Neoplasia-specific quality of life	Research and Treatment of Cancer (EORTC) Quality of Life Questionaire for Cancer patients with 30 items (QLQ-C30) with different scales	quarterly up to 5 years
Breast cancer-specific quality of life	Research and Treatment of Cancer (EORTC) Quality of Life Questionaire for breast cancer patients with 23 items (QLQ-BR23) on 4-point Likert scales with different directions	quarterly up to 5 years
Patient satisfaction	Research and Treatment of Cancer (EORTC) Patient satisfaction questionnaire for cancer patients with 33 items (PATSAT-C33) on 5-point Likert scale with higher scores indicating greater satisfaction	12 weeks
Frequency of adverse events	Number of patients with adverse and serious adverse events	0 to 5 years

Collaborators and Investigators

• Sponsor: University Hospital Schleswig-Holstein
• Investigators: Study Director: Jürgen Dunst, Professor, University Hospital Schleswig-Holstein

Publications and helpful links

General Publications

• Krug D, Vonthein R, Illen A, Olbrich D, Barkhausen J, Richter J, Klapper W, Schmalz C, Rody A, Maass N, Bauerschlag D, Hessler N, Konig IR, Dellas K, Dunst J. Metastases-directed Radiotherapy in Addition to Standard Systemic Therapy in Patients with Oligometastatic Breast Cancer: Study protocol for a randomized controlled multi-national and multi-center clinical trial (OLIGOMA). Clin Transl Radiat Oncol. 2021 Apr 5;28:90-96. doi: 10.1016/j.ctro.2021.03.012. eCollection 2021 May.

Study record dates

Study Major Dates

• Study Start (Actual): March 5, 2021
• Primary Completion (Anticipated): June 30, 2023
• Study Completion (Anticipated): June 30, 2025

Study Registration Dates

• First Submitted: June 9, 2020
• First Submitted That Met QC Criteria: July 28, 2020
• First Posted (Actual): July 31, 2020

Study Record Updates

• Last Update Posted (Actual): April 28, 2021
• Last Update Submitted That Met QC Criteria: April 27, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: Radiotherapy; Oligometastatic Breast Cancer; Progression-free survival (PFS)
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: ARO-2015-1

Drug and device information, study documents

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