Stereotactic Ablative Radiotherapy for OligoMetastatic Breast Cancer (TAORMINA)

Treatment of Oligometastatic Breast Cancer - a Randomised Phase 3 Trial Comparing Stereotactic Ablative Radiotherapy and Systemic Treatment With Systemic Treatment Alone as 1st Line Treatment

TAORMINA is an international, multicentre, randomised phase 3 trial for patients with oligometastatic breast cancer (OMBC) that will be allocated to combined stereotactic ablative radiotherapy (SABR) + systemic therapy (investigational arm) versus systemic therapy alone (control arm) as 1st line therapy.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer Stage IV; Oligometastatic Disease
• Intervention / Treatment: Radiation: SABR

Detailed Description

TAORMINA is an international, multicentre, randomised phase 3 trial for patients with oligometastatic breast cancer (OMBC) that will be allocated to combined stereotactic ablative radiotherapy (SABR) + systemic therapy (investigational arm) versus systemic therapy alone (control arm) as 1st line therapy.

Patients with 1-5 metastases in 1-2 organs (confirmed by PET-CT) with any breast cancer subtype can be enrolled. All metastases must be available for SABR.

The primary aim is to investigate if the addition of SABR to the oligometastatic sites in addition to the standard first-line treatment can improve progression-free survival (PFS).

Secondary aims are to compare overall survival (OS), response rate and time to development of new lesions, acute and late toxicity. quality of life, time to start of chemotherapy (luminal patients).

Exploratory analyses:

Circulating tumour DNA as an early sign of disease progression. Immun panel for determination of the effect of SABR on patients´ immune response.

To investigate the survival for each BC subtype (Luminal, HER2+ and TNBC). To investigate survival in patients with de novo OMBC and recurrent OMBC respectively.

Stratifications are based on subtype (luminal, HER2-positive vs TNBC) and type of OMBC (de novo vs. recurrent) without formal sample size calculation for the stratification factor (exploratory analysis).

Patients with de novo metastatic OMBC that is planned for neoadjuvant treatment are recommended to complete treatment followed by standard surgery and radiotherapy or SABR towards the primary tumour lesion(s).

• Study Type: Interventional
• Enrollment (Anticipated): 345
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Katarzyna Kulbacka-Ortiz, CTO; Phone Number: +46721470685; Email: katarzyna.kulbacka-ortiz@vgregion.se
• Study Contact Backup: Name: Annika Baan; Phone Number: +46700906097; Email: annika.baan@vgregion.se

Study Locations

• Sweden
  • Västra Götalandsregionen
    • Gothenburg, Västra Götalandsregionen, Sweden, 41345
      • Recruiting
      • Sahlgrenska University Hospital
      • Contact: Barbro Kristina Linderholm, P.I.; Phone Number: 0313427941; Email: barbro.linderholm@oncology.gu.se

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Histologically or cytological confirmed recurrent OMBC.
2. Age ≥18 years old.
3. OMBC defined as 1-5 metastases in a maximum of two organs confirmed by PET-CT.
4. Patients already on 1st line systemic treatment can be enrolled if repeated tumour evaluations show stable disease.
5. Patients with de novo stage IV OMBC must have a controlled primary tumour regardless of primary surgery or primary systemic treatment.
6. Patients with local recurrence and OMBC must have a controlled local recurrence.
7. ECOG/WHO 0-2.
8. Life expectancy > 6 months.
9. Known ER, PgR and HER2 status of either primary tumour or metastasis (preferred).
10. If measurable lesions, each ≤ 5 cm.
11. Symptomatic bone metastases are allowed if ablative therapy can be delivered (femoral metastasis not allowed).
12. Adequate organ function for the planned treatment according to local guide-lines.

13. For patients with liver metastasis:

    • No cirrhosis or hepatitis

    • Hepatic function:

      • Total bilirubin level < 3.0 x institutional ULN
      • ALT, AST, GGT, and alkaline phosphatase levels < 3.0 x institutional ULN
      • Albumin > 2.5 mg/dL
    • Metastasis not adjutant to stomach or small bowel.
14. For patients with abdominal metastases: adequate renal function with a calculated creatinine clearance of > 60mL/min.
15. Toxicities from previous adjuvant therapies (excluding alopecia) must have recovered to grade 1 (defined by CTCAE 5.0). Stable grade 2 peripheral neuropathy are considered individually by the investigator.
16. Negative pregnancy test within 14 days prior to start of treatment*.
17. If childbearing potential, willing to use an effective form of contraception*.
18. No other malignancy during the last 5 years except for radically treated basal or squamous cell carcinoma of the skin or CIS of the cervix.
19. Signed informed consent and willingness to follow the trial procedures.

Exclusion Criteria:

1. > 1 line of systemic treatment for OMBC due to previous progressing disease (previous treatment of isolated local recurrences with a 2nd adjuvant treatment not included).
2. Oligometastases in brain.
3. Malignant pleural effusion or ascites.
4. Metastasis growth that involves > 3 vertebra and adjacent spinal cord, spine instability or neurological deficit resulting from compression, 25% spinal canal compromise or progressive neurological deficit.
5. Unable to undergo imaging by either CT scan or MRI.
6. Evidence of any other medical conditions (such as psychiatric illness, infectious diseases, neurological conditions, physical examination or laboratory findings) that may interfere with the planned treatment or affect patient compliance.
7. Pregnancy or breast-feeding.
8. Concurrent malignancy requiring therapy (excluding non-invasive carcinoma or carcinoma in situ).

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
Experimental: Experimental SABR arm; Standard first line systemic therapy + SABR.	Radiation: SABR; Stereotactic Ablative Radiotherapy is delivered to all metastatic lesions.
No Intervention: Control systemic therapy arm; Standard first line systemic therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)	Time from the date of randomisation to the date of disease-progression at any site or death from any cause.	3 years after the last patient inclusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	Time from the date of randomisation to the date of death from any cause.	3 years after the last patient inclusion
Local Control Rate (LCR)	Time from the date of randomisation to the date of progress in previously treated metastases	3 years after the last patient inclusion
Safety analysis - acute toxicity	Reported according to CTCAE v.5.0	From the first dose of SABR to 3 months after the last dose of SABR
Safety analysis - late toxicity	Reported according to CTCAE v.5.0	From the first dose of SABR to 3 years after the last dose of SABR
Health-related quality of life Cancer-30	European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaires Cancer-30 (EORTC-QLQ C30)	At base-line and after 3, 6, 9, 12, 18, 24 and 36 months after registration.
Health-related quality of life Breast-23	European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire Breast-23 (EORTC-QLQ B23)	At base-line and after 3, 6, 9, 12, 18, 24 and 36 months after registration.

Collaborators and Investigators

• Sponsor: Vastra Gotaland Region
• Collaborators: Karolinska University Hospital; Oslo University Hospital; University Hospital of North Norway; Sahlgrenska University Hospital, Sweden; Haukeland University Hospital; St. Olavs Hospital; Sundsvall Hospital; Skane University Hospital; Karlstad Central Hospital; University Hospital, Umeå; Region Örebro County; Uppsala University Hospital; Azienda Ospedaliero-Universitaria Careggi; Gävle Hospital; University of Stavanger; Centrallasarettet Västerås
• Investigators: Principal Investigator: Barbro K Linderholm, MD, PhD, Sahlgrenska University Hospital, Gothenburg

Publications and helpful links

General Publications

• Milano MT, Zhang H, Metcalfe SK, Muhs AG, Okunieff P. Oligometastatic breast cancer treated with curative-intent stereotactic body radiation therapy. Breast Cancer Res Treat. 2009 Jun;115(3):601-8. doi: 10.1007/s10549-008-0157-4. Epub 2008 Aug 22.
• Milano MT, Katz AW, Zhang H, Okunieff P. Oligometastases treated with stereotactic body radiotherapy: long-term follow-up of prospective study. Int J Radiat Oncol Biol Phys. 2012 Jul 1;83(3):878-86. doi: 10.1016/j.ijrobp.2011.08.036. Epub 2011 Dec 13.
• Scorsetti M, Franceschini D, De Rose F, Comito T, Villa E, Iftode C, Navarria P, D'Agostino GR, Masci G, Torrisi R, Testori A, Tinterri C, Santoro A. Stereotactic body radiation therapy: A promising chance for oligometastatic breast cancer. Breast. 2016 Apr;26:11-7. doi: 10.1016/j.breast.2015.12.002. Epub 2016 Jan 3.
• Milano MT, Katz AW, Zhang H, Huggins CF, Aujla KS, Okunieff P. Oligometastatic breast cancer treated with hypofractionated stereotactic radiotherapy: Some patients survive longer than a decade. Radiother Oncol. 2019 Feb;131:45-51. doi: 10.1016/j.radonc.2018.11.022. Epub 2018 Dec 28.
• Trovo M, Furlan C, Polesel J, Fiorica F, Arcangeli S, Giaj-Levra N, Alongi F, Del Conte A, Militello L, Muraro E, Martorelli D, Spazzapan S, Berretta M. Radical radiation therapy for oligometastatic breast cancer: Results of a prospective phase II trial. Radiother Oncol. 2018 Jan;126(1):177-180. doi: 10.1016/j.radonc.2017.08.032. Epub 2017 Sep 21.
• David S, Tan J, Savas P, Bressel M, Kelly D, Foroudi F, Loi S, Siva S. Stereotactic ablative body radiotherapy (SABR) for bone only oligometastatic breast cancer: A prospective clinical trial. Breast. 2020 Feb;49:55-62. doi: 10.1016/j.breast.2019.10.016. Epub 2019 Nov 6.
• Li MP, Kelly D, Tan J, Siva S, Kron T, David S. Single-fraction stereotactic ablative body radiotherapy for sternal metastases in oligometastatic breast cancer: Technique and single institution experience. J Med Imaging Radiat Oncol. 2020 Aug;64(4):580-585. doi: 10.1111/1754-9485.13075. Epub 2020 Jun 25.
• Palma DA, Olson R, Harrow S, Gaede S, Louie AV, Haasbeek C, Mulroy L, Lock M, Rodrigues GB, Yaremko BP, Schellenberg D, Ahmad B, Senthi S, Swaminath A, Kopek N, Liu M, Moore K, Currie S, Schlijper R, Bauman GS, Laba J, Qu XM, Warner A, Senan S. Stereotactic Ablative Radiotherapy for the Comprehensive Treatment of Oligometastatic Cancers: Long-Term Results of the SABR-COMET Phase II Randomized Trial. J Clin Oncol. 2020 Sep 1;38(25):2830-2838. doi: 10.1200/JCO.20.00818. Epub 2020 Jun 2.

Study record dates

Study Major Dates

• Study Start (Actual): September 19, 2022
• Primary Completion (Anticipated): December 31, 2025
• Study Completion (Anticipated): December 31, 2027

Study Registration Dates

• First Submitted: April 11, 2022
• First Submitted That Met QC Criteria: May 11, 2022
• First Posted (Actual): May 17, 2022

Study Record Updates

• Last Update Posted (Actual): October 21, 2022
• Last Update Submitted That Met QC Criteria: October 18, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: SABO 21-01

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