Stereotactic Ablative Body Radiotherapy (SABR) With Maintenance of Systemic Therapy Versus Physicians' Choice of Systemic Therapy for Oligoprogressive ER-positive, Her-2 Negative Breast Cancer II

Обзор

The goal of this clinical trial is to assess Stereotactic Ablative Radiotherapy (SABR) as a method to delay a change in systemic therapy in patients with oligoprogressive ER-positive, HER2-negative advanced breast cancer. The main question it aims to answer is to assess whether the addition of SABR to continuation of first line endocrine therapy and CDK 4/6 inhibitor (Arm A) to patients with oligoprogressive ER-positive, HER2-negative advanced breast cancer could have longer time to strategy failure (TSF) in comparison to physician choice of systemic treatment (Arm B) in patients who had progressed first line. The treatment strategy in Arm A is to maintain patients on current endocrine therapy and CDK 4/6 inhibitor, controlling localised progressing sites of disease with SABR. Treatment strategy in Arm B is to maintain disease control with physician's choice of systemic therapy alone.

Подробное описание

AVATAR II is a phase II multicentre open label, randomised trial. Following informed consent, eligible patients with ER-positive, HER2-negative advanced breast cancer receiving an ET (either AI or selective estrogen receptor degrader in combination with a CDK 4/6 inhibitor with newly diagnosed OPD amenable to SABR will be randomised to either:

Arm A: SABR to all known sites of OPD with continuation of first line therapy ET and CDK 4/6 inhibitor Arm B: Physician's choice of systemic treatment

Patients must have evidence of radiological response to ET and CDK 4/6 inhibitor for a minimum of six months prior to randomisation (defined as either stable disease or partial response).

All patients will be followed up for 3 years after the last patient has been randomised.

Вмешательства

• Лучевая терапия Stereotactic Ablative Radiotherapy
  Stereotactic Ablative Radiotherapy
• Другое Physician's choice of systemic treatment
  Physician's choice of systemic therapy does not mandate a change in systemic therapy, however, SABR is not permitted for management in this arm

Первичные конечные точки

• Primary Outcome Measure [Срок оценки: Time from randomisation to progression of disease resulting in a failure of treatment strategy or death by any cause assessed until withdrawal of consent, death, or 3 years after the last patient has been randomised, whichever is earlier.]

Вторичные конечные точки (6)

• Secondary Objective 1 [Срок оценки: Time from randomisation to progression of disease resulting in a failure of treatment strategy or death by any cause assessed until withdrawal of consent, death, or 3 years after the last patient has been randomised, whichever is earlier.]
• Secondary Objective 2 [Срок оценки: Time from randomisation to progression of disease resulting in a failure of treatment strategy or death by any cause assessed until withdrawal of consent, death, or 3 years after the last patient has been randomised, whichever is earlier.]
• Secondary Objective 3 [Срок оценки: Time from randomisation to progression of disease resulting in a failure of treatment strategy or death by any cause assessed until withdrawal of consent, death, or 3 years after the last patient has been randomised, whichever is earlier.]
• Secondary Objective 4 [Срок оценки: Time from randomisation to progression of disease resulting in a failure of treatment strategy or death by any cause assessed until withdrawal of consent, death, or 3 years after the last patient has been randomised, whichever is earlier.]
• Secondary Objective 5 [Срок оценки: Time from randomisation to progression of disease resulting in a failure of treatment strategy or death by any cause assessed until withdrawal of consent, death, or 3 years after the last patient has been randomised, whichever is earlier.]
• Secondary Objective 6 [Срок оценки: Time from randomisation to progression of disease resulting in a failure of treatment strategy or death by any cause assessed until withdrawal of consent, death, or 3 years after the last patient has been randomised, whichever is earlier.]

Критерии участия

Критерии включения

Patients will be eligible for inclusion in this trial if all the following criteria apply:

• Patient has signed the AVATAR-II Patient Information and Consent Form (PICF)
• Male or female, ≥ 18 years of age at the time signing consent
• Patients with histologically proven ER-positive, HER2-negative advanced breast cancer receiving an ET in combination with a CDK 4/6 inhibitor. Biopsy of metastatic disease if technically feasible but not mandatory
• Patients must have evidence of extracranial metastatic disease, with no evidence of uncontrolled intracranial metastases. (Controlled intracranial metastases are defined as stable disease on repeat CT imaging performed at least one month apart.)
• Patients must have evidence of radiological response to ET and CDK 4/6 inhibitor for a minimum of six months prior to randomisation (defined as either stable disease or partial response).

Note: Patient must have ongoing stability/response in at least one lesion at the time of randomisation.

• Evidence of new or existing OPD, as determined by the Investigator and defined according to RECIST1.1 (33), via CT on a per-lesion basis (between 1-5 metastases, including the primary) as follows:

• At least a 20% increase in the diameter of a lesion, taking as reference the smallest diameter on a previous CT scan with an absolute increase of at least 5mm
• Appearance of a new lesion(s) Note: A new lesion can be identified using various imaging modalities, such as PET-CT or WBBS, as long as the lesion is visible on serial CT scans.
• For patients with liver or lung metastases, maximum of 3 oligoprogressive lesions in single organ
• All OPD must be amenable to SABR, as per the radiotherapy guidelines in section 11.1 and Appendix 4 and 5
• ECOG performance status 0-2
• Life expectancy ≥ 6 months
• Clinician and patient are willing to continue current line of therapy
• Patient is able to complete QoL questionnaires, and other assessments required as part of the study

Критерии исключения

Patients will not be eligible for inclusion in this trial if any of the following criteria apply:

• Is pregnant or lactating at the time of randomisation
• Evidence of more than one clone of metastatic disease e.g., a patient with both ER-positive and triple negative clones of disease And ER-negative and/or HER2-positive disease would be excluded from the study
• Evidence of leptomeningeal disease
• Evidence of malignant cord compression
• Evidence of lesion within femoral bone requiring surgical fixation
• Patients with risk of bone fracture are not candidate for SABR (Appendix 4 and 5)
• Previous chemotherapy for metastatic disease Note: chemotherapy for primary breast cancer is allowed
• Contraindications to radiotherapy
• Any condition deeming the patient unsuitable to comply with the study
• Substantial overlap with previously treated area. Reirradiation is permitted with the condition that the combined plan adheres to the specific dose constraints outlined in this protocol. It is advised to use biological effective dose (BED) calculations to correlate previous doses with the tolerance doses documented in the protocol
• Evidence of progression in more than 5 lesions
• Prior SABR delivered for oligoprogressive disease with the intent of delaying a change in systemic therapy.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Публикации

• Alomran R, White M, Bruce M, Bressel M, Roache S, Karroum L, Hanna GG, Siva S, Goel S, David S. Stereotactic radiotherapy for oligoprogressive ER-positive breast cancer (AVATAR). BMC Cancer. 2021 Mar 23;21(1):303. doi: 10.1186/s12885-021-08042-w. PMID 33757458
• David SP, Siva S, Bressel M, Tan J, Hanna GG, Alomran RK, et al. Stereotactic Ablative Body Radiotherapy (SABR) for Oligoprogressive ER-Positive Breast Cancer (AVATAR): A Phase II Prospective Multicenter Trial. International journal of radiation oncology, biology, physics. 2023;117(4):e6-e.
• Kelly P, Ma Z, Baidas S, Moroose R, Shah N, Dagan R, Mamounas E, Rineer J. Patterns of Progression in Metastatic Estrogen Receptor Positive Breast Cancer: An Argument for Local Therapy. Int J Breast Cancer. 2017;2017:1367159. doi: 10.1155/2017/1367159. Epub 2017 Sep 25. PMID 29147583
• Patel PH, Palma D, McDonald F, Tree AC. The Dandelion Dilemma Revisited for Oligoprogression: Treat the Whole Lawn or Weed Selectively? Clin Oncol (R Coll Radiol). 2019 Dec;31(12):824-833. doi: 10.1016/j.clon.2019.05.015. Epub 2019 Jun 8. PMID 31182289
• Cheung P. Stereotactic body radiotherapy for oligoprogressive cancer. Br J Radiol. 2016 Oct;89(1066):20160251. doi: 10.1259/bjr.20160251. Epub 2016 Aug 24. PMID 27556349
• Chan OSH, Lee VHF, Mok TSK, Mo F, Chang ATY, Yeung RMW. The Role of Radiotherapy in Epidermal Growth Factor Receptor Mutation-positive Patients with Oligoprogression: A Matched-cohort Analysis. Clin Oncol (R Coll Radiol). 2017 Sep;29(9):568-575. doi: 10.1016/j.clon.2017.04.035. Epub 2017 May 9. PMID 28499791
• Weickhardt AJ, Scheier B, Burke JM, Gan G, Lu X, Bunn PA Jr, Aisner DL, Gaspar LE, Kavanagh BD, Doebele RC, Camidge DR. Local ablative therapy of oligoprogressive disease prolongs disease control by tyrosine kinase inhibitors in oncogene-addicted non-small-cell lung cancer. J Thorac Oncol. 2012 Dec;7(12):1807-1814. doi: 10.1097/JTO.0b013e3182745948. PMID 23154552
• Xu Q, Liu H, Meng S, Jiang T, Li X, Liang S, Ren S, Zhou C. First-line continual EGFR-TKI plus local ablative therapy demonstrated survival benefit in EGFR-mutant NSCLC patients with oligoprogressive disease. J Cancer. 2019 Jan 1;10(2):522-529. doi: 10.7150/jca.26494. eCollection 2019. PMID 30719148

Идентификаторы

NCT: NCT06882499 · PMC105165 (24/143)

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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