Table 5.
Ongoing trials on preoperative PBI with SBRT
| ClinicalTrials.gov ID/ Study status | Inclusion criteria | Study plan | Primary/secondary endpoints | |
|---|---|---|---|---|
| Feasibility Study of Stereotactic Body Radiotherapy for Early Breast Cancer (ARTEMIS) [73] | NCT02065960/ Unknown status | Age ≥ 70 years; invasive carcinoma, G I/II, ER and PR positive, HER2 negative Stage I (T1 N0 M0) on clinical and radiological assessment with MRI of the breasts and axillary ultrasound; Candidate for BCS; | SBRT: 40 Gy in 5 fractions delivered every other day,followed by BCS |
Primary: Feasibility Secondary: Acute and late Radiation Toxicity, pCR, Ipsilateral Breast Tumour Recurrence, DFS |
| Preoperative Single-Fraction Radiotherapy in Early Stage Breast Cancer [74] | NCT02482376/ Active, not-recruiting | Age ≥ 60 years or 50–59 with a low Oncotype score (0–17); Clinical T1N0M0 invasive carcinoma or DCIS < or equal to 2cm; ER positive; HER2 negative; Candidate for BCS; | SBRT: 21Gy followed by breast conserving surgery |
Primary: Physician reported cosmesis outcomes Secondary: Ki-67 as a measure of tumor response;Patient reported cosmesis outcomes; LC; Assess the impact of RT on: gene expression, circulating cell free DNA |
| CMP-001 and Pre-operative Stereotactic Body Radiation Therapy (SBRT) in Early Stage Triple Negative Breast Cancer (TNBC) [75] | NCT04807192/ recruiting | Age ≥ 18 years; TNBC, cT1-2, at least 5 mm, cN0-1 cM0); ECOG: 0–1; planned BCS or mastectomy; No planned neoadjuvant chemotherapy/endocrine therapy or other anticancer therapy; Presence of measurable disease in the breast; Primary tumor accessible to injections and biopsy. The lesion to be injected should be confined in a single irradiation volume that does not result in more than 30% of the whole breast; The injected tumor should be located at least 5 mm from the skin or pectoral muscle |
Arm 1: SBRT: 1 × 8 Gy at D1 Arm 2: CMP-001 (4 sequential administrations of CMP001 at Day 1 (SC), Day 5 (± 1) (IT), Day 9 (± 1) (IT) and Day 16 (± 1) (IT) + SBRT 1 × 8 Gy at D1 |
Increase in sTILs, Toxicity of CMP-001 combined with SBRT, pCR, minimal residual cancer, Ki-67 levels, OS, DFS,event-free survival (EFS) |
| Study of Stereotactic Radiotherapy for Breast Cancer [76] | NCT03043794/ recruiting | Age ≥ 50 years; Invasive ductal carcinoma; T1 N0; Clearly demarcated tumor on magnetic resonance imaging (MRI); ER and/or PR ≥ 10%; HER2 negative; Candidate for BCS + SLNB; | SBRT: 21 Gy followed by standard of care surgery | RCB, pCR, treatment-related toxicity, cosmetic outcome, time to recurrence, QoL |
|
Breast Cancer Study of Stereotactic Body Radiation Therapy (SBRT) Combined Neoadjuvant Treatment (Study to Evaluate the Efficacy and Safety of Stereotactic Body Radiation Therapy (SBRT) Combined Neoadjuvant Treatment for Patients With Triple-negative and Hormone Receptor-positive, HER2-negative Breast Cancer) [23, 77 ] |
NCT05132790/ Active, not-recruiting | Age: 18–75 years; invasive adenocarcinoma of the breast; TNBC patients HER2-neu 0–1 + by IHC or FISH-negative; ER-positive and HER2-negative breast cancer; tumor ≥ 2 cm (mammogram, breast ultrasound, breast MRI); Any nodal status; ECOG 0 -1 |
Experimental: TNBC (SHR-1316 at a dose 20mg/kg q3w): Combination of SBRT and SHR1316, followed by SHR1316 plus nab-paclitaxel and carboplatin or cisplatin Experimental: HER2-/HR + BC (SHR6390 at a dose of 150mg orally, daily): SHR6390 plus exemestane with/without ovarian function suppression/ablation (OFS) after SBRT |
pCR, RCB, objective response rate (ORR), AE,serious adverse events (SAE) |
| Stereotactic Image-Guided Neoadjuvant Ablative Radiation Then Lumpectomy (SIGNAL 2) [78] | NCT02212860/ Active, not-recruiting | Age ≥ 50 years and postmenopausal; Tumor size < 3 cm; ER positive; Invasive ductal carcinoma or other favorable subtypes (lobular, medullary, papillary, colloid, mucinous, or tubular); cN0; Surgical expectation that a > 2 mm margin can be obtained; Lesion 1 cm or greater from the skin surface; surgery within 14–20 days of radiation therapy; Able to tolerate the prone position | Stereotactic image-guided neoadjuvant ablative radiation (randomized to 1 × 21 Gy or 3 × 10 Gy) followed by lumpectomy | Immune priming, angiogenesis, proliferation, apoptosis, hypoxia, invasion markers level, toxicity |
| Preoperative Stereotactic Ablative Body Radiotherapy (SABR) for Early-Stage Breast Cancer [79] |
NCT03137693/ terminated |
Age ≥ 50 years; Invasive adenocarcinoma of breast; marker clip in breast; Unifocal tumor = < 2 cm based on contrast-enhanced prone-breast MRI; cN0; candidate for BCS; Able to tolerate the prone position; target lesion at least 10 mm from skin defined on MRI; ER positive; Her-2 negative; No received or planned fof neoadjuvant chemotherapy prior to SABR or surgery; ECOG 0–2 |
SABR: 28.5 Gy in 3 fractions BCS 6–8 weeks after |
pCR |
| SABR-CaRe in Early Stage Breast Cancer [80] | NCT04959474/ recruiting | Age ≥ 40 years (with TNBC ≥ 50 years); DCIS or invasive breast cancer; BMI > = 21 at time of enrollment; KPS: 70 – 100; Tumor size = < 3.0 cm; Gross disease may be multifocal as long as the total extent of tumor, gross and microscopic, occupies a volume with greatest dimension = < 3 cm; Patient is not being considered for preoperative chemotherapy |
Arm I: standard dietary recommendations, SABR every other day for 5 fr, surgery within 4–12 weeks, surgical resection with SLNB) Arm II: caloric restriction diet, SABR every other day for 5 fr, surgery within 4–12 weeks, surgical resection with SLNB |
Percent reduction in cellularity of breast tumor |
|
Preoperative Boost Associated With Neoadjuvant Chemotherapy in Luminal B Breast Cancer IBISCO TRIAL [81] |
NCT05673304/ recruiting | Age ≥ 18 years; Luminal B BC, cT1-2; Indication for neoadjuvant chemotherapy | SBRT as an anticipated boost with a total dose of 24 Gy (8 Gy × 3 fractions QD) within 2 weeks from the start of neoadjuvant chemotherapy | pCR, acute/late toxicity |
| Three Fraction Radiation to Induce Immuno-Oncologic Response (TRIO) [82] | NCT03978663/ recruiting | Age ≥ 18 years; locally advanced breast cancer defined as stages IIB-III (excluding inflammatory breast cancer). Stage IIA is eligible for TNBC and HER2-positive breast cancers; Invasive mammary carcinoma of any subtype excluding lobular, sarcomatous, or metaplastic subtypes, or with lobular features; Plan to be treated with neoadjuvant chemotherapy; M0 | SBRT: 3 fractions administered as an anticipated boost prior to neoadjuvant chemotherapy | pCR, Immune priming, surgical wound healing, LRR |
| Neo-adjuvant Chemotherapy Combined With Stereotactic Body Radiotherapy to the Primary Tumour + /- Durvalumab, + /- Oleclumab in Luminal B Breast Cancer: (Neo-CheckRay) [83] | NCT03875573/ recruiting | Age ≥ 18 years; luminal B breast cancer subjects candidate for neo-adjuvant chemotherapy |
Arm I: Experimental: Chemotherapy and pre-operative radiation therapy (boost dose) 3 × 8 Gy Arm II: Experimental: like Arm I plus durvalumab Arm III: Experimental: like Arm I plus durvalumab plus oleclumab |
valuation of the immune related or radiation therapy related toxicity, Evaluation of the feasibility of the primary surgery, Phase II: Demonstration of the tumour response in arms 2 or 3 versus arm 1 |
|
GammaPod Dose Escalation Radiation for Early Stage Breast Cancer (GCC 1926- Phase Ib Dose Escalation of Single-Fraction Preoperative Stereotactic Partial-Breast Irradiation for Early-Stage Breast Cancer) [84] |
NCT04234386/ recruiting | Patients > 45 years; unifocal visible on a CT scan tumor; N0; ER positive; HER2 negative; invasive ductal carcinoma; candidates for BCS; Tumor must not involve the overlying skin or underlying chest wall; Greatest tumor dimension is < 3 cm based on US. MR imaging measurements can be included only if performed before the biopsy; patients weigh < 150 kg; Patients must be able to lie prone position; no lymphovascular invasion on biopsy |
single-fraction radiation dose delivered with the GammaPod as a PBI before a lumpectomy Dose Level 1: 21 Gy Dose Level 2: 24 Gy Dose Level 3: 27 Gy Dose Level 4: 30 Gy |
Establish the single-fraction radiation dose (MTD), Incidence of Dose-Limiting Toxicities (DLTs), pCR, ipsilateral LRR |
|
Single Fraction Preoperative Radiotherapy for Early Stage Breast Cancer |
NCT04679454/ recruiting | Histologically proven unifocal adenocarcinoma; T1-T2; tumor size up to 2.5 cm; cN0; Age ≥ 18 years old; ECOG 0–2; Planned BCS |
phase I dose escalation study to identify the maximum tolerated dose (MTD) delivering 18 Gy, 21 Gy and 24 Gy in single fraction phase II study to evaluate the rate of pathological complete response (pCR) when a dose level is chosen according to the results of the previous phase I study Surgical tumor removal will be scheduled after 4–8 weeks after radioablation. Whole breast radiation therapy without boost will be performed after surgery |
Identify the maximum tolerated dose (MTD), pCR, chronic toxicity, Cosmetic outcomes, Post surgery complications, DFS, Local relapse, OS, breast cancer specific survival (BCSS) |
| Single-dose Preoperative Partial Breast Irradiation in Low-risk Breast Cancer Patients (ABLATIVE-2) [86] | NCT05350722/ recruiting | WHO ≤ 2; Age ≥ 50 years; unifocal cT1N0 breast cancer on MMG, ultrasound and MRI; Patients with an indication for chemotherapy or HER2-targeted therapy are not eligible. Patients with an indication for endocrine therapy are eligible; Tumor size as assessed on MRI; grade 1–2; Non-lobular invasive histological type carcinoma; LCIS or (non-extensive) DCIS is accepted; ER positive; HER2 negative; cN0 | PBI with a single dose of 20Gy/15Gy on the GTV and CTV respectively | pCR 12 months after radiotherapy |
| A Phase I Dose Escalation Study of Single Fraction Ablative Pre-operative Partial Breast (S-PBI) for Early Stage Breast Cancer [61] | NCT04040569 /recruiting | Age > / = 18 years old; cT1-T2cN0; Tumor must be unifocal, not involve the overlying skin; must be visible on CT scan and/or preferably marked with clip(s) in tumor; ER/PR positive, Her2 negative | Preoperative single dose escalation study: 30Gy/1fr; 34Gy/1fr; 38Gy/1fr | Dose escalation studyLC, acute/late toxicity/ cosmetic outcomes |
| Phase 2 Surgical Excision vs Neoadjuvant Radiotherapy + Delayed Surgical Excision of Ductal Carcinoma (NORDIS) [87] | NCT03909282/recruiting | Core needle biopsy demonstrating DCIS; Mammographic or MRI non-mass lesion measuring 4 cm or less in greatest dimension; ER/PR positive or negative DCIS; HER2 positive, negative or unknown DCIS; biopsy marker placed within the tumor bed confirmed on post biopsy imaging and evidence of residual radiographic abnormality; Placement of Savi scout optical reflectance marker in tumor bed area as a wireless guide for surgery and for neoRT treatment planning is preferred; Planned lumpectomy. ECOG: 0, 1, or 2 |
Active Comparator: Surgical excision of ductal carcinoma Experimental: Neoadjuvant partial breast irradiation delivered once a day for 5 days before surgery. The planned daily dose is 6 Gy |
pCR correlation of DCIS subtype with pCR assessment pre and post therapy of tumor grade, atypia, necrosis |