Clinical Trials/NCT03464942

NCT03464942

Completed

Phase 2

A Randomised Phase II Trial Comparing the Efficacy of Single-fraction or Multi-fraction SABR (Stereotactic Ablative Body Radiotherapy) With AteZolizumab in Patients With Advanced Triple nEgative Breast Cancer

Peter MacCallum Cancer Centre, Australia1 site in 1 country54 target enrollmentAugust 1, 2018

ConditionsBreast Cancer

InterventionsSABR Atezolizumab

DrugsAtezolizumab

Overview

Phase: Phase 2
Intervention: SABR
Conditions: Breast Cancer
Sponsor: Peter MacCallum Cancer Centre, Australia
Enrollment: 54
Locations: 1
Primary Endpoint: Progression Free Survival
Status: Completed
Last Updated: 2 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This is a multi-centre, open label, phase 2, randomised controlled trial of patients with advanced triple negative breast cancer (TNBC) who have received no more than one line of chemotherapy (not including neoadjuvant or adjuvant therapy) who will be randomised to be treated with SABR 20Gy in 1# followed by atezolizumab or SABR 24Gy in 3# followed by atezolizumab.

Registry

clinicaltrials.gov

Start Date

August 1, 2018

End Date

June 22, 2023

Last Updated

2 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Peter MacCallum Cancer Centre, Australia

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Participants with a histological or cytological diagnosis of Stage IV TNBC breast cancer (see Appendix 7), defined by ER \<1%, PR \<1% and HER2 negative on IHC and/or non-amplified by ISH by local lab testing.
•Written informed consent.
•Male or female participants aged ≥ 18 years and \< 70 years.
•No more than one prior chemotherapy line in the incurable disease setting. For the purposes of this trial, adjuvant or neoadjuvant chemotherapy does not count as a prior line of therapy but chemotherapy given for residual disease post neoadjuvant chemotherapy is considered as one line.
•Must be 6 or more months from prior adjuvant, neoadjuvant or post neoadjuvant chemotherapy last dose.
•At least one measurable lesion as per RECIST 1.1 (see Appendix 1) that is not planned to receive SABR.
•CT scan (CAP), while body bone scan, and FDG-PET scan evidence of ≥ 2 metastases (with ≥ 1 amenable to SABR).
•Be willing to provide tissue from a newly obtained core biopsy of a metastatic tumour lesion. Newly-obtained is defined as a specimen obtained up to 60 days prior to randomisation. Patients for whom newly-obtained samples cannot be provided (e.g. inaccessible or patient safety concern) may submit an archived specimen only upon agreement from the CPI).
•ECOG performance status 0 - 1 (see Appendix 6).
•Expected life expectancy \> 6 months.

Exclusion Criteria

•Previous radiotherapy (BED \> 30Gy) to an area to be treated.
•Evidence of active brain metastases. Participants with previously treated brain metastases (with surgical resection, stereotactic radiosurgery or palliative whole brain radiotherapy) may participate, provided they have stable brain metastases defined as 2 imaging studies documenting stability of brain metastasis(es) over \> 4 weeks.
•Intention to treat or requirement for treatment with any chemotherapy agent within ± 3 weeks of trial treatment.
•Note: bisphosphonates or RANKL inhibitors are allowed.
•Evidence of Spinal Cord Compression.
•Spinal Instability Neoplastic Score ≥ 7 (see Appendix 4), in a lesion scheduled for SABR treatment unless lesion reviewed by a neurosurgical service and considered stable.
•Untreated lytic metastases in the neck of the femur that erodes the cortex that is scheduled for SABR treatment.
•Is currently participating and receiving trial therapy or has participated in a trial of an investigational agent and is planned to receive trial therapy or used an investigational device within 4 weeks of trial treatment
•Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (\> or equal to 10mg prednisolone daily) or any other form of immunosuppressive therapy at time of trial treatment. Note: There must be no intention to commence systemic long-term steroid therapy or any form of immunosuppressive therapy within 7 days prior to the planned first dose of atezolizumab treatment. Note: Single (once off) doses of prophylactic steroid therapy are acceptable.
•Is planned to receive chemotherapy, targeted small molecule therapy, or radiation therapy within 3 weeks prior to trial treatment or who has not recovered from adverse events (i.e. AEs not at ≤ Grade 1 or at baseline values) due to a previously administered agent.

Arms & Interventions

Single Dose

SABR 20Gy given as a single dose (to 1 -4 metastases with at least 1 untreated metastasis) followed by atezolizumab (1200 mg) every 3 weeks for 24 months.

Intervention: SABR

Single Dose

SABR 20Gy given as a single dose (to 1 -4 metastases with at least 1 untreated metastasis) followed by atezolizumab (1200 mg) every 3 weeks for 24 months.

Intervention: Atezolizumab

Fractionated Dose

SABR 24Gy given as 3 fractions (to 1 -4 metastases with at least 1 untreated metastasis) followed by atezolizumab (1200 mg) every 3 weeks for 24 months.

Intervention: SABR

Fractionated Dose

SABR 24Gy given as 3 fractions (to 1 -4 metastases with at least 1 untreated metastasis) followed by atezolizumab (1200 mg) every 3 weeks for 24 months.

Intervention: Atezolizumab

Outcomes

Primary Outcomes

Progression Free Survival

Time Frame: 24 months

To assess the progression free survival of SABR at a dose of 24Gy in 3# followed by atezolizumab and SABR at a dose of 20Gy in 1# followed by atezolizumab in patients with advanced triple negative breast cancer (TNBC).

Secondary Outcomes

Incidence of treatment emergent adverse events (safety and tolerability)(24 months)
Time to Treatment Failure between different SABR regimens + atezolizumab(24 months)
Progression Free Survival Comparison between different SABR regimens + atezolizumab(24 Months)
Best Objective Response (BOR) between different SABR regimens + atezolizumab(24 months)
Duration of Response (DOR) between different SABR regimens + atezolizumab(24 months)
Disease Control Rate (DCR) between different SABR regimens + atezolizumab(24 months)
Overall Survival between different SABR regimens + atezolizumab(24 months)