Stereotactic Radiation and Immunotherapy in Patients With Advanced Triple Negative Breast Cancer

NCT03464942 | Completed Phase 2 DMC

• 1 other identifier: 17/013
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

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.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival

  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).

  24 months

Secondary Outcomes (7)

• Best Objective Response (BOR) between different SABR regimens + atezolizumab

  24 months

• Incidence of treatment emergent adverse events (safety and tolerability)

  24 months

• Progression Free Survival Comparison 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

Study Arms (2)

Single Dose

ACTIVE COMPARATOR

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.

Radiation: SABR; Drug: Atezolizumab

Fractionated Dose

ACTIVE COMPARATOR

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.

Radiation: SABR; Drug: Atezolizumab

Interventions

SABR RADIATION

Single Dose Group: this group will receive 20 Gy of radiation in a single dose within 10 days of randomisation Fractionated Dose: Participants in this dose will receive a total of 24Gy of radiation given as 3 separate fractions of 8 Gy each.

Fractionated Dose; Single Dose

Atezolizumab DRUG

All participants will commence atezolizumab (within 5 days of last SABR dose) 1200 mg every 3 weeks for 24 months

Fractionated Dose; Single Dose

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Female participants of childbearing potential must have a negative urine or serum pregnancy within 7 days of trial randomisation.
• Female participants of childbearing potential must be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the trial through to 5 months after the last dose of atezolizumab.
• Male participants must agree to use an adequate method of contraception starting with the first SABR treatment, through to 120 days after the last dose of atezolizumab.
• Adequate Organ Function as defined in the table below:
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L,

You may not qualify if:

• 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.
• Has a known additional malignancy that is progressing or requires active treatment.
• Has uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently).
• Note: Participants with indwelling catheters (e.g., PleurX) are allowed.
• Has uncontrolled hypercalcemia (\> 1.5mmol/L ionized calcium or serum calcium \>2.99mmol/L or corrected serum calcium \>ULN) or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab. Note: Participants who are receiving bisphosphonate therapy or denosumab specifically to prevent skeletal events and who do not have a history of clinically significant hypercalcemia are eligible.
• Has a significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within 3 months prior to Cycle 1, Day 1, unstable arrhythmias or unstable angina. Note: Participants with a known left ventricular ejection fraction (LVEF) \< 40% will be excluded.

Sponsors & Collaborators

• Peter MacCallum Cancer Centre, Australia: lead
• Trans Tasman Radiation Oncology Group: collaborator

Study Sites (1)

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3000, Australia

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

atezolizumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Sherene Loi, Prof

  Peter MacCallum Cancer Centre, Australia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants with triple negative breast cancer will be randomised to receive either SABR 20Gy in one fraction or 24 Gy in 3 fractions , they will then go onto receive atezolizumab for up to 24 months

Study Record Dates

• First Submitted: February 21, 2018
• First Posted: March 14, 2018
• Study Start: August 1, 2018
• Primary Completion: June 22, 2023
• Study Completion: June 22, 2023
• Last Updated: July 19, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)