Clinical Trials/NCT03307759

NCT03307759

Terminated

Phase 1

Sequencing of Stereotactic Ablative Body Radiotherapy in Combination With PD-1 Blockade Using Pembrolizumab in Metastatic Non-Small Cell Lung Carcinoma

Peter MacCallum Cancer Centre, Australia1 site in 1 country13 target enrollmentDecember 7, 2017

ConditionsNon-small Cell Lung Cancer

InterventionsPembrolizumab Radiotherapy (SABR)

DrugsPembrolizumab

Overview

Phase: Phase 1
Intervention: Pembrolizumab
Conditions: Non-small Cell Lung Cancer
Sponsor: Peter MacCallum Cancer Centre, Australia
Enrollment: 13
Locations: 1
Primary Endpoint: Adverse Events Measured Using CTCAE Version 4.03
Status: Terminated
Last Updated: 7 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This investigator driven Phase Ib study will examine the safety, efficacy and biological effects of two schedules of pembrolizumab, an antibody targeted against anti-programmed cell death 1 (PD-1), which will be given either before or after stereotactic ablative body radiotherapy (SABR) for metastatic NSCLC.

Registry

clinicaltrials.gov

Start Date

December 7, 2017

End Date

January 31, 2022

Last Updated

7 months ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Peter MacCallum Cancer Centre, Australia

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Have provided written informed consent for the trial.
•Be ≥ 18 years of age on day of signing informed consent.
•Have at least one lesion not planned for SABR that is measurable disease based on RECIST 1.
•Patients must have a histologically or cytologically confirmed metastatic non-small cell lung cancer.
•Patients with disease previously untreated with systemic therapy must have ≥ 50% PD-L1 staining and patients who have previously received systemic therapy must have ≥ 1% PD-L1 staining on immunohistochemistry
•Patients must have at least 1-3 lesions suitable for treatment with stereotactic radiotherapy.
•Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumour lesion where feasible. Newly-obtained is defined as a specimen obtained up to 12 weeks 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 study principal investigators.
•Have a performance status of 0-1 on the ECOG Performance Scale (see Appendix 1).
•Demonstrate adequate organ function as defined in table 3 below, all screening labs should be performed within 10 days of randomisation.
•Table 3 Adequate Organ Function Laboratory Values

Exclusion Criteria

•Has had previous high dose radiotherapy (biological equivalent of \>30Gy in 10#) to an area to be treated which includes vertebral bodies (see below).
•Note: Previous high dose radiotherapy is defined as a biological equivalent dose to above that of 30 Gy in 10 fractions using an alpha/beta ratio (50) of
•Where a patient has received radiotherapy to an equivalent or lower dose than defined above, stereotactic radiotherapy of the area may be considered. In doing so, assessment of the volume and total dose received by any overlap region must be made, and documented by generating a cumulative plan incorporating both the previous and current treatment fields. It is the treating radiation oncologist's responsibility to review both the current plan and the cumulative plan inclusive of previous radiotherapy.
•Has had previous thoracic radiotherapy of \> 36Gy within the 6 months prior to randomisation.
•Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Patients with small asymptomatic or previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of enlarging brain metastases, and are not using steroids for intracranial neurological symptoms at least 7 days prior to trial randomisation. This exception does not include leptomeningeal disease which is excluded regardless of clinical stability.
•Has evidence of Spinal Cord Compression.
•Has a Spinal Instability Neoplastic Score ≥ 7 unless lesion reviewed by a neurosurgical service and considered stable (see Appendix 2).
•Requires surgical fixation of bone lesion for stability. All surgical fixation and instrumentation must be completed before randomisation on study.
•Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of randomisation.
•Has a diagnosis of immunodeficiency.

Arms & Interventions

SABR plus pembrolizumab

SABR followed by pembrolizumab

Intervention: Pembrolizumab

SABR plus pembrolizumab

SABR followed by pembrolizumab

Intervention: Radiotherapy (SABR)

Pembrolizumab plus SABR

Pembrolizumab followed by SABR after cycle 1

Intervention: Pembrolizumab

Pembrolizumab plus SABR

Pembrolizumab followed by SABR after cycle 1

Intervention: Radiotherapy (SABR)

Outcomes

Primary Outcomes

Adverse Events Measured Using CTCAE Version 4.03

Time Frame: Up to 24 months after commencement of treatment

Number of participants with grade 3 treatment related adverse events as determined using CTCAE version 4.03 criteria. Grade 3 treatment-related events are high grade toxicities.

Secondary Outcomes

Number of Participants With Overall Response (CR + PR) Assessed Using RECIST 1.1(Assessed up to 24 months)
Number of Participants With Overall Response (irCR + irPR) Assessed Using irRECIST(Assessed up to 24 months)
Number of Participants With Overall Response (CMR + PMC) Assessed Using PERCIST1.0(Assessed up to 24 months)
Number of Participants With Overall Response (CMRv + PMRv) Assessed Using Peter Mac Metabolic Response Criteria(Assessed up to 24 months)
Percentage of Participants With Overall Survival(24 months)
Percentage of Participants With Progression Free Survival (PFS)(12 months)