Stereotactic Radiotherapy and Anti-PD1 Antibody (Pembrolizumab) for Oligometastatic Renal Tumours

Peter MacCallum Cancer Centre, Australia2 sites in 1 country30 target enrollmentOctober 20, 2016

ConditionsRenal Cell Carcinoma

InterventionsStereotactic Ablative Body Radiosurgery (SABR)Pembrolizumab

DrugsPembrolizumab

Overview

Phase: Phase 1
Intervention: Stereotactic Ablative Body Radiosurgery (SABR)
Conditions: Renal Cell Carcinoma
Sponsor: Peter MacCallum Cancer Centre, Australia
Enrollment: 30
Locations: 2
Primary Endpoint: Toxicities Measured Using CTCAE Version 4.03
Status: Completed
Last Updated: 2 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This investigator driven study will examine the safety, efficacy and biological effects of combining pembrolizumab (MK-3475) an antibody targeted against anti-programmed cell death 1 (PD-1), with stereotactic ablative body radiotherapy (SABR) for oligometastatic renal cell carcinoma (RCC). The investigators hypothesise that the safety profile of this combination will be clinically acceptable.

Detailed Description

Dual institutional, single arm, unblinded, phase I/II study.

Registry

clinicaltrials.gov

Start Date

October 20, 2016

End Date

May 22, 2020

Last Updated

2 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Peter MacCallum Cancer Centre, Australia

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Has provided written informed consent for the trial.
•Be at least 18 years of age on day of signing informed consent.
•Have oligometastases (1-5 metastases), and measurable disease based on RECIST 1.
•Participants must have a histologically or cytologically confirmed metastatic renal cell carcinoma. Oligometastatic lesions do not need to be biopsied but they must be clinically consistent to represent metastatic disease.
•Patient can either be treatment naïve or have previously received up to 2 lines of systemic treatment (eg. Pazopanib or Sunitinib). The total number of metastases throughout the pre-trial period should not number more than
•Must have had surgical consideration for metastasectomy and thought appropriate for SABR due to medical inoperability, technical factors or patient declining surgery.
•Must have at least one metastasis for which SABR is technically deliverable.
•Be willing to provide archival tissue from a previously biopsied or excised primary or metastatic RCC lesion (if available). If safe to do so, a request for newly obtained specimen (obtained up to 4 weeks prior to initiation of treatment) will be made, however participation for this biopsy is entirely optional.
•Have a performance status of 0-2 on the ECOG Performance Scale
•Demonstrate adequate organ function as defined below all screening labs should be performed within 10 days of registration.

Exclusion Criteria

•Based on clinician assessment of disease volume and rate of progression of patient's tumor deposits, the patient requires immediate TKI therapy.
•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 \[82\] 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 evidence of untreated or active intracranial metastases. Patients who have had fully resected brain metastasis or those controlled by stereotactic radiotherapy are eligible as long as they are not requiring corticosteroids for symptomatic control.
•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 3).
•Requires surgical fixation of bone lesion for stability. This must be performed before enrollment into the trial.
•Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days of registration.
•Has a known history of active TB (Bacillus Tuberculosis).

Arms & Interventions

SABR + Pembrolizumab

SABR treatment (18Gy-20Gy/1#) followed by 200mg pembrolizumab IV once every 3 weeks for a total of 8 cycles

Intervention: Stereotactic Ablative Body Radiosurgery (SABR)

SABR + Pembrolizumab

SABR treatment (18Gy-20Gy/1#) followed by 200mg pembrolizumab IV once every 3 weeks for a total of 8 cycles

Intervention: Pembrolizumab

Outcomes

Primary Outcomes

Toxicities Measured Using CTCAE Version 4.03

Time Frame: Up to 24 months after SABR treatment

Number of Participants with Grade 3 Treatment Related Adverse Events as determined using CTCAE version 4.03 criteria. This standard criteria can be found through National Cancer Institute (https://ctep.cancer.gov/protocoldevelopment/electronic_applications/ctc.htm). Grade 3 treatment-related events are high grade toxicities.

Secondary Outcomes

Distant Progression Free Survival (DPFS)(From start of treatment until the date of first distant progression or until the date of death from any cause, whichever occurs first, assessed at 2 years)
Pain Assessed Using the Numerical Pain Rating Scale(From commencement of treatment up to 2 years.)
Freedom From Local Progression (FFLP)(From start of treatment until the date of first local progression or until the date of death from any cause, whichever occurs first, assessed up to 2 years)
Overall Survival(From start of treatment until the date of death from any cause assessed up to 2 years)
Overall Response Assessed Using RECIST 1.1(24 months)