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

NCT02855203 | Completed Phase 1 Results DMC

• 1 other identifier: 15/143
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

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.

Conditions

Renal Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• Toxicities Measured Using CTCAE Version 4.03

  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.

  Up to 24 months after SABR treatment

Secondary Outcomes (5)

• Overall Survival

  From start of treatment until the date of death from any cause assessed 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

• 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

• Overall Response Assessed Using RECIST 1.1

  24 months

• Pain Assessed Using the Numerical Pain Rating Scale

  From commencement of treatment up to 2 years.

Study Arms (1)

SABR + Pembrolizumab

EXPERIMENTAL

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

Radiation: Stereotactic Ablative Body Radiosurgery (SABR); Drug: Pembrolizumab

Interventions

Stereotactic Ablative Body Radiosurgery (SABR) RADIATION

18-20Gy in 1 fraction

SABR + Pembrolizumab

Pembrolizumab DRUG

Pembrolizumab at a dose of 200mg IV, 3-weekly will be delivered for a duration of 6 months, commencing 5 days (+/- 3 days) from the last dose of SABR.

SABR + Pembrolizumab

Eligibility Criteria

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

You may qualify if:

• 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 1.1.
• 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 5.
• 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.
• Absolute neutrophil count (ANC) - ≥1.5 X 10\^9/L
• Platelets - ≥100 X 10\^9/L
• Hemoglobin - ≥90 g/L or ≥5.6 mmol/L without transfusion or EPO dependency (within 7 days of assessment)
• Serum creatinine OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) - ≤1.5 X upper limit of normal (ULN) OR ≥60 mL/min for participant with creatinine levels \> 1.5 X institutional ULN
• Serum total bilirubin - ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for participants with total bilirubin levels \> 1.5 ULN

You may not qualify if:

• 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 3. 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).
• Hypersensitivity to pembrolizumab or any of its excipients.
• Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks of registration or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
• Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks of registration or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
• Note: Participants with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
• Note: If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.

Sponsors & Collaborators

• Peter MacCallum Cancer Centre, Australia: lead

Study Sites (2)

Princess Alexandra Hospital

Woolloongabba, Queensland, 4102, Australia

Location

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3000, Australia

Location

Related Publications (2)

• Siva S, Bressel M, Wood ST, Shaw MG, Loi S, Sandhu SK, Tran B, A Azad A, Lewin JH, Cuff KE, Liu HY, Moon D, Goad J, Wong LM, LimJoon M, Mooi J, Chander S, Murphy DG, Lawrentschuk N, Pryor D. Stereotactic Radiotherapy and Short-course Pembrolizumab for Oligometastatic Renal Cell Carcinoma-The RAPPORT Trial. Eur Urol. 2022 Apr;81(4):364-372. doi: 10.1016/j.eururo.2021.12.006. Epub 2021 Dec 23.

  PMID: 34953600 DERIVED

• Pryor D, Bressel M, Lawrentschuk N, Tran B, Mooi J, Lewin J, Azad A, Colyer D, Neha N, Shaw M, Chander S, Neeson P, Moon D, Cuff K, Wood S, Murphy DG, Sandhu S, Loi S, Siva S. A phase I/II study of stereotactic radiotherapy and pembrolizumab for oligometastatic renal tumours (RAPPORT): Clinical trial protocol. Contemp Clin Trials Commun. 2021 Jan 6;21:100703. doi: 10.1016/j.conctc.2021.100703. eCollection 2021 Mar.

  PMID: 33490707 DERIVED

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Results Point of Contact

• Title: Office of Cancer Research
• Organization: Peter MacCallum Cancer Centre

OCR@petermac.org

+61 3 85597364

Study Officials

• Shankar Siva, Prof

  Peter MacCallum Cancer Centre, Australia

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 28, 2016
• First Posted: August 4, 2016
• Study Start: October 20, 2016
• Primary Completion: May 22, 2020
• Study Completion: May 22, 2020
• Last Updated: August 3, 2023
• Results First Posted: August 3, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

AU (2)