Phase I Trial of Stereotactic Body Radiotherapy With Concurrent Pembrolizumab in Metastatic Urothelial Cancer

University Hospital, Ghent1 site in 1 country18 target enrollmentNovember 14, 2016

ConditionsMetastatic Urothelial Cancer

Interventionspembrolizumab

Drugspembrolizumab

Overview

Phase: Phase 1
Intervention: pembrolizumab
Conditions: Metastatic Urothelial Cancer
Sponsor: University Hospital, Ghent
Enrollment: 18
Locations: 1
Primary Endpoint: Selection of the sequence arm with a DLT < 20% based on the incidence of treatment-related adverse events
Status: Completed
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The goal of the proposed research project is to assess the safety (dose limiting toxicity, DLT) of the combination of pembrolizumab and high-dose stereotactic body radiotherapy (SBRT) in patients with metastatic urothelial cancer. Both the SBRT dose and pembrolizumab dose will be fixed, but the timing of the combination will be varied. Secondary objectives include response rates, local control, progression-free survival (PFS) and overall survival (OS). Exploratory endpoints include immunologic responses and response rates in PD-L1- TIL- tumors. The combination sequence with the most promising response rates and the best safety profile will be selected to continue in a Phase II trial.

Registry

clinicaltrials.gov

Start Date

November 14, 2016

End Date

February 18, 2019

Last Updated

last year

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

University Hospital, Ghent

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Be willing and able to provide written informed consent/assent for the trial.
•Be ≥ 18 years of age on day of signing informed consent.
•Have measurable disease based on RECIST 1.
•Have had any prior treatment more than 2 weeks prior to study day 1, treatment naïve patients are allowed
•Histologically confirmed diagnosis of urothelial carcinoma
•Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion. Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on Day
•Subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen only upon agreement from the Sponsor.
•Have a performance status of 0 or 1 on the ECOG Performance Scale.
•Demonstrate adequate organ function, all screening labs should be performed within 10 days before treatment initiation.
•(Adequate organ function: Absolute neutrophil count (ANC) ≥1,500 /mcL, Platelets ≥100,000 / mcL, Hemoglobin ≥9 g/dL 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 subject with creatinine levels \> 1.5 X institutional ULN, Serum total bilirubin ≤ 1.5 X ULN OR direct bilirubin ≤ ULN for subjects with total bilirubin levels \> 1.5 ULN, AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN OR ≤ 5 X ULN for subjects with liver metastases, Albumin \>2.5 mg/dL, International Normalized Ratio (INR) or Prothrombin Time (PT) Activated Partial Thromboplastin Time (aPTT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy (as long as PT or PTT is within therapeutic range of intended use of anticoagulants ≤1.5 X ULN unless subject is receiving anticoagulant therapy, as long as PT or PTT is within therapeutic range of intended use of anticoagulants a Creatinine clearance should be calculated per institutional standard)

Exclusion Criteria

•The subject must be excluded from participating in the trial if the subject:
•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 the first dose of treatment.
•Has had radiotherapy interfering with SBRT.
•Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
•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 prior to study Day 1 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 prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
•Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
•Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.

Arms & Interventions

Sequential

Stereotactic body radiotherapy prior to pembrolizumab treatment

Intervention: pembrolizumab

Concurrent

Stereotactic body radiotherapy concurrent with pembrolizumab treatment

Intervention: pembrolizumab

Outcomes

Primary Outcomes

Selection of the sequence arm with a DLT < 20% based on the incidence of treatment-related adverse events

Time Frame: 12 weeks post-radiotherapy

Toxicities will be considered as DLT if occurring between the start of SBRT and 12 weeks after completion of SBRT. DLT will be assessed using the Common Terminology Criteria for Adverse Events.