Stereotactic Ablative Radiation for Oligo-Progression of Urothelial Cancer (SAbR)

A Phase II Trial of Stereotactic Ablative Radiation (SAbR) for Urothelial Cancer Patients With Progression While on Anti-PD-1/PD-L1 Immunotherapy

To evaluate the benefit of SAbR for oligo-progressive metastatic urothelial cancer.

Study Overview

• Status: Terminated
• Conditions: Urothelial Cancer
• Intervention / Treatment: Radiation: Stereotactic Ablative Radiation

Detailed Description

Oligo-progressive urothelial cancer with limited disease burden and progression on an anti-PD-1/L1 immune checkpoint inhibitor.

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75390
      • Aurelie Garant

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients must be at least 18-years-old
• ECOG performance status 0-2
• Patients must have pathology-proven metastatic urothelial carcinoma, with tissue sampling of at least the primary tumor. Tissue sampling of each presumed metastatic site is not necessary, provided that the patient already has a confirmed diagnosis of urothelial cancer.

• Patients must be on immune checkpoint inhibitor therapy with radiographic scans to verify oligo-progression of at least one and ≤ 6 sites of disease per RECIST 1.1.

  • Any of the currently FDA-approved PD-1/PD-L1 inhibitors are allowed. These include pembrolizumab, nivolumab, atezolizumab, avelumab, and durvalumab.
  • At least 1 metastatic lesion must show stable disease, partial response or complete response per RECIST 1.1.
• Patients must be able to understand and willing to sign written informed consent.
• Patients must have acceptable tolerability of ongoing therapy as decided by the treating medical oncologist.
• Patients must have a desire to continue ongoing therapy.
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy.

• A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:

  • Has not undergone a hysterectomy or bilateral oophorectomy, or has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
  • Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.

Exclusion Criteria:

• Inability to receive further immune checkpoint inhibitor therapy
• Anticipated survival of fewer than 12 weeks
• Daily steroid requirement of > 10 mg prednisone or prednisone-equivalent. Steroid replacement therapy for adrenal insufficiency is permitted.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements.
• Subjects must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SAbR 6 measurable lesions; PD-L1 assessment on biopsy of metastatic site (biopsy will be performed if no prior metastasis sample available)	Radiation: Stereotactic Ablative Radiation; A stereotactic relocalization system that relies upon stereoscopic radiographs, implanted fiducials, or near real-time CT based verification will be used.Investigators will have the discretion to choose from biologically equivalent dose levels using 1, 3 or 5 fractions. All active lesions need to be addressed by local therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival (PFS) at 6 months	Progression free survival (PFS) at 6 months in the patients for whom SAbR is added to the ICI after progression on ICI. PFS will be defined as the combination of progressive disease from SAbR start date and death from any cause.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The disease control rate	The disease control rate in patients for whom SAbR is added to ICI after progression on ICI. DCR will be assessed per RECIST 1.1 criteria and defined as the combination of: Complete Response (CR), Partial Response (PR), or Stable Disease (SD).	6 months
The time to next-line systemic therapy	The time to initiation of next-line systemic therapy following the addition of SAbR to ICI after progression on ICI.	6 months
Overall survival of patients	The overall survival of patients since progression on ICI or at the study registration. Overall survival (OS) will be defined using the interval between enrollment and death from any cause.	6 months

Collaborators and Investigators

• Sponsor: University of Texas Southwestern Medical Center
• Investigators: Principal Investigator: Aurelie Garant, University of Texas Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): January 16, 2020
• Primary Completion (Actual): December 17, 2020
• Study Completion (Actual): June 10, 2021

Study Registration Dates

• First Submitted: October 16, 2019
• First Submitted That Met QC Criteria: October 16, 2019
• First Posted (Actual): October 18, 2019

Study Record Updates

• Last Update Posted (Actual): June 16, 2021
• Last Update Submitted That Met QC Criteria: June 10, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Other Study ID Numbers: 2019-1506

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No