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Anti-PD(L)1 and SBRT in the Treatment of Advanced, Platinum-Refractory Urothelial Carcinoma

Primary Purpose

Urothelial Carcinoma

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Pembrolizumab
SBRT
Sponsored by
University of Michigan Rogel Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Urothelial Carcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Subjects must have a histologic diagnosis of urothelial carcinoma
  • Subjects must have radiologic evidence of metastatic disease with measurable disease by RECIST 1.1 criteria other than the target lesion(s) for SBRT
  • Subjects must have at least 1 metastatic lesion previously not radiated that is amenable to SBRT per treating radiation oncologist.
  • Subjects must have had progression of disease within 12 months of platinum-containing chemotherapy (chemotherapy could have been given in the neoadjuvant, adjuvant or metastatic setting) for urothelial cancer
  • ECOG performance status of 0 to 2 (Eastern Cooperative Oncology Group Performance Status: an attempt to quantify cancer patients' general well-being and activities of daily life. The score ranges from 0 to 5 where 0 is asymptomatic and 5 is death.)
  • Absolute neutrophil count of ≥ 1000/mm3, platelet count ≥ 100,000/mm3, hemoglobin ≥ 8.0 g/dl; total bilirubin/ALT/AST < 2.5 x upper limit of normal (patients with known gilbert disease who have serum bilirubin ≤3x ULN may be enrolled); serum creatinine <3.0mg/dl or if elevated, a calculated estimated glomerular filtration rate (eGFR) of ≥30 mL/min/1.73 m2
  • Subjects must have recovered to baseline or ≤ grade 1 CTCAE v 4.03 from toxicities related to any prior treatments unless AE(s) are clinically non-significant and/or stable on supportive therapy
  • Subjects must be ≥ 2 weeks from most recent systemic therapy or most recent radiation therapy
  • Women of childbearing potential must have a negative serum or urine pregnancy test within 28 days prior to registration.
  • Age ≥ 18 years

Exclusion Criteria:

  • Prior treatment with anti-PD-1/PD-L1 and anti-CTLA-4 is NOT allowed. Prior intravesical BCG (Bacillus Calmette-Guerin) therapy is allowed
  • Treatment with any investigational agent or on an interventional clinical trial within 30 days prior to registration.
  • No prior or concurrent malignancy is allowed except for: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, localized or locally advanced prostate cancer definitively treated without recurrence or with biochemical recurrence only, or any other cancer fully treated or from which the subject has been disease-free for at least 2 years.
  • Autoimmune diseases such as rheumatoid arthritis are NOT allowed. Vitiligo, mild psoriasis (topical therapy only) or hypothyroidism are allowed
  • Need for systemic corticosteroids >10mg prednisone daily or equivalent alternative steroid
  • Any history of organ allografts
  • Any history of HIV or hepatitis B infection
  • Known brain metastases

Sites / Locations

  • University of Michigan Comprehensive Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Pembrolizumab + SBRT

Arm Description

Outcomes

Primary Outcome Measures

The Percentage of Subjects Who Receive 4 Doses of Pembrolizumab and at Least One Session of Treatment of SBRT
Feasibility will be determined by the percentage of subjects who receive 4 doses of pembrolizumab and at least one session of treatment of SBRT (Stereotactic Body Radiation Therapy) within 15 weeks from the first dose of pembrolizumab.

Secondary Outcome Measures

The Number of Grades 3-5 Drug Related Adverse Events (AEs)
The number of grades 3-5 drug related adverse events (AEs) will be recorded. AEs will be graded using the CTCAE v4.03
The Percentage of Patients That Respond to Treatment
The percentage of patients that achieve either a complete response (CR) or partial response (PR). Response will be reported separately using RECIST and irRECIST criteria. CR (RECIST): Disappearance of all target lesions, determined by two separate observations conducted not less than 4 weeks apart. There can be no appearance of new lesions CR (irRECIST): Disappearance of all lesions in two consecutive observations not less than 4 wk apart PR (RECIST): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. There can be no appearance of new lesions PR (irRECIST): ≥50% decrease in tumor burden compared with baseline in two observations at least 4 wk apart
Progression Free Survival (PFS) Time
Progression-free survival (PFS) is defined as the duration of time from start of treatment to time of progressive disease (PD), or death, whichever occurs first, up to 24 months. PD (RECIST): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started, or the appearance of one or more new lesions PD (irRECIST): At least 25% increase in tumor burden compared with nadir (at any single time point) in two consecutive observations at least 4 wk apart

Full Information

First Posted
September 15, 2017
Last Updated
December 13, 2021
Sponsor
University of Michigan Rogel Cancer Center
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1. Study Identification

Unique Protocol Identification Number
NCT03287050
Brief Title
Anti-PD(L)1 and SBRT in the Treatment of Advanced, Platinum-Refractory Urothelial Carcinoma
Official Title
FAST: Feasibility Trial of Anti-PD(L)1 and SBRT in the Treatment of Advanced, Platinum-Refractory Urothelial Carcinoma
Study Type
Interventional

2. Study Status

Record Verification Date
December 2021
Overall Recruitment Status
Terminated
Why Stopped
due to changing therapeutic landscape in metastatic bladder cancer and lack of radiation/immunotherapy systemic synergy in other malignancies
Study Start Date
January 24, 2018 (Actual)
Primary Completion Date
March 13, 2019 (Actual)
Study Completion Date
November 10, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Michigan Rogel Cancer Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is a feasibility trial of anti-PDL1/PD1 (pembrolizumab) and stereotactic body radiation therapy (SBRT) in patients with advanced, platinum-refractory urothelial carcinoma.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Urothelial Carcinoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
6 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Pembrolizumab + SBRT
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Pembrolizumab
Intervention Description
200 mg IV q 21 days
Intervention Type
Radiation
Intervention Name(s)
SBRT
Intervention Description
Stereotactic body radiation therapy (SBRT) that will commence not later than the initiation of the second cycle of pembrolizumab. SBRT dose and fractionation will be at the discretion of the treating radiation oncologist, and will be selected to respect the normal tissue tolerance of adjacent organs at risk.
Primary Outcome Measure Information:
Title
The Percentage of Subjects Who Receive 4 Doses of Pembrolizumab and at Least One Session of Treatment of SBRT
Description
Feasibility will be determined by the percentage of subjects who receive 4 doses of pembrolizumab and at least one session of treatment of SBRT (Stereotactic Body Radiation Therapy) within 15 weeks from the first dose of pembrolizumab.
Time Frame
15 weeks
Secondary Outcome Measure Information:
Title
The Number of Grades 3-5 Drug Related Adverse Events (AEs)
Description
The number of grades 3-5 drug related adverse events (AEs) will be recorded. AEs will be graded using the CTCAE v4.03
Time Frame
30 days post last dose
Title
The Percentage of Patients That Respond to Treatment
Description
The percentage of patients that achieve either a complete response (CR) or partial response (PR). Response will be reported separately using RECIST and irRECIST criteria. CR (RECIST): Disappearance of all target lesions, determined by two separate observations conducted not less than 4 weeks apart. There can be no appearance of new lesions CR (irRECIST): Disappearance of all lesions in two consecutive observations not less than 4 wk apart PR (RECIST): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. There can be no appearance of new lesions PR (irRECIST): ≥50% decrease in tumor burden compared with baseline in two observations at least 4 wk apart
Time Frame
51 weeks (up to 17, 3 week doses)
Title
Progression Free Survival (PFS) Time
Description
Progression-free survival (PFS) is defined as the duration of time from start of treatment to time of progressive disease (PD), or death, whichever occurs first, up to 24 months. PD (RECIST): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started, or the appearance of one or more new lesions PD (irRECIST): At least 25% increase in tumor burden compared with nadir (at any single time point) in two consecutive observations at least 4 wk apart
Time Frame
24 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Subjects must have a histologic diagnosis of urothelial carcinoma Subjects must have radiologic evidence of metastatic disease with measurable disease by RECIST 1.1 criteria other than the target lesion(s) for SBRT Subjects must have at least 1 metastatic lesion previously not radiated that is amenable to SBRT per treating radiation oncologist. Subjects must have had progression of disease within 12 months of platinum-containing chemotherapy (chemotherapy could have been given in the neoadjuvant, adjuvant or metastatic setting) for urothelial cancer ECOG performance status of 0 to 2 (Eastern Cooperative Oncology Group Performance Status: an attempt to quantify cancer patients' general well-being and activities of daily life. The score ranges from 0 to 5 where 0 is asymptomatic and 5 is death.) Absolute neutrophil count of ≥ 1000/mm3, platelet count ≥ 100,000/mm3, hemoglobin ≥ 8.0 g/dl; total bilirubin/ALT/AST < 2.5 x upper limit of normal (patients with known gilbert disease who have serum bilirubin ≤3x ULN may be enrolled); serum creatinine <3.0mg/dl or if elevated, a calculated estimated glomerular filtration rate (eGFR) of ≥30 mL/min/1.73 m2 Subjects must have recovered to baseline or ≤ grade 1 CTCAE v 4.03 from toxicities related to any prior treatments unless AE(s) are clinically non-significant and/or stable on supportive therapy Subjects must be ≥ 2 weeks from most recent systemic therapy or most recent radiation therapy Women of childbearing potential must have a negative serum or urine pregnancy test within 28 days prior to registration. Age ≥ 18 years Exclusion Criteria: Prior treatment with anti-PD-1/PD-L1 and anti-CTLA-4 is NOT allowed. Prior intravesical BCG (Bacillus Calmette-Guerin) therapy is allowed Treatment with any investigational agent or on an interventional clinical trial within 30 days prior to registration. No prior or concurrent malignancy is allowed except for: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, localized or locally advanced prostate cancer definitively treated without recurrence or with biochemical recurrence only, or any other cancer fully treated or from which the subject has been disease-free for at least 2 years. Autoimmune diseases such as rheumatoid arthritis are NOT allowed. Vitiligo, mild psoriasis (topical therapy only) or hypothyroidism are allowed Need for systemic corticosteroids >10mg prednisone daily or equivalent alternative steroid Any history of organ allografts Any history of HIV or hepatitis B infection Known brain metastases
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Zachery Reichert, MD, PhD
Organizational Affiliation
University of Michigan Rogel Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Michigan Comprehensive Cancer Center
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Anti-PD(L)1 and SBRT in the Treatment of Advanced, Platinum-Refractory Urothelial Carcinoma

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