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

• ClinicalTrials.gov Identifier: NCT03287050
• Recruitment Status: Terminated
• First Posted: September 19, 2017
• Results First Posted: December 15, 2021
• Last Update Posted: December 15, 2021
• Sponsor: University of Michigan Rogel Cancer Center
• Information provided by (Responsible Party): University of Michigan Rogel Cancer Center

Tracking Information

• First Submitted Date: September 15, 2017
• First Posted Date: September 19, 2017
• Results First Submitted Date: September 21, 2021
• Results First Posted Date: December 15, 2021
• Last Update Posted Date: December 15, 2021
• Actual Study Start Date: January 24, 2018
• Actual Primary Completion Date: March 13, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 25, 2021)

The Percentage of Subjects Who Receive 4 Doses of Pembrolizumab and at Least One Session of Treatment of SBRT [ Time Frame: 15 weeks ]

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.

Original Primary Outcome Measures (submitted: September 15, 2017)

The percentage of subjects who receive 4 doses of pembrolizumab and at least one session of treatment of SBRT [ Time Frame: 15 weeks ]

Feasibility will be determined by the proportion 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.

Current Secondary Outcome Measures (submitted: December 10, 2021)

• The Number of Grades 3-5 Drug Related Adverse Events (AEs) [ Time Frame: 30 days post last dose ]
  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 [ Time Frame: 51 weeks (up to 17, 3 week doses) ]
  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 [ Time Frame: 24 months ]
  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

Original Secondary Outcome Measures (submitted: September 15, 2017)

• The number of grades 3-5 drug related adverse events (AEs) [ Time Frame: 30 days post last dose ]
  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 [ Time Frame: 51 weeks (up to 17, 3 week doses) ]
  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 [ Time Frame: 24 months ]
  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. PFS will be reported separately using RECIST and irRECIST. 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

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Urothelial Carcinoma

Intervention

• Drug: Pembrolizumab
  200 mg IV q 21 days
• Radiation: SBRT
  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.

Study Arms

Experimental: Pembrolizumab + SBRT

Interventions:

• Drug: Pembrolizumab
• Radiation: SBRT

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: December 4, 2019): 6
• Original Estimated Enrollment (submitted: September 15, 2017): 20
• Actual Study Completion Date: November 10, 2020
• Actual Primary Completion Date: March 13, 2019 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03287050
• Other Study ID Numbers: UMCC 2017.069; HUM00135161 ( Other Identifier: University of Michigan )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• 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

• IPD Sharing Statement: Not Provided
• Current Responsible Party: University of Michigan Rogel Cancer Center
• Original Responsible Party: Same as current
• Current Study Sponsor: University of Michigan Rogel Cancer Center
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Zachery Reichert, MD, PhD; University of Michigan Rogel Cancer Center

• PRS Account: University of Michigan Rogel Cancer Center
• Verification Date: December 2021