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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03287050
Recruitment Status : Terminated (due to changing therapeutic landscape in metastatic bladder cancer and lack of radiation/immunotherapy systemic synergy in other malignancies)
First Posted : September 19, 2017
Results First Posted : December 15, 2021
Last Update Posted : December 15, 2021
Information provided by (Responsible Party):
University of Michigan Rogel Cancer Center

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.

Condition or disease Intervention/treatment Phase
Urothelial Carcinoma Drug: Pembrolizumab Radiation: SBRT Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 6 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: FAST: Feasibility Trial of Anti-PD(L)1 and SBRT in the Treatment of Advanced, Platinum-Refractory Urothelial Carcinoma
Actual Study Start Date : January 24, 2018
Actual Primary Completion Date : March 13, 2019
Actual Study Completion Date : November 10, 2020

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Pembrolizumab + SBRT 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.

Primary Outcome Measures :
  1. 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.

Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03287050

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United States, Michigan
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, United States, 48109
Sponsors and Collaborators
University of Michigan Rogel Cancer Center
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Principal Investigator: Zachery Reichert, MD, PhD University of Michigan Rogel Cancer Center
  Study Documents (Full-Text)

Documents provided by University of Michigan Rogel Cancer Center:
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Responsible Party: University of Michigan Rogel Cancer Center
ClinicalTrials.gov Identifier: NCT03287050    
Other Study ID Numbers: UMCC 2017.069
HUM00135161 ( Other Identifier: University of Michigan )
First Posted: September 19, 2017    Key Record Dates
Results First Posted: December 15, 2021
Last Update Posted: December 15, 2021
Last Verified: December 2021

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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
Additional relevant MeSH terms:
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Carcinoma, Transitional Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action