Clinical Trials /

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

NCT03287050

Description:

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

Related Conditions:
  • Urothelial Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Early Phase 1

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: UMCC 2017.069
  • SECONDARY ID: HUM00135161
  • NCT ID: NCT03287050

Conditions

  • Urothelial Carcinoma

Interventions

DrugSynonymsArms
PembrolizumabPembrolizumab + SBRT

Purpose

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

Trial Arms

NameTypeDescriptionInterventions
Pembrolizumab + SBRTExperimental
  • Pembrolizumab

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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:The percentage of subjects who receive 4 doses of pembrolizumab and at least one session of treatment of SBRT
Time Frame:15 weeks
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:The number of grades 3-5 drug related adverse events (AEs)
Time Frame:30 days post last dose
Safety Issue:
Description:The number of grades 3-5 drug related adverse events (AEs) will be recorded. AEs will be graded using the CTCAE v4.03
Measure:The percentage of patients that respond to treatment
Time Frame:51 weeks (up to 17, 3 week doses)
Safety Issue:
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
Measure:Progression free survival (PFS) time
Time Frame:24 months
Safety Issue:
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. 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

Details

Phase:Early Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Michigan Rogel Cancer Center

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