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.
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
Interventions
Drug | Synonyms | Arms |
---|
Pembrolizumab | | Pembrolizumab + 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
Name | Type | Description | Interventions |
---|
Pembrolizumab + SBRT | Experimental | | |
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: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Completed |
Lead Sponsor: | University of Michigan Rogel Cancer Center |
Last Updated
December 30, 2020