Clinical trial NCT03287050: 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
Overall status: TERMINATED
Phase: PHASE2
Conditions: Urothelial Carcinoma
Lead sponsor: University of Michigan Rogel Cancer Center
Sponsor class: OTHER
First posted: 2017-09-19
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: The Percentage of Subjects Who Receive 4 Doses of Pembrolizumab and at Least One Session of Treatment of SBRT
timeFrame: 15 weeks
Secondary outcomes:
measure: The Number of Grades 3-5 Drug Related Adverse Events (AEs)
timeFrame: 30 days post last dose
measure: The Percentage of Patients That Respond to Treatment
timeFrame: 51 weeks (up to 17, 3 week doses)
measure: Progression Free Survival (PFS) Time
timeFrame: 24 months
Other outcomes:
Locations:
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
Study officials:
affiliation: University of Michigan Rogel Cancer Center
name: Zachery Reichert, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: