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

NCT03287050 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: UMCC 2017.069HUM00135161
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

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.

Conditions

Urothelial Carcinoma

Outcome Measures

Primary Outcomes (1)

• The Percentage of Subjects Who Receive 4 Doses of Pembrolizumab and at Least One Session of Treatment of SBRT

  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.

  15 weeks

Secondary Outcomes (3)

• The Number of Grades 3-5 Drug Related Adverse Events (AEs)

  30 days post last dose

• The Percentage of Patients That Respond to Treatment

  51 weeks (up to 17, 3 week doses)

• Progression Free Survival (PFS) Time

  24 months

Study Arms (1)

Pembrolizumab + SBRT

EXPERIMENTAL

Drug: Pembrolizumab; Radiation: SBRT

Interventions

Pembrolizumab DRUG

200 mg IV q 21 days

Pembrolizumab + SBRT

SBRT RADIATION

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.

Pembrolizumab + SBRT

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Michigan Rogel Cancer Center: lead

Study Sites (1)

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

MeSH Terms

Conditions

Carcinoma, Transitional Cell

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Limitations and Caveats

This study was closed early (at 6 patients) due to changing therapeutic landscape in metastatic bladder cancer and lack of radiation/immunotherapy systemic synergy in other malignancies.

Results Point of Contact

• Title: Zachery Reichert
• Organization: University of Michigan

zreiche@med.umich.edu

764-3066

Study Officials

• Zachery Reichert, MD, PhD

  University of Michigan Rogel Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 15, 2017
• First Posted: September 19, 2017
• Study Start: January 24, 2018
• Primary Completion: March 13, 2019
• Study Completion: November 10, 2020
• Last Updated: December 15, 2021
• Results First Posted: December 15, 2021

Record last verified: 2021-12

Locations

US (1)