Phase 2 Trial of Tremelimumab in Patients With Metastatic Urothelial Cancer Previously Treated With PD-1/PD-L1 Blockade

Matthew Galsky7 sites in 1 country26 target enrollmentNovember 12, 2018

ConditionsUrothelial Carcinoma

InterventionsTremelimumab

DrugsTremelimumab

Overview

Phase: Phase 2
Intervention: Tremelimumab
Conditions: Urothelial Carcinoma
Sponsor: Matthew Galsky
Enrollment: 26
Locations: 7
Primary Endpoint: Objective Response Rate
Status: Completed
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This is a phase II trial designed to estimate the activity of single agent tremelimumab in subjects with metastatic urothelial cancer with disease progression despite prior treatment with PD-1/PD-L1 blockade. The primary endpoint is objective response rate and the study will employ a Simon's 2-stage design.

Registry

clinicaltrials.gov

Start Date

November 12, 2018

End Date

June 7, 2023

Last Updated

last year

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Matthew Galsky

Responsible Party

Sponsor Investigator

Principal Investigator

Matthew Galsky

Sponsor-Investigator

Hoosier Cancer Research Network

Eligibility Criteria

Inclusion Criteria

•Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
•ECOG Performance Status of 0 or 1 within 14 days prior to registration.
•Histologically or cytologically documented urothelial cancer. Locally advanced (T4b, any N; or any T, N 2-3) or metastatic disease (M1, Stage IV) (also termed TCC or UCC of the urinary tract; including renal pelvis, ureters, urinary bladder, and urethra). Subjects with mixed histologies are eligible provided that the predominant component is urothelial cancer. Locally advanced bladder cancer must be inoperable on the basis of involvement of pelvic sidewall or adjacent viscera (clinical Stage T4b) or bulky nodal metastasis (N2-N3).
•Representative formalin-fixed paraffin-embedded (FFPE) tumor specimens in paraffin blocks (blocks preferred) or at least 15 unstained slides. If archival tissue is not available and the subject is undergoing a standard of care biopsy, tissue from the biopsy is required to be submitted for correlative analyses. Subjects without adequate baseline tumor tissue may be considered for enrollment on a case by case basis after discussion with the sponsor-investigator.
•Measurable disease according to RECIST 1.1 within 28 days prior to registration. At least 1 lesion, not previously irradiated, that can be accurately measured at baseline as ≥10 mm in the longest diameter (except lymph nodes, which must have short axis ≥15 mm) with computed tomography (CT) (preferred) or magnetic resonance imaging (MRI) scans, preferably with IV contrast, and that is suitable for accurate repeated measurements as per RECIST 1.1 guidelines; lesions in a previously irradiated field can be used as a measurable disease provided that there has been demonstrated progression in the lesion.
•A subject with prior brain metastasis may be considered if they have completed their treatment for brain metastasis at least 4 weeks prior to study registration, have been off of corticosteroids for ≥ 2 weeks, and are asymptomatic
•Subjects must have progressed despite prior treatment with anti-PD-1/PD-L1 antibody therapy. In addition, subjects must meet the following criteria:
•Subjects must not have progressed within 2 months of starting prior anti-PD-1/PD-L1 antibody therapy.
•Subjects must have received at least 1 line of prior systemic therapy
•Must not have experienced a toxicity that led to permanent discontinuation of prior immunotherapy.

Exclusion Criteria

•Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
•Known additional malignancy that is active and/or progressive requiring treatment. Patients with incidental histologic findings of prostate cancer (tumor/node/metastasis stage of T1a or T1b or prostate-specific antigen \<10) who have not received hormonal treatment may be included, pending a discussion with the sponsor-investigator
•Treatment with any investigational drug within 28 days prior to registration.
•Prior treatment with an anti-CTLA-4 antibody
•Any unresolved toxicity National Cancer Institute (NCI) CTCAE Version 4.03 Grade ≥ 2 from previous anticancer therapy with the exception of alopecia, vitiligo, and laboratory values defined in the inclusion criteria.
•Subjects with Grade ≥ 2 neuropathy will be evaluated on a case-by-case basis after consultation with the Sponsor Investigator
•Subjects with irreversible toxicity not reasonably expected to be exacerbated by treatment with tremelimumab (e.g., hearing loss) may be included after consultation with the sponsor-investigator
•Any concurrent chemotherapy, investigational product, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer related conditions (e.g., hormone replacement therapy) is acceptable. Note: Local treatment of isolated lesions, excluding target lesions, for palliative intent is acceptable (e.g., local surgery or radiotherapy)
•Radiation therapy within 14 days of first dose of study drug
•Major surgical procedure within 28 days prior to first dose of study treatment

Arms & Interventions

Tremelimumab

Tremelimumab 750 mg IV Day 1 of each 28 day cycle. Up to 7 cycles.

Intervention: Tremelimumab

Outcomes

Primary Outcomes

Objective Response Rate

Time Frame: Up to a maximum of 12 months

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD) \>= 20% increase in tumor burden relative to nadir or the appearance of one or more new lesions; Stable Disease (SD), not meet criteria for CR/PR/PD. ORR is defined as the proportion of all subjects with confirmed PR or CR according to RECIST 1.1.

Secondary Outcomes

Duration of Response(Up to a maximum of 24 months)
Overall Survival(Time of treatment start until death or date of last contact, up to a maximum of 42 months.)
Adverse Events(AE had been recorded from time of consent until 30 days after discontinuation of study drug or until a new anti-cancer treatment starts, whichever occurs first; up to a maximum of 13 months)
Disease Control Rate(Up to a maximum of 12 months)
Progression Free Survival (PFS)(Time of treatment start until the criteria for disease progression or death. Up to a maximum of 24 months.)