Clinical trial NCT04089449: A Study of PRT811 in Participants With Advanced Solid Tumors, CNS Lymphoma and Gliomas
Official title: A Phase 1, Open-Label, Multicenter, Dose Escalation and Expansion Study of PRT811 in Subjects With Advanced Solid Tumors, CNS Lymphoma, and Recurrent High-Grade Gliomas
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Tumor
Recurrent Glioma
Keywords: PRMT5
PRMT5 Inhibitor
Lead sponsor: Prelude Therapeutics
Sponsor class: INDUSTRY
First posted: 2019-09-13
Enrollment: 86
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This is a Phase 1 dose-escalation study of PRT811, a protein arginine N-methyltransferase (PRMT) 5 inhibitor, in subjects with advanced cancers and high-grade gliomas who have exhausted available treatment options. The purpose of this study is to define a safe dose and schedule to be used in subsequent development of PRT811.

Detailed description: This is a multicenter, open-label, dose-escalation, dose-expansion Phase 1 study of PRT811, a PRMT5 inhibitor, in subjects with advanced cancers without any approved or available treatment options including solid tumors, CNS lymphoma, and /or high-grade gliomas. The study will consist of 2 parts, a dose escalation part evaluating subjects with advanced solid tumors, CNS lymphoma, and/or high-grade glioma and a cohort expansion part which will evaluate the safety and efficacy of PRT811 in subjects with advanced solid tumors, and glioblastoma multiforme. For subjects, the study will include a screening phase, a treatment phase, and a post treatment follow-up phase. An end-of-study visit will be conducted within 30 days after the last dose of PRT811.

Eligibility criteria: Inclusion Criteria:

* Malignancies that are refractory to or intolerant of established therapies known to provide clinical benefit for the malignancy in question, or in the opinion of the Investigator, not be a candidate for such therapies
* Subjects must have recovered from the effects of any prior investigational system therapies
* For subjects with recurrent high-grade glioma or GBM, must have biopsy proven evidence (WHO Grade III or IV) and received external bean fractionated radiotherapy and at least 2 cycles of adjuvant temozolomide chemotherapy. Mutant Glioma must comply with biomarker defined enrollment criterias.
* For biomarker-selected solid tumors: must meet enrollment criteria
* Eastern Cooperative Oncology Group (ECOG) Performance Score of 0 or 1
* Adequate organ function (bone marrow, hepatic, renal, cardiovascular)
* Female subjects of childbearing potential must have a negative pregnancy test within 7 days of the start of treatment and must agree to use an effective method of contraception during the trial

Exclusion Criteria:

* Untreated concurrent malignancies or malignancies that have been in complete remission for less than one year
* Treatment with strong inhibitors of CYP3A4 for which there are no therapeutic substitutions
* Inflammatory disorders of the gastrointestinal tract, or subjects with GI malabsorption
* HIV positive; known active hepatitis B or C
* Known hypersensitivity to any of the components of PRT811

Primary outcomes:
measure: To describe dose limiting toxicities (DLT) of PRT811
timeFrame: Baseline through Day 21
measure: To determine the maximally tolerated dose (MTD)
timeFrame: Baseline through approximately 2 years
measure: To determine the recommended phase 2 dose (RP2D) and schedule of PRT811
timeFrame: Baseline through approximately 2 years
Secondary outcomes:
measure: To describe the adverse event profile and tolerability of PRT811
timeFrame: Baseline through approximately 2 years
measure: To describe the pharmacokinetic profile of PRT811
timeFrame: Cycle 1 (each cycle is 21 days) on Days 1, 8 and 14. For subsequent cycles, Day 1 of each cycle through the end of study treatment, an average of 6 months
measure: To describe any anti-tumor activity of PRT811
timeFrame: Baseline through approximately 2 years
Other outcomes:
Locations:
city: Denver
country: United States
facility: Sarah Cannon Research Institute at HealthONE
state: Colorado
city: New Haven
country: United States
facility: Yale- New Haven Hospital- Yale Cancer Center
state: Connecticut
city: Newark
country: United States
facility: Christiana Care Health Services, Christiana Hospital
state: Delaware
city: Lake Mary
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Augusta
country: United States
facility: Georgia Cancer Center at Augusta University
state: Georgia
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Saint Louis
country: United States
facility: Washington University School of Medicine - Siteman Cancer Center
state: Missouri
city: Columbus
country: United States
facility: The Ohio State University and Wexner Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: Thomas Jefferson University, Sidney Kimmel Cancer Center
state: Pennsylvania
city: Nashville
country: United States
facility: Tennessee Oncology
state: Tennessee
Study officials:
References: