Description:
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.
Related Conditions:
- Conventional Glioblastoma Multiforme
- Malignant Glioma
- Malignant Solid Tumor
Title
- Brief Title: A Study of PRT811 in Participants With Advanced Solid Tumors, Gliomas and Myelofibrosis
- Official Title: A Phase 1, Open-Label, Multicenter, Dose Escalation and Expansion Study of PRT811 in Subjects With Relapsed/Refractory Myelofibrosis, Advanced Solid Tumors and Recurrent High-Grade Gliomas
Clinical Trial IDs
- ORG STUDY ID:
PRT811-01
- NCT ID:
NCT04089449
Conditions
- Advanced Solid Tumor
- Recurrent Glioma
- Myelofibrosis
Interventions
Drug | Synonyms | Arms |
---|
PRT811 | | PRT811 |
Purpose
This is a Phase 1 dose-escalation study of PRT811, a protein arginine N-methyltransferase
(PRMT) 5 inhibitor, in subjects with advanced cancers, high-grade gliomas and myelofibrosis
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 and /or high-grade gliomas, and relapsed/refractory
myeloproliferative neoplasms [MPN]. The study will consist of 2 parts, a dose escalation part
evaluating subjects with advanced solid tumors 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, glioblastoma multiforme and myelofibrosis. 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.
Trial Arms
Name | Type | Description | Interventions |
---|
PRT811 | Experimental | PRT811 will be administered orally | |
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
- 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
- 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:
- Requirement of pharmacologic doses of glucocorticoids
- Prior allogeneic bone marrow transplant; autologous hematopoietic transplantation less
than 100 days since transplantation
- 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
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | To describe dose limiting toxicities (DLT) of PRT811 |
Time Frame: | Baseline through Day 21 |
Safety Issue: | |
Description: | Dose limiting toxicities will be evaluated through the first cycle |
Secondary Outcome Measures
Measure: | To describe the adverse event profile and tolerability of PRT811 |
Time Frame: | Baseline through approximately 2 years |
Safety Issue: | |
Description: | Adverse events as characterized by type, frequency, severity, timing, seriousness and relationship to study therapy |
Measure: | To describe the pharmacokinetic profile of PRT811 |
Time Frame: | 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 |
Safety Issue: | |
Description: | PRT811 pharmacokinetics will be calculated including the maximum observed plasma concentration |
Measure: | To describe any anti-tumor activity of PRT811 |
Time Frame: | Baseline through approximately 2 years |
Safety Issue: | |
Description: | Anti-tumor activity of PRT811 will be based on the measurement of objective responses |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Prelude Therapeutics |
Last Updated
November 7, 2019