To determine the recommended phase 2 dose (RP2D) of the combination of neratinib and sodium valproate when given to patients with advanced solid tumors. Then to explore the antitumor effects of the neratinib and sodium valproate combination in advanced solid tumors with attention to RAS-mutated tumors, EGFR-altered GBM, and ocular melanoma, as part of the phase 2 expansion cohort.
The purpose of this trial is to test the safety of combining 2 drugs, neratinib (Nerlynx) and divalproex sodium (Depakote DR), also commonly called valproate, when treating patients with advanced cancer. In an earlier stage of this trial the purpose was to test different doses of neratinib in combination with divalproex sodium to see which doses should be used in future research trials. This trial will also help us to learn how advanced tumors respond to the combination of neratinib and divalproex sodium.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
83
Combination of Neratinib and Divalproex Sodium (Valproate) will be given to patients with advanced solid tumors (dose escalation) and Ras-mutated cancers (dose expansion). Doses of Neratinib are escalated in small groups of patients during the dose expansion portion of the study.
Combination of Neratinib and Divalproex Sodium (Valproate) will be given to patients with advanced solid tumors (dose escalation) and Ras-mutated cancers (dose expansion).
Virginia Commonwealth University Massey Cancer Center
Richmond, Virginia, United States
RECRUITINGDetermination of Recommended Phase 2 Dose (RP2D)
RP2D for the combination of neratinib and sodium valproate that is less than or the same as the maximum tolerated dose (MTD).
Time frame: 28 Days
Evaluation of Treatment Related Adverse Events of Neratinib combined with Sodium Valproate
Determine the safety and toxicity of the combination of neratinib and sodium valproate by the number of participants with serious adverse events, and types of events as assessed by utilizing the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.
Time frame: 13 Months
Solid Tumor Antitumor Effects
Phase 2 advanced solid tumor cohorts only: Evaluate number of participants with tumor response based on Response Evaluation Criteria in Solid Tumors (RECIST v1.1), in patients evaluable for response.
Time frame: 13 Months
Glioblastoma Antitumor Effects
Phase 2 GBM cohort only: Evaluate number of participants with tumor control based on objective response based on Response Assessment in Neuro-Oncology (RANO) criteria or Macdonald criteria, or disease control defined as PFS ≥ 6-month in patients evaluable for response
Time frame: 13 Months
Progression Free Survival (PFS)
Evaluate the number of participants with progression free survival (PFS) defined as the duration of time from start of combination treatment (Cycle 1, Day 1) to date of progression.
Time frame: 13 Months
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.