Gamitrinib for the Treatment of Advanced or Refractory Solid Tumors or Lymphoma

Inclusion Criteria

• Patients with advanced, castration-resistant and metastatic prostate cancer as well as grade IV glioma, i.e. glioblastoma, will be especially encouraged to participate in the study, given the preclinical evidence of gamitrinib activity in these tumors.
• Histologically confirmed diagnosis of advanced cancer refractory to standard of care therapy, or for whom no standard of care therapy is available. Any numbers of prior therapies are allowed
• DOSE ESCALATION PHASE: Solid tumors and lymphoma may have measurable or evaluable disease as per Response Evaluation Criteria in Solid Tumors (RECIST version [v.] 1.1) or as per Response Evaluation Criteria In Lymphoma (RECIL) 2017 criteria
• DOSE EXPANSION PHASE: All patients must have at least one site of measurable disease as defined by RECIST v. 1.1. or RECIL 2017, for solid tumors and lymphoma, respectively
• DOSE EXPANSION PHASE: Patients in the expansion cohort must have at least one non-target lesion deemed safe to biopsy, in the opinion of the investigator, and be willing to undergo mandatory core biopsies. This includes pre-treatment and an on-treatment biopsy. Biopsies at the time of progression are highly desired, but optional.
• DOSE EXPANSION PHASE: The lesion(s) which will be used for response assessment may not be biopsied
• DOSE EXPANSION PHASE: Target lesions that have been previously irradiated will not be considered measurable unless increase in size is observed following completion of radiation therapy
• All previous therapies of cancer, including radiotherapy major surgery and investigational therapies must be discontinued for >= 14 days (>= 28 days for mitomycin C or nitrosoureas) before cycle 1 day 1 (C1D1), and all acute effects of any prior therapy must have resolved to baseline severity or grade =< 1 Common Terminology Criteria for Adverse Events (CTCAE v5), except alopecia or parameters defined in this eligibility list
• Age >= 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status 0- 2
• Absolute neutrophil count >= 1,500/mm^3 without growth factor use =< 7 days prior to C1D1
• Platelets >= 85,000/mm^3 without platelet transfusion =< 7 days prior to C1D1
• Hemoglobin > 8.5 g/dL without red blood cell transfusion =< 7 days prior to C1D1
• Total serum bilirubin < 1.5 X upper limit of normal (ULN) (except for patients with documented Gilbert’s syndrome for which total bilirubin must be < 3 mg/dL)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 2 X ULN; =< 5 X ULN if liver dysfunction is felt to be secondary to tumor burden
• Creatinine clearance >= 60 mL/min (per Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI 2021 formula])
• Serum or urine pregnancy test negative =< 7 days of C1D1 (women of childbearing potential [WOCBP] only)
• Ability to understand and willingness to sign a written informed consent, Health Insurance Portability and Accountability Act (HIPAA) consent document and comply with the study scheduled visits, treatment plans, laboratory tests and other procedures
• Female patients must be surgically sterile or be postmenopausal, or must agree to use effective contraception during the period of the trial and for at least 90 days after completion of treatment. Male patients must be surgically sterile or must agree to use effective contraception during the period of the trial and for at least 90 days after completion of treatment. The decision of effective contraception will be based on the judgment of the principal investigator or a designated associate

Exclusion Criteria

• Patients with symptomatic brain metastases are excluded. Patients with asymptomatic and treated central nervous system (CNS) metastases may participate in this trial. The patient must have completed any prior treatment for CNS metastases > 28 days prior to study entry, including radiotherapy or surgery. Concurrent use of steroids for the treatment of brain metastasis are not permitted
• Current treatment on another (therapeutic) clinical trial
• History of ventricular tachycardia, torsade des pointes, complete left bundle branch block or third degree heart block or corrected QT by Fridericia's Correction Formula (QTcF) > 470 milliseconds, regardless of gender, on a 12-lead electrocardiogram (ECG) during the screening period (based on mean of triplicate electrocardiogram [EKGs])
• Hypertension not adequately controlled with medications (> 150/100 mm Hg despite optimal medical therapy)
• Active bacterial fungal or viral infection including hepatitis B (hepatitis B virus [HBV]), hepatitis C (hepatitis C virus [HCV]), requiring treatment with IV antibiotic, IV anti-fungal, or anti-viral (testing is not required for eligibility) * Patients with treated hepatitis B or C, with no evidence of continued infection or requirement for antiviral medications, are permitted
• Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness (testing is not required for eligibility)
• Any of the following in the previous 6 months: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack or symptomatic pulmonary embolism
• Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, or in the judgment of the investigator would make the patient inappropriate for entry into the study
• Receiving or requiring the continued use of medications that are known to strongly inhibit or induce CYP3A4/5 as well as strong Pgp inhibitors. To participate in this study, such subjects should discontinue use of such agents for at least 2 weeks before cycle 1 day 1
• Pregnant or breast feeding
• Avoid the use of strong inhibitors and inducers of major cytochrome P450 enzymes and strong inhibitors of renal, hepatic and promiscuous transporters