Solid Tumors, Glioblastoma, Recurrent Malignant Gliomas
Conditions
Brief summary
The purpose of this study is to determine the safety, tolerability, and the maximum tolerated dose/recommended phase II dose of carboxyamidotriazole orotate (CTO) as a single agent in patients with advanced or metastatic solid tumors; in combination with oral Temodar® in patients with glioblastoma or other recurrent malignant gliomas; or in combination with oral Temodar® and radiation therapy in patients with newly diagnosed glioblastoma or other malignant gliomas.
Interventions
DRUGCTO
Oral administration daily for 28 day cycles; starting dose of CTO = 50 mg/m2
DRUGCTO and Temodar®
Oral administration of CTO daily for 28 day cycles, starting dose of CTO = 219 mg/m2. Temodar® administered orally at fixed dose of 150 mg/m2 daily for Days 1-5 in a 28 day cycle. Expansion Cohort of 6 patients on fixed dose of 600mg CTO/day Temodar® administered orally at fixed dose of 150 mg/m2 daily for Days 1-5 in a 28 day cycle
DRUGCTO, Temodar®, Radiation therapy
Oral administration of CTO daily for 28 day cycles; starting dose of CTO = 219 mg/m2 Temodar® administered orally at a dose of 75 mg/m2 daily during radiation therapy, then at 150mg/m2 for Days 1-5 of Cycle 1, and then up to 200 mg/m2 Days 1-5 of subsequent cycles Radiation: 3-dimensional conformal radiation therapy or, Radiation: intensity-modulated radiation therapy
Sponsors
Tactical Therapeutics, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
(Treatment Arm A) 1. Patients must have histologically-confirmed solid tumors that are advanced or metastatic, and refractory after standard therapy, or for which there is no standard therapy. 2. Patients must have measurable disease as defined by RECIST version 1.1. 3. Patients must have received prior anticancer therapy or not be eligible for any established conventional therapy whether surgical or pharmacologic. 4. Patients must have recovered from all acute adverse effects (excluding alopecia) of prior therapies to baseline or \<=grade 1 prior to study entry. 5. Patients must have a performance status of 0, 1, or 2. 6. Patients must be men and women \>=18 years of age. 7. Patients must have adequate bone marrow function, defined as an absolute neutrophil count \>=1.5 x 10\^9/L and a platelet count \>= 100 x 10\^9/L. 8. Patients must have adequate renal function, defined as serum creatinine \<= 1.2 mg/dL (if \> 1.2 mg/dL, a calculated creatinine clearance \[by the Cockcroft-Gault method\] must be \>=60 mL/min/1.73 m\^2). 9. Patients must have adequate hepatic function, defined as plasma total bilirubin \<=1.5 mg, alanine transaminase (ALT) and aspartate transaminase (AST) \<=2.5 X ULN. Patients with Gilbert's disease outside these limits are judged to be ineligible. 10. Female patients of childbearing potential must have a negative serum or urine pregnancy test result at time of pre-treatment screening. 11. Patients with reproductive potential must agree to use at least one form of barrier contraception prior to study entry and for up to 30 days beyond the last administration of study drug. 12. Patients must be judged to be capable by the Investigator of providing informed consent and must be willing to provide written informed consent prior to the start of any study specific procedures. 13. Patients should have a life expectancy of at least 12 weeks.
Exclusion criteria
(Treatment Arm A) 1. Patients may not have had prior chemotherapy, hormonal therapy, radiation therapy, or biologic therapy in the 4 weeks prior to study entry with the exception of mitomycin C or nitrosoureas, for which patients must be 6 weeks from prior treatment. For patients who have been treated with targeted therapy, 5 half-lives of that therapy (or 28 days, whichever is shorter) must have passed prior to enrollment in the study. 2. Patients may not have any concomitant condition that could compromise the objectives of this study and the patients' compliance and ability to tolerate this therapy and complete at least 2 cycles of therapy, including, but not limited to the following: * Congestive heart failure or uncontrolled angina pectoris, previous history of myocardial infarction within 1 year from study entry, uncontrolled hypertension, or dysrhythmias. * Active infection. * Unstable diabetes mellitus * Psychiatric disorder that may interfere with consent and/or protocol compliance. 3. Pregnant or breastfeeding women. 4. Patients with another malignancy in the past 3 years except: curatively treated non-melanoma skin cancer; or carcinoma in situ, of either cervix or breast, that does not require further treatment. 5. Patients with known HIV, HBV, or HCV infection. 6. Patients with an underlying diagnosis or disease state associated with an increased risk of bleeding. 7. Patients with central nervous system metastases. Baseline CT or MRI scan of brain is required only in the case of clinical suspicion of central nervous system metastases. Patients with evidence of brain involvement, leptomeningeal disease, or seizure disorder are also excluded. 8. Patients may not be treated with known CYP3A4 inhibitors or inducers. Inclusion and
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To determine the MTD/RD of single agent CTO in patients with advanced or metastatic solid tumors; or CTO in combination with Temodar® in patients with glioblastoma or other recurrent malignant gliomas | Duration of the study | To determine the highest tolerated dose of CTO, based on safety data and occurence of dose-limiting toxicity, in patients with advanced or metastatic solid tumors. In the second stage of the study, to determine the highest tolerated dose of CTO in combination with Temodar®, based on safety data and toxicity profile, in patients with glioblastoma or other recurrent malignant gliomas. In the third stage of the study, to determine the highest tolerated dose of CTO in combination with Temodar® and radiation therapy based on safety data and toxicity profile, in patients with newly diagnosed glioblastoma or other malignant gliomas. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Preliminary tumor response | after every 2 cycles | RECIST 1.1 (Arm A); Macdonald Criteria (Arms B and C) |
| Pharmacokinetics (maximum concentration, Tmax, AUC, T1/2, clearance, volume of distribution) | pre- and post-dose during cycle 1 | Plasma concentrations and PK parameters will be determined for single agent CTO (Arm A), or CTO in combination with Temodar® (Arm B); plasma concentrations and PK parameters will be determined for Temodar®, or CTO and Temodar® in combination with radiation therapy (Arm C). |
| Voluntary Exploratory objective | collected prior to enrollment | To investigate effect of CTO on tumor growth based on genotype |
| Exploratory Objective | Duration of study | To investigate effect of CTO alone and in combination with Temodar® on gene expression in scalp hair |
Countries
United States
Outcome results
None listed