Leiomyosarcomas, Non-Small Cell Lung Cancer, Osteosarcoma, Ovarian Cancer, Pancreatic Cancer, Refractory Malignant Solid Neoplasm, Synovial Sarcomas
Conditions
Brief summary
This phase I trial studies the side effects and best dose of AOH1996 in treating patients with solid tumors that do not respond to treatment (refractory). AOH1996 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Detailed description
PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose (MTD) and the dose limiting toxicities (DLT) of AOH1996. II. To establish the recommended phase 2 dose of AOH1996. III. To establish the recommended phase 2 dose of AOH1996 when given in conjunction with a TKI for NSCLC. SECONDARY OBJECTIVES: I. To determine the pharmacokinetics of AOH1996. II. To evaluate for preliminary efficacy of AOH1996. III. To evaluate response rate and disease control rate in solid tumors. EXPLORATORY OBJECTIVE: I. To determine pharmacodynamics parameters (alteration of gammaH2AX, downregulation of Myc) of AOH1996. OUTLINE: This is a dose-escalation study. Patients receive AOH1996 orally (PO) twice daily (BID) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days.
Interventions
Given PO
Sponsors
City of Hope Medical Center
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Informed Consent and Willingness to Participate * 1\. Documented informed consent by the participant * 2\. Willingness to permit study team to obtain and use archival tissue, if already existing Age Criteria, Performance Status and Life Expectancy * 3\. Age: ≥ 18 years * 4\. ECOG performance status ≤ 2 * 5\. Life expectancy of \> 3 months Nature of Illness and Treatment History \_\_6. Patients with solid tumors failing standard therapies or patients refusing standard treatments (exception: Part B NSCLC combination (EGFR TKI + AOH1996) cohort: patients with stable disease or better on EGFR TKI for at least 2 months) Contraception \_\_7. Agreement by females and males of childbearing potential\* to use an adequate method of birth control (hormonal contraception is inadequate) or abstain from heterosexual activity for the course of the study through 30 days after the last dose of study medication. See Appendix B for guidelines. \- Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for \> 1 year (women only). Laboratory Criteria (to be performed within 14 days prior to Day 1) * 8\. ANC ≥ 1,500/mm3 * 9\. Platelets ≥ 100,000/mm3 : * 10\. Total serum bilirubin ≤ 1.5 x ULN * 11\. AST =\< 1.5 x ULN or =\< 3 x ULN with liver metastases * 12\. ALT =\< 1.5 x ULN or =\< 3 x ULN with liver metastases * 13\. Creatinine clearance of ≥ 60 mL/min per 24 hour urine or the Cockcroft-Gault * 14\. Women of childbearing potential (WOCBP): negative urine or serum pregnancy test If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
Exclusion criteria
Concomitant Medications/Therapies \_\_1. Dietary/herbal supplements * 2\. Other investigational products or chemotherapy. Exception: EGFR TKI in the NSCLC expansion cohort is allowed. * 3\. Warfarin * 4\. Current or planned use of agents contraindicated for use with strong CYP3A4 inducers * 5\. Strong inhibitors or inducers of CYP2C9 * 6\. Strong inhibitors or inducers of CYP3A Other Illnesses and Conditions * 7\. Issues with tolerating oral medication (e.g., inability to swallow pills, malabsorption issues, ongoing nausea or vomiting). * 8\. Women who are or are planning to become pregnant or breastfeed * 9\. Known allergy to any of the components within the study agents and/or their excipients. * 10\. No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for three years. * 11\. Intercurrent or historic medical condition that increases subject risk in the opinion of the Investigator. Eligibility may be revisited for intercurrent medical conditions once resolution/recovery is deemed adequate by the investigator (e.g. recovery from major surgery, completion of treatment for severe infection). Noncompliance \_\_12. Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics). \*\*Eligibility should be confirmed per institutional policies.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of adverse events (AEs) | Up to 30 days after last study drug is given | Toxicity and adverse events will be recorded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. All toxicities/AEs will be recorded from the initiation of protocol therapy through the follow-up period. |
| Dose limiting toxicities | Up to 28 days (cycle 1) | Toxicities will be graded according to NCI CTCAE version 4.0. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Response rate | Up to 2 years | Will be assessed using Response Evaluation Criteria in Solid Tumors version 1. Response rate will be estimated in the overall population and 95% exact confidence intervals will be estimated. |
| Progression-free survival | Assessed up to 2 years | Time to disease progression/ relapse or death as a result of any cause. |
| Overall survival | Assessed up to 2 years | Time to death as a result of any cause. |
| Time to treatment failure | Assessed up to 2 years | Time to treatment termination for any reason (progression, toxicity, death, patient preference). |
Countries
United States
Contacts
CONTACTVincent Chung, MD
PRINCIPAL_INVESTIGATORVincent Chung, MD
City of Hope Medical Center
Outcome results
None listed