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Official Title

A Phase I Study of OTS167PO, a MELK Inhibitor, to Evaluate Safety, Tolerability and Pharmacokinetics in Patients With Advanced Breast Cancer and Dose-Expansion Study in Patients With Triple Negative Breast Cancer

Phase
Phase 1
Sponsor
OncoTherapy Science, Inc.
Enrollment
70
Timeline
May 2017 → Sep 2027
About This Study

The purpose of this study is to determine the maximum tolerated dose (MTD) of OTS167 administered via oral capsule (PO) to patients with relapsed/refractory locally advanced or metastatic breast cancer.

Eligibility Criteria

Inclusion Criteria

  • 1Dose Escalation and Dose Expansion Cohorts
  • 2Patients must meet all of the following criteria to be eligible for participation in the study:
  • 3Female patients, ≥ 18 years of age at the time of obtaining informed consent.
  • 4Patients with a documented (histologically- or cytologically-proven) breast cancer that is locally advanced or metastatic.
  • 5Patients with a malignancy that is either relapsed/refractory to standard therapy or for which no standard therapy is available.
  • 6Patients with a malignancy that is currently not amenable to surgical intervention due to either medical contraindications or non-resectability of the tumor.
  • 7Patients with measurable or non-measurable disease according to the Response Evaluation Criteria In Solid Tumor (RECIST, v1.1).
  • 8Patients with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 (see APPENDIX B: Performance Status Evaluation).
  • 9Life expectancy of greater than or equal to 3 months.
  • 10Resolution of all chemotherapy-related or radiation-related toxicities to Grade 1 severity or lower, except for stable sensory neuropathy (less than or equal to Grade 2).
  • 11Patients who are either not of childbearing potential or who agree to use a medically effective method of contraception during the study and during 3 months after the last dose of study drug. (See Appendix H: Forms of contraception).
  • 12Patients with the ability to understand and give written informed consent for participation in this trial, including all evaluations and procedures as specified by this protocol.
  • 13Dose expansion Cohort - TNBC
  • 14Patients with conditions as follows:
  • 15ER \<10%, PR \<10% by IHC assay; And
  • 16HER2 negative based on ASCO CAP guideline
  • 17Patients with measurable disease according to the response evaluation criteria in TNBC (RECIST, v1.1)
  • 18Patients with measurable disease that can be easily accessed for biopsy.
  • 19Relapsed (recurrence or disease progression after achieving a documented clinical response to first- or second-line treatment) or refractory (disease progression while receiving first line or second line treatment). In the case of TNBC, prior initial therapy with at least one known active regimen for TNBC including, but not limited to, any combination of anthracyclines, taxanes, platinum agents, Ixabepilone, and/or cyclophosphamide is required.

Exclusion Criteria

  • 1Dose Escalation and Dose Expansion Cohorts Patients meeting any of the following criteria are ineligible for participation in the study.
  • 2Women who are pregnant or lactating. Women of child-bearing potential (WOCBP) not using adequate birth control see Appendix H: Forms of contraception.
  • 3Patients with known central nervous system (CNS) or leptomeningeal metastases not controlled by prior surgery, radiotherapy or requiring corticosteroids to control symptoms, or patients with symptoms suggesting CNS involvement for which treatment is required.
  • 4Patients with primary brain tumors.
  • 5Patients with any hematologic malignancy. This includes leukemia (any form), lymphoma, and multiple myeloma.
  • 6Patients with any of the following hematologic abnormalities at baseline. (Patients may have received a red blood cell product transfusion prior to study, if clinically warranted.):
  • 7Absolute neutrophil count (ANC) \< 1,500 per mm3
  • 8Platelet count \< 100,000 per mm3
  • 9Hemoglobin \< 8.0 gm/dL
  • 10Patients with any of the following serum chemistry abnormalities at baseline:
  • 11Total bilirubin ≥ 1.5 × the ULN for the institution value
  • 12AST or ALT ≥ 3 × the ULN for the institution value (≥ 5 × if due to hepatic involvement by tumor)
  • 13Creatinine ≥ 1.5 × ULN for the institution value (or a calculated creatinine clearance \< 60 mL/min/1.73 m2\* )
  • 14Patients with a significant active cardiovascular disease or condition, including:
  • 15Congestive heart failure (CHF)requiring therapy
  • 16Need for antiarrhythmic medical therapy for a ventricular arrhythmia
  • 17Severe conduction disturbance
  • 18Unstable angina pectoris requiring therapy
  • 19QTc interval \> 450 msec (males) or \> 470 msec (females)
  • 20QTc interval ≤ 300 msec
  • 21History of congenital long QT syndrome or congenital short QT syndrome
  • 22LVEF \< 50% as measured by echocardiography or MUGA scan
  • 23Uncontrolled hypertension (per the Investigator's discretion)
  • 24Class III or IV cardiovascular disease according to the New York Heart Association's (NYHA) Functional Criteria (see APPENDIX C: New York Heart Association's Functional Criteria).
  • 25Myocardial infarction (MI) within 6 months prior to first study drug administration
  • 26Patients with a known or suspected hypersensitivity to any of the components of OTS167.
  • 27Patients with a known history of human immunodeficiency virus (HIV) or active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV).
  • 28Patients with any other serious/active/uncontrolled infection, any infection requiring parenteral antibiotics, or unexplained fever \> 38ºC within 1 week prior to first study drug administration.
  • 29Patients with inadequate recovery from any prior surgical procedure, or patients having undergone any major surgical procedure within 4 weeks prior to first study drug administration.
  • 30Patients with any other life-threatening illness, significant organ system dysfunction, or clinically significant laboratory abnormality, which, in the opinion of the Investigator, would either compromise the patient's safety or interfere with evaluation of the safety of the study drug.
  • 31Patients with a psychiatric disorder or altered mental status that would preclude understanding of the informed consent process and/or completion of the necessary studies.
  • 32Patients with the inability or with foreseeable incapacity, in the opinion of the Investigator, to comply with the protocol requirements.
  • 33Any anti-neoplastic agent or monoclonal antibody therapy for the primary malignancy (standard or experimental) within 2 weeks prior to first study drug administration.
  • 34Radiotherapy with a wide field of radiation within 4 weeks or radiotherapy with a limited field of radiation for palliation within 1 week of the first dose of study treatment. If acute symptoms of radiation have fully resolved, the extent and timing of radiotherapy for eligibility can be discussed between Investigator and Sponsor.
  • 35Patients requiring surgery for the primary or metastatic primary malignancy.
  • 36Herbal preparations or related over the counter (OTC) preparations/supplements containing herbal ingredients within 1 week prior to first study drug administration and during study.
  • 37Systemic hormonal therapy which is not related to breast cancer treatment (standard or experimental) within 1 week prior to first study drug administration and during study. The following therapies are allowed:
  • 38Hormonal therapy (e.g., Megace) for appetite stimulation
  • 39Nasal, ophthalmic, inhaled, and topical glucocorticoid preparations
  • 40Oral replacement glucocorticoid therapy for adrenal insufficiency
  • 41Low-dose maintenance steroid therapy for other conditions (excluding steroid tapers for brain edema/metastases/radiation)
  • 42Hormonal contraceptive therapy (for WOCBP must be combined with non-hormonal contraceptive equivalent to a double-barrier method)
  • 43Any other investigational treatments during study. This includes participation in any medical device or therapeutic intervention clinical trials.
  • 44Dose expansion Cohort - TNBC
  • 45Patients with only lesions that cannot be accessed for biopsy.

Locations

8 sites participating in this study

Emory University, Winship Cancer Institute

Atlanta, Georgia 30322

Recruiting

Shipra Gandhi, MD, MS

Norwalk Hospital

Norwalk, Connecticut 06856

Completed

Kapi'olani Medical Center for Women & Children

Honolulu, Hawaii 96826

Recruiting

Naoto Ueno, MD, PhD, FACP

Data sourced from ClinicalTrials.govView on ClinicalTrials.gov →