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Active Clinical Trials

Phase 1-2 Study of the Safety, Pharmacokinetics, and Preliminary Activity of ASTX660 in Subjects with Advanced Solid Tumors and Lymphomas

Active NCT:
02503423
West Penn Hospital
West Penn Hospital

Category:
Cancer - Blood
Sponsor: 
Astex Pharmaceuticals
Contact: 

For more information, please contact Rich Wonder by telephone at 412-578-4492, or email at Rich.Wonder@ahn.org or Melissa McMillen, RN, MSN by telephone at 412-578-4493 or email at Melissa.McMillen@ahn.org.

Phase 1-2 Study of the Safety, Pharmacokinetics, and Preliminary Activity of ASTX660 in Subjects with Advanced Solid Tumors and Lymphomas

Purpose: 

This is an open-label, dose-escalation Phase 1/2 study to assess the safety of ASTX660, determine the maximum tolerated dose (MTD), recommended Phase 2 dose (RP2D), and recommended dosing regimen, and to obtain preliminary efficacy, pharmacokinetic (PK), and target engagement data, in subjects with advanced solid tumors or lymphoma for whom standard life-prolonging measures are not available.

Inclusion Criteria:

  1. Able to understand and comply with the protocol and study procedures, understand the risks involved in the study, and provide written informed consent before any study-specific procedure is performed.
  2. Men and women 18 years of age or older.
  3. Subjects with histologically or cytologically confirmed advanced solid tumors or lymphoma that is metastatic or unresectable, and for whom standard life-prolonging measures are not available. Specific tumor types that will be selected for study in Phase 2 are detailed in the protocol.
  4. In the Phase 2 portion of the protocol only, subjects must have measurable disease according to RECIST v1.1, or evaluable disease that can be reliably and consistently followed.
  5. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
  6. Acceptable organ function, as evidenced by the following laboratory data:

    1. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <=2.0 * upper limit of normal (ULN).
    2. Total serum bilirubin <=1.5 * ULN
    3. Absolute neutrophil count (ANC):

      • Phase 1 and 2 (except Phase 2 subjects with known lymphoma) >=1500 cells/mm3
      • Phase 2 subjects with known lymphoma: >=1000 cells/mm3 (>750 cell/mm3 for subjects with lymphoma in bone marrow)
    4. Platelet count:

      • Phase 1 and 2 (except Phase 2 subject with known lymphoma) >=100,000 cells/mm3
      • Phase 2 subjects with known lymphoma: >= 50,000 cells/mm3; >=25,000 cells/mm3 for subjects with lymphoma in bone marrow
    5. Serum creatinine levels <= 1.5 * ULN, or calculated (by Cockcroft-Gault formula or other accepted formula) or measure creatinine clearance >=50 mL/min.
  7. Women of child-bearing potential must not be pregnant or breastfeeding and must have a negative pregnancy test at screening. Women of child-bearing potential and all men with female partners of child-bearing potential must be practicing 2 medically acceptable methods of birth control and must not become pregnant or father a child while receiving treatment with study drug and for at least 3 months after completing treatment.

Exclusion Criteria:

  1. Hypersensitivity to ASTX660, excipients of the drug product, or other components of the study treatment regimen.
  2. Poor medical risk because of systemic diseases (e.g. active uncontrolled infections) in addition to the qualifying disease under study.
  3. Life-threatening illness, significant organ system dysfunction, or other condition that, in the investigator's opinion, could compromise subject safety or the integrity of the study outcomes, or interfere with the absorption or metabolism of ASTX660.
  4. History of, or at risk for, cardiac disease, as evidenced by 1 or more of the following conditions:

    1. Abnormal left ventricular ejection fraction (LVEF; <50%) or echocardiogram ECHO or multiple gated acquisition scan (MUGA). [Applies to Phase 1 only; ECHO/MUGA scans are not performed in Phase 2.]
    2. Congestive cardiac failure of >= Grade 3 severity according to New York Heart Association (NYHA) functional classification defined as subjects with marked limitation of activity and who are comfortable only at rest.
    3. Unstable cardiac disease including angina or hypertension as defined by the need for overnight hospital admission within the last 3 months (90 days).
    4. History or presence of complete left bundle branch block, heart block, cardiac pacemaker or significant arrhythmia.
    5. Concurrent treatment with any medical that prolongs QT interval and may induce torsades de pointes, and which cannot be discontinued at least 2 weeks before treatment with ASTX660. [Applies to Phase 1 only].
    6. Personal history of long QTc syndrome or ventricular arrhythmias including ventricular bigeminy.
    7. Screening 12-lead ECG with measurable QTc interval (according to either Fridericia's or Bazett's correction) of >=470 msec).
  5. Known history of human immunodeficiency virus (HIV) infection, or seropositive results consistent with active hepatitis B virus (HBV) or active hepatitis C virus (HCV) infection.
  6. Grade 2 or greater neuropathy. [Applies to Phase 1 only].
  7. Known brain metastases, unless stable or previously treated.
  8. Known significant mental illness or other conditions such as active alcohol or other substance abuse that, in the opinion of the investigator, predisposes the subject to high risk of noncompliance with the protocol treatment or assessments.
  9. Prior anticancer treatments or therapies within the indicated time window prior to first dose of study treatment (ASTX660), as follows:

    • Cytotoxic chemotherapy or radiotherapy within 3 weeks prior and any encountered treatment-related toxicities (excepting alopecia) not resolved to Grade 1 or less [Phase 1] or Grade 2 or less [Phase 2].
    • Monoclonal antibodies within 4 weeks prior and any encountered treatment-related toxicities not resolved to Grade 1 or less [Phase 1] or Grade 2 or less [Phase 2].
    • Investigational drugs (small molecules or biologics) within the longer of 2 weeks or 5 half-lives prior to study treatment and any encountered treatment-related toxicities not resolved to Grade 1 or less [Phase 1] or Grade 2 or less [Phase 2].
Eligibility Criteria: 
Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No