Title

ABC294640 in Treating Patients With Advanced Solid Tumors
A Phase I, Open-label, Dose-Escalation, Safety, Pharmacokinetic and Pharmacodynamic Study of ABC294640 in Patients With Advanced Solid Tumors
  • Phase

    Phase 1
  • Study Type

    Interventional
  • Status

    Completed No Results Posted
  • Intervention/Treatment

    abc-294640 ...
  • Study Participants

    22
This phase I trial studies the side effects and best dose of ABC294640 in treating patients with advanced solid tumors. ABC294640 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Please note that the FDA OOPD is participating as a funding source.
PRIMARY OBJECTIVES:

I. To assess safety and determine the maximum tolerated dose (MTD) and the dose limiting toxicities (DLT) of ABC294640 (sphingosine kinase-2 inhibitor ABC294640) in patients with solid organ tumors. (Part I) II. To assess the safety and tolerability of ABC294640 at the MTD in an expanded cohort of hepatocellular carcinoma (HCC) patients. (Part II)

SECONDARY OBJECTIVES:

I. To establish the dose of ABC294640 recommended for future phase II protocols. (Part I) II. To describe the pharmacokinetics of ABC294640 in patients with solid organ tumors. (Part I) III. To describe the effects of ABC294640 on plasma levels of sphingosine 1-phosphate in patients with solid organ tumors. (Part I) IV. To assess antitumor activity of ABC294640 in patients with solid organ tumors by objective radiographic assessment using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. (Part I) V. To describe the pharmacokinetics of ABC294640 in HCC patients. (Part II) VI. To describe the effects of ABC294640 on plasma levels of sphingosine 1-phosphate in HCC patients. (Part II) VII. To assess antitumor activity of ABC294640 in HCC patients by objective radiographic assessment using RECIST 1.1 criteria. (Part II)

OUTLINE: This is a dose-escalation study.

Patients receive sphingosine kinase-2 inhibitor ABC294640 orally (PO) twice daily (BID) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up monthly for 1 year.
Study Started
Aug 31
2011
Primary Completion
Aug 31
2014
Study Completion
Jul 31
2015
Last Update
Jan 07
2020

Drug sphingosine kinase-2 inhibitor ABC294640

Given PO Starting dose of ABC294640 250 mg once on day on Days 1-28 of each 28-day cycle. Subsequent cohort doses (if reached) are as follows: 250 BID, 500 BID, 750 BID, 1,000 BID, 1,500 BID, 2,000 BID, 2,500 BID

  • Other names: SK2 inhibitor ABC294640

Treatment (enzyme inhibitor therapy) Experimental

Patients receive sphingosine kinase-2 inhibitor ABC294640 PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Criteria

Inclusion Criteria:

PART I:
Patients with histologically confirmed solid organ carcinomas
Tumor progression after receiving standard/approved chemotherapy or as first-line therapy for malignancies where there is no standard therapy
One or more tumors measurable on computed tomography (CT) scan per RECIST 1.1
Eastern Cooperative Oncology Group (ECOG) performance status =< 2
Life expectancy of at least 3 months
Age > 18 years
Signed, written Institutional Review Board (IRB)-approved informed consent
A negative pregnancy test (if female)
Acceptable liver function:
Bilirubin =< 3 times upper limit of normal (ULN) (Common Terminology Criteria for Adverse Events [CTCAE] Grade 2 baseline)
Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]), alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT]) =< 3 x ULN (CTCAE Grade 1 baseline)
Serum creatinine =< 1.5 X ULN (CTCAE Grade 1 baseline)
Absolute neutrophil count >= 1000 cells/mm^3
Acceptable hematologic status:
Absolute neutrophil coun > 1000 cells/mm3
Platelet count >= 75,000 (plt/mm^3) (CTCAE Grade 1 baseline)
Hemoglobin >= 9 g/dL
Acceptable blood sugar control:
Fasting glucose value < 160 mg/dL (CTCAE Grade 1 baseline)
Urinalysis: No clinically significant abnormalities
Prothrombin time (PT) and partial thromboplastin time (PTT) =< 1.5 X ULN after correction of nutritional deficiencies that may contribute to prolonged PT/PTT
For men and women of child-producing potential, willingness to use of effective contraceptive methods during the study; if female (or female partner of male subject), is either not of childbearing potential (defined as postmenopausal for >= 1 year or surgically sterile [bilateral tubal ligation, bilateral oophorectomy or hysterectomy]) or practicing 1 of the following medically acceptable methods of birth control and agrees to continue with the regimen throughout the duration of the study:
Oral, implantable or injectable contraceptives for 3 consecutive months before the baseline/randomization visit
Total abstinence from sexual intercourse (>= 1 complete menstrual cycle before the baseline/randomization visit)
Intrauterine device (IUD)
Double barrier method (condoms, sponge, diaphragm or vaginal ring with spermicidal jellies or cream)
PART II:
To be eligible for inclusion in Part II, patients must meet the eligibility for Part 1 as well as the following:
Patients with histologically confirmed HCC for whom there is no standard/approved chemotherapy

Exclusion Criteria:

New York Heart Association Class III or IV, cardiac disease, myocardial infarction within the past 6 months, unstable arrhythmia, or evidence of ischemia on electrocardiogram (ECG)
Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy
Pregnant or nursing women; NOTE: Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; or abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
Treatment with radiation therapy, surgery, chemotherapy, or investigational therapy within one month prior to study entry
Unwillingness or inability to comply with procedures required in this protocol
Known infection with human immunodeficiency virus (HIV)
Serious nonmalignant disease (e.g., hydronephrosis, liver failure, or other conditions) that could compromise protocol objectives in the opinion of the Investigator and/or the Sponsor
Patients who are currently receiving any other investigational agent
Patients who are receiving drugs that are sensitive substrates of CYP450 1A2, 3A4, 2C9, 2C19 or 2D6, or strong inhibitors or inducers of all major CYP450 isozymes that cannot be stopped at least 7 days or 5 half-lives (whichever is longer) before starting treatment with ABC294640 and either replaced with another appropriate medication or not given for the duration of the clinical study
Patients who are currently taking Coumadin or Coumadin derivatives
Patients who have received any antineoplastic therapy within 1 month of starting treatment with ABC294640 or who have not adequately recovered from side effects and toxicities of previous antineoplastic therapy
No Results Posted