ABC294640 in Treating Patients With Advanced Solid Tumors (ABC-101)

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2013 by Medical University of South Carolina
Sponsor:
Collaborators:
Apogee Biotechnology Corporation
Information provided by (Responsible Party):
Melanie Thomas, Medical University of South Carolina
ClinicalTrials.gov Identifier:
NCT01488513
First received: September 29, 2011
Last updated: November 21, 2013
Last verified: November 2013
  Purpose

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.


Condition Intervention Phase
Pancreatic Cancer
Unspecified Adult Solid Tumor, Protocol Specific
Drug: sphingosine kinase-2 inhibitor ABC294640
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I, Open-label, Dose-Escalation, Safety, Pharmacokinetic and Pharmacodynamic Study of ABC294640 in Patients With Advanced Solid Tumors

Resource links provided by NLM:


Further study details as provided by Medical University of South Carolina:

Primary Outcome Measures:
  • Maximum tolerated dose (MTD) defined as highest dose of ABC294640 at which 0 or 1 patient of 6 experiences a DLT. [ Time Frame: Patients will be followed until the point in time when no more than 1 of 6 patients has a Dose Limiting Toxicity (DLT) in cycle 1, and expected 54 days. ] [ Designated as safety issue: Yes ]
    MTD defined as the highest dose at which 0 or 1 patient of 6 experiences a DLT. The DLT rate will be estimated with its 95% confidence interval.

  • Safety assessed using the National Cancer Institute (NCI) Common Toxicity Criteria (CTC) version 4.0. [ Time Frame: Weekly during course 1, bi-weekly for all subsequent courses, and at the end of treatment study-- expected to occur at an average of 6 months from study start. ] [ Designated as safety issue: Yes ]
    Assessed using the National Cancer Institute (NCI) Common Toxicity Criteria (CTC) version 4.0. Adverse events (AEs) will be coded by body system and summary tables with incidence rates of adverse events will be generated. Descriptive statistics of AEs will be reported by doses and for subsets of patients with serious adverse events (SAEs), patients who discontinue due to AEs, and patients with related AEs.


Secondary Outcome Measures:
  • Pharmacodynamic parameters for sphingosine kinase-2 inhibitor ABC294640 [ Time Frame: Days 1 and 28 of cycle 1 collected at prior to dose, 1, 2, 4, 8, 12, 24 hours post drug administration. ] [ Designated as safety issue: No ]
    Area under the drug concentration over time curve (AUC), maximum concentration, minimum concentration, and time to maximum concentration will be calculated for each subject.

  • Pharmacodynamic parameters for sphingosine kinase-2 inhibitor ABC294640 [ Time Frame: Weekly during course 1, bi-weekly for all subsequent courses, and at the end of treatment study ] [ Designated as safety issue: No ]
    Pharmacodynamic parameters for ABC294640 action will include measurement of plasma levels of S1P, including absolute concentration at each sampling time and chance from baseline concentration at each sampling time after drug administration.

  • Tumor response rate [ Time Frame: Every 8 weeks ] [ Designated as safety issue: No ]
    All patients who have measureable disease according to RECIST 1.1, received at least one cycle of treatment, and have had disease re-evaluated will be included.


Estimated Enrollment: 45
Study Start Date: August 2011
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (enzyme inhibitor therapy)
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.
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 Name: SK2 inhibitor ABC294640

Detailed Description:

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 pancreatic cancer 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 pancreatic cancer patients. (Part II) VI. To describe the effects of ABC294640 on plasma levels of sphingosine 1-phosphate in pancreatic cancer patients. (Part II) VII. To assess antitumor activity of ABC294640 in pancreatic cancer 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 pancreatic cancer 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01488513

Locations
United States, South Carolina
Medical University of South Carolina Recruiting
Charleston, South Carolina, United States, 29425
Contact: Melanie B. Thomas    843-792-5329    thomasmb@musc.edu   
Principal Investigator: Melanie B. Thomas         
Sponsors and Collaborators
Medical University of South Carolina
Apogee Biotechnology Corporation
Investigators
Principal Investigator: Melanie Thomas Medical University of South Carolina
  More Information

No publications provided

Responsible Party: Melanie Thomas, Associate Professor, Medical University of South Carolina
ClinicalTrials.gov Identifier: NCT01488513     History of Changes
Other Study ID Numbers: CTO 101504, NCI-2011-02993, G04102-00
Study First Received: September 29, 2011
Last Updated: November 21, 2013
Health Authority: United States: Institutional Review Board
United States: Federal Government

Keywords provided by Medical University of South Carolina:
ABC294640
Apogee
ABC-10

Additional relevant MeSH terms:
Neoplasms
Pancreatic Neoplasms
Digestive System Diseases
Digestive System Neoplasms
Endocrine Gland Neoplasms
Endocrine System Diseases
Neoplasms by Site
Pancreatic Diseases

ClinicalTrials.gov processed this record on October 29, 2014