Study Name
ABC-108: Study of ABC294640 (Yeliva®, opaganib) Alone and in Combination with Hydroxychloroquine Sulfate in the Treatment of Patients with Advanced Cholangiocarcinoma
ClinicalTrials.gov Identifier (if applicable)
NCT03377179
Clinical Trial Category (check all that apply)
  • Beyond First Line Therapy
Study Center
Institution Name
MD Anderson
Institution Address
1515 Holcombe Blvd
City
Houston
State
Texas
Zip Code
77030
List additional Institutions (include address, phone number, and website)
Mayo Clinic Hospital
5777 E. Mayo Blvd
Phoenix, AZ 85054

Mayo Clinic
200 First Street SW
Rochester, MN 55905

Emory University
Atlanta, Georgia, United States, 30322
Contact: Tyra Gaines    404-712-3308    tgaine3@emory.edu

Huntsman Cancer Institute, University of Utah
Salt Lake City, Utah, United States, 84103
Contact: Cherie Peterson    801-587-5598    Cherie.peterson@hci.utah.edu
Contact: Ignacio Garrido-Laguna, MD    801-585-0255    Ignacio.garrido-laguna@hci.utah.edu
Principal Investigator: Ignacio Garrido-Laguna, MD

Study Contacts
Principal Investigator
Dr. Shubham Pant
P.I. Phone
(713) 794-1776
P.I. Email
MEscano@mdanderson.org
List additional Principal Investigators (include phone number and email)
Mayo Clinic, Arizona – Dr. Daniel Ahn
Mayo Clinic, Minnesota – Dr. Amit Mahipal
Study Coordinator
Michelle Escano
Study Coordinator Phone
(713) 794-1776
Study Coordinator Email
MEscano@mdanderson.org
List additional Study Coordinators (include phone number and email)
Mayo Clinic – Clinical Trials Office: 855-776-0015
OVERVIEW – in layman’s terms (150 words max)
ABC-108 is a clinical study of ABC294640 alone and in combination with hydroxychloroquine sulfate (HCQ) in the treatment of advanced, unresectable intra-hepatic, perihilar and extra-hepatic cholangiocarcinoma (CCA). Enrollment for Part 1 of this study, in which all participants received ABC294640 orally, twice a day, in 28 day cycles, was completed. In Part 2, all participants will receive both ABC294640 and HCQ. Participants will be monitored for safety and to determine response to the study drugs.

ABC294640 is an orally available inhibitor of the enzyme sphingosine kinase-2 (SK2), an innovative target for anti-cancer therapy because of its critical role in sphingolipid metabolism, which is known to regulate tumor cell death and proliferation. Laboratory work on CCA models along with the results of a Phase 1 study, provide data supporting the development of ABC294640 as a novel therapeutic for treatment of CCA, including in combinations of with autophagy inhibitors such as HCQ.

Enrollment
Recruiting, study planned to enroll up to 39 patients
Study Start Date
01/02/2018
Estimated Completion Date
01/03/2021
Purpose of the Study – in Layman’s Terms 
The goal his clinical research study is to learn if the study drug ABC294640 alone or in combination with HCQ can help to control advanced, unresectable intra-hepatic, perihilar or extra-hepatic cholangiocarcinoma (CCA). The safety of these drugs will also be studied.
Inclusion Criteria – Patients Must:
  • Patients with histologically confirmed intrahepatic, perihilar or extra-hepatic CCA
  • Patients with no more than 2 prior treatments with systemic anti-neoplastic therapy for CCA
  • The tumor is unresectable and not amenable to curative therapy
  • One or more tumors measurable on CT scan per RECIST 1.1
  • Eastern Cooperative Oncology Group (ECOG) performance status 0- 1
  • Life expectancy of at least 3 months
  • Age ≥18 years
  • Signed, written IRB-approved informed consent
  • A negative pregnancy test (if female)
  • Acceptable liver and renal function (as detailed in clinicaltrials.gov)
  • Acceptable hematologic status (as detailed in clinicaltrials.gov)
  • Acceptable blood sugar control (Fasting glucose value ≤ 160 mg/dL)
  • Urinalysis: No clinically significant abnormalities
  • Prothrombin time (PT) and partial thromboplastin time (PTT) ≤ 1.5 X ULN after correction of nutritional deficiencies that may have contributed to prolonged PT/PTT
  • For men and women of child-producing potential, willingness to use of effective contraceptive methods during the study (as detailed in clinicaltrials.gov)
Exclusion Criteria – Patients Must NOT:
  • >2 previous systemic anti-neoplastic regimens for CCA
  • Previously received ABC294640 or HCQ (or chloroquine) for the treatment of a malignancy
  • New York Heart Association Class III or IV, cardiac disease, myocardial infarction within the past 6 months, unstable arrhythmia, or evidence of ischemia on ECG
  • Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy
  • Pregnant or nursing women
  • Treatment with radiation therapy, surgery, chemotherapy, or investigational therapy within 28 days prior to study entry
  • Patients who have received any antineoplastic therapy > 28 days prior to starting treatment with ABC294640 and have not recovered from side effects and toxicities of previous therapy
  • Unwillingness or inability to comply with procedures required in this protocol
  • Known infection with human immunodeficiency virus
  • 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 were currently receiving any other investigational agent
  • Patients who were receiving drugs that were sensitive substrates of certain CYP450 izoymes that couldn’t have been replaced with other medication (as detailed in clinicaltrials.gov)
  • Patients who are taking warfarin, apixaban, argatroban or rivaroxaban
  • If the patient is to receive HCQ, pre-existing retinopathy
  • Known history of G-6-PD deficiency, porphyria or psoriasis
  • History of macular degeneration, visual field changes, retinal disease, or cataracts that would interfere with eye examinations during the study
  • History of allergic reactions due to agents of similar chemical or biologic composition to HCQ
REQUIRED TESTS PRIOR TO BEGINNING STUDY TREATMENT – in layman’s terms
  • History and physical exam to include neurologic and eye exams (the latter only for patients enrolled in Part 2)
  • Two questionnaires about mood and mental state
  • Vital signs (heart rate, breathing rate, and blood pressure), weight
  • Blood test to look at overall health and for a pregnancy test (if you are a woman who may be able to have children)
  • Electrocardiogram (ECG) to look at the electrical activity of the heart
  • Urine test
  • Radiographic scans using Computed Tomography (CT) scan or magnetic resonance imaging (MRI) to check the status of the disease
  • Core needle biopsy (CNB) if tumor is accessible
POTENTIAL COMMON SIDE-EFFECTS – in layman’s terms
  • Nausea
  • Fatigue
  • Vomiting
  • Diarrhea
  • Feeling of sleepiness or drowsiness
  • Muscle spasms
  • Hot flashes
  • Changes in taste
  • Dizziness
  • Acute kidney injury
  • Vision changes including visual disturbances and blurred vision
  • General change in mood and mood swings

HCQ

  • Stomach pain
  • Feeling sick or nauseous

Not common, but concerning:

  • Vision changes that may be caused due to damage to the retina
  • Heart effects, including cardiomyopathy (weakening of the heart muscle) and heart rhythm disturbances
  • Worsening of psoriasis and porphyria, if you suffer from either of these diseases
  • Proximal myopathy (muscle weakness) and neuropathy (nerve damage), resulting in weakness and/or numbness
  • Neurologic or psychiatric side effects, including suicidal thoughts
  • Hypoglycemia- low blood sugar