CholangiocarcinomaPhase 2NCT03377179

A Study of ABC294640 Alone and in Combination With HCQ Sulfate in the Treatment of Advanced Cholangiocarcinoma

A Phase 2 study testing ABC294640 and Hydroxychloroquine Sulfate 200 MG in people with Cholangiocarcinoma and Cholangiocarcinoma Non-resectable, run by RedHill Biopharma Limited at 5 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Cholangiocarcinoma, Cholangiocarcinoma Non-resectable, Cholangiocarcinoma, Perihilar
What is being tested?: ABC294640 and Hydroxychloroquine Sulfate 200 MG
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 65 participants
Where: 5 sitesUnited States
Study dates: 7 Mar 2018to 21 Jun 2022
Phase: Phase 2
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

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Age ≥18 years.
Signed, written IRB-approved informed consent.
A negative pregnancy test (if female).
Acceptable liver and renal function:
Bilirubin ≤ 1.5 times upper limit of normal (CTCAE Grade 2 baseline)
AST (SGOT), ALT (SGPT) ≤ 2.5 x upper limit of normal (ULN),
Serum creatinine ≤ 1.5 X ULN (CTCAE Grade 1 baseline)
Albumin > 3.0 g/dL
Acceptable hematologic status:
Absolute neutrophil count ≥1000 cells/mm3
Platelet count ≥75,000 (plt/mm3) (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 have contributed to prolonged PT/PTT.
For men and women of child-producing potential, willingness to use effective contraceptive methods during the study. If female (or female partner of male patient), was either not of childbearing potential (defined as postmenopausal for ≥ 1 year or surgically sterile [bilateral tubal ligation, bilateral oophorectomy or hysterectomy]) or practicing one of the following medically acceptable methods of birth control and agreed 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.
Double barrier method (condoms, sponge, diaphragm or vaginal ring with spermicidal jellies or cream

Who cannot join

>2 previous systemic anti-neoplastic regimens for CCA.
Previously having 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. NOTE: If a woman became pregnant or suspects she is pregnant while participating in this study, she must inform her treating physician immediately.
Treatment with radiation therapy, surgery, chemotherapy, or investigational therapy within 28 days prior to study entry.

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Patients who had received any antineoplastic therapy > 28 days prior to starting treatment with ABC294640 and HCQ must have recovered from the reversible effects of prior antineoplastic therapy (with the exception of alopecia and Grade 1 neuropathy).
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 CYP450 1A2, 3A4, 2C9, 2C19 or 2D6, or strong inhibitors or inducers of all major CYP450 isozymes that could not have been stopped at least 7 days or 5 half-lives (whichever was longer) before starting treatment with ABC294640, could not have been replaced with another appropriate medication or not given for the duration of the clinical study must be discussed with the Medical Monitor in order to determine eligibility for the study.
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 funduscopic eye examinations.
History of allergic reactions attributed to compounds of similar chemical or biologic composition to HCQ.

Trial locations and contacts

5 sites in 1 country.

City, postcode or hospital

5 sites in 1 country

United States5 sites

Emory University
Atlanta, Georgia, 30322
MD Anderson Cancer Center
Houston, Texas, 77030
Mayo Clinic Cancer Center
Phoenix, Arizona, 85054
Mayo Clinic Cancer Center
Rochester, Minnesota, 55905
Huntsman Cancer Institute, University of Utah
Salt Lake City, Utah, 84103

Other trials in United States

About this study

Official title: A Phase 2 Study of ABC294640 Alone and in Combination With Hydroxychloroquine Sulfate in the Treatment of Patients With Advanced, Unresectable Intra-hepatic, Perihilar and Extra-Hepatic Cholangiocarcinoma

ABC-108 is a single-arm Phase IIA clinical study of ABC294640 (Yeliva ®, opaganib) alone and in combination with hydroxychloroquine sulfate (HCQ) in the treatment of cholangiocarcinoma (CCA). In Part 1 of this clinical study, all participants will be receiving ABC294640 and in Part 2 all participants will be receiving ABC294640 and HCQ to explore the drugs activity signal in CCA. The study drug, ABC294640 is an orally available inhibitor of the enzyme sphingosine kinase-2 (SK2). SK2 is 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. ABC294640 also inhibits proliferation and induces apoptosis of cholangiocarcinoma cell lines. Furthermore, in a recent Phase I trial, ABC294640 demonstrated clinical activity in CCA patients. HCQ, is an orally available, FDA approved therapy for the treatment of malaria as well as discoid and systemic lupus erythematosus and rheumatoid arthritis. It is also known as an inhibitor of autophagy, a pro-survival mechanism utilized by many cancers. Evidence indicates that inhibition of autophagy can increase the therapeutic activity of ABC294640 in CCA. In Part 1 of this study, ABC294640 will be continuously administrated orally, twice a day, in 28 day cycles. In Part 2, ABC294640 and HCQ will be continuously administrated orally (the safe and tolerable will be determined in the study) in 28 day cycles. Administration of drug/s in both parts of the study will continue until disease progression, unacceptable toxicity or voluntary withdrawal initiated by the participants or physician.

Read the detailed description

This is an open-label clinical study to explore the activity signal of ABC294640 and of ABC294640 and HCQ in adult subjects who have been diagnosed with unresectable cholangiocarcinoma either intra- perhilar or extra-hepatic. The study will be conducted at 5 sites in the USA.

For Part 1, a maximum of 39 participants evaluable for efficacy will be enrolled in the study. Eligible participants will receive ABC294640, 500 mg twice a day, continuously administered in 28 day cycles.

Part 2 will be a single-arm Phase IIA study identical to Part 1 but treatment will consist of both ABC294640 together with HCQ. Additionally, Part 2, will consist of two phases: Phase I: accelerate HCQ dose-escalation run-in starting with a HCQ dose of 200 mg QD (once a day). Based on safety results, patient cohorts will be expanded, and dosing will continue to 200 mg BID (twice a day), 400 mg BID and 600 BID. At the end of Part2, Phase I, it will be determined what is the safe and tolerable HCQ dose for Phase II.

For Part 2, up to 15 patients evaluable for safety and tolerability will be enrolled in Phase I component of Part 2; and 20 patients evaluable for efficacy in the Phase II component of Part 2. All eligible participants will receive ABC294640, 500 mg BID in addition to the determined HCQ dose, continuously administered in 28 day cycles.

In addition to physical, neurological and eye exams (eye exams only for participants receiving HCQ), blood and urine samples will be routinely collected for safety and to determine response to the study drugs. Participants will be radiographically assessed for disease status every 2 cycles of treatment.

Tumor biopsies, when accessible, will be obtained within 21 days prior to the beginning of treatment and again on the beginning of the second treatment cycle.

All participants will be followed every 2 months for progression and survival for a maximum of 24 months after the last patient has been entered to the study. Follow up procedures may include physical examination, laboratory work and radiographic tumor assessment.

Conditions: Cholangiocarcinoma, Cholangiocarcinoma Non-resectable, Cholangiocarcinoma, Perihilar, Cholangiocarcinoma, Extrahepatic, Cholangiocarcinoma, Intrahepatic
Being tested: ABC294640, Hydroxychloroquine Sulfate 200 MG
Keywords: Clinical Trial, Phase II, Multicenter Trials, Clinical Study, Clinical Trials, Non-Randomized, Oral capsule, Single arm, Anti-cancer, Anti-inflammatory, ABC294640, Yeliva ®, opaganib, Hydroxychloroquine Sulfate, HCQ, Autophagy
Medical subject headings: Cholangiocarcinoma, Klatskin Tumor

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

ABC294640Drug
Also called yeliva, opaganib
Two 250 mg capsules of ABC294640 will be taken twice daily
Hydroxychloroquine Sulfate 200 MGDrug
Also called HCQ
HCQ tablets will be taken at a dose that will be determined

Study groups in NCT03377179
Study group	Role	What they receive
ABC294640 +/- HCQ treatment	Experimental	Part 1: All participants will be receiving ABC294640, 500 mg twice a day (BID), continuously in 28 day cycles Part 2: All participants will be receiving ABC294640, 500 mg twice a day (BID) and HCQ at a determined level, continuously in 28 day cycles Receives: Drug: ABC294640; Drug: Hydroxychloroquine Sulfate 200 MG

What is being measured

The primary outcome is the main question the study is designed to answer.

Part1 - Determine Response Rate
To determine the response rate (RR) of CCA defined as objective responses (OR), i.e. complete and partial responses (CR, PR) plus stable disease (SD) of at least 4 months to treatment with ABC294640.
Measured: At least 4 months
Part 2 - Determine the Durable Disease Control Rate
To determine the Durable Disease Control Rate (DDCR) of CCA defined as Disease Control Rate (DCR) of at least 4 months duration to treatment with ABC294640 and HCQ
Measured: At least 4 months

Secondary outcomes (12)

Physical exam to include eye exams (the latter only for patients enrolled in Part 2) to measure safety and tolerability of ABC294640 alone and in combination with HCQ
A physical exam which will include weight measurment in kilograms will be performed in screening and on the beginning of each cycle of treatment till 30 day post treatment.
Measured: From screening phase, during beginning of each cycle of treatment, till 30 days after the end of treatment (an estimated median of 5 months)
A general neurological exam to measure safety and tolerability of ABC294640 alone and in combination with HCQ
A general neurological exam will be performed in screening and on the beginning of each cycle of treatment till 30 day post treatment.
Measured: From screening phase, during beginning of each cycle of treatment, till 30 days after the end of treatment (an estimated median of 5 months)
HADS score for depression and anxiety to measure safety and tolerability of ABC294640 alone and in combination with HCQ
HADS (Hospital Anxiety and Depression Scale) questionnaire will be utilized to monitor any alterations in the participant's anxiety and depression levels.
Measured: From screening, during each cycle of treatment, till the end of treatment (an estimated median of 4 months). Patient diaries will be filled on a daily basis during treatment.
ECOG performance score to measure safety and tolerability of ABC294640 alone and in combination with HCQ
ECOG (Eastern Cooperative Oncology Group) performance score to the participant's performance status and how it is impacting the daily living abilities.
Measured: From screening, during each cycle of treatment, till the end of treatment (an estimated median of 4 months). Patient diaries will be filled on a daily basis during treatment.
MMSE score to measure safety and tolerability of ABC294640 alone and in combination with HCQ
MMSE (Mini-Mental State Examination) questionnaire will be utilized for evaluating the mental state of the participants.
Measured: From screening, during each cycle of treatment, till the end of treatment (an estimated median of 4 months). Patient diaries will be filled on a daily basis during treatment.
Daily diary entries to aid in asessing safety and tolerability of ABC294640 alone and in combination with HCQ
Participants will be asked to fill a daily diary to record the drug administration and any side effects that they may experience.
Measured: From screening, during each cycle of treatment, till the end of treatment (an estimated median of 4 months). Patient diaries will be filled on a daily basis during treatment.
Number of treatment-related Adverse Events alone and in combination with HCQ
Adverse events will be graded according to the revised NCI Common Terminology Criteria for Adverse Events (NCI-CTCAE version 4.03) to measure the safety and tolerability of treatment with ABC294640 alone and in combination with HCQ in patients with unresectable CCA.
Measured: From screening till the 30 days after the end of treatment (an estimated median of 5 months)
The Maximum Plasma Concentration (Cmax) of ABC294640 and of HCQ
To determine the pharmacokinetics of ABC294640 (Part 1) and of ABC294640 and HCQ (Part 2) in the first 12 patients by measuring Maximum Plasma Concentration (Cmax) of ABC294640 and HCQ
Measured: From the first day of treatment until the beginning of second cycle of treatment (on day 1, 15, 28 approximately)
The Area Under the Curve (AUC) of ABC294640 (Part 1) and of ABC294640 and HCQ (Part 2)
To determine the pharmacokinetics of ABC294640 (Part 1) and of ABC294640 and HCQ (Part 2) in the first 12 patients by measuring the Area Under the Curve (AUC) of ABC294640 and of HCQ which reflects the body exposure to drug after administration of a dose of the drug.
Measured: From the first day of treatment until the beginning of second cycle of treatment (on day 1, 15, 28 approximately)
Determine the progression free survival (PFS)
Measured: Every 2 months for a maximum of 24 months after the last participant has been entered to the study
Determine Disease Control Rate (DCR=CR+PR+SD)
Determine Disease Control Rate (DCR) = complete response (CR)+ partial response (PR) + stable disease (SD)
Measured: Every 2 months for a maximum of 24 months after the last participant has been entered to the study
Determine the overall survival (OS)
Measured: Every 2 months for a maximum of 24 months after the last participant has been entered to the study

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

7 Mar 201821 Jun 2022

First posted19 Dec 2017
Study start7 Mar 2018
Primary completion21 Jun 2022
Study completion21 Jun 2022

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (4)Papers the sponsor has linked to this study.
Other trials for CholangiocarcinomaStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Model description: Part 1- single-arm Phase IIA study, all participants receiving ABC294640, continuously administered in 28 day cycles, until disease progression, unacceptable toxicity or voluntary withdrawal Enrollment in a two-stage design: 12 participants will be accrued, if none of those patients respond, registration will halt. If one or more patients respond, additional 27 patients evaluable for efficacy will be enrolled. Part 2- identical to Part 1 with the exceptions: co-treatment of both ABC294640 and HCQ and study will consist of two phases: Phase I, a hybrid accelerate dose escalation run-in starting at HCQ dose of 200 mg QD. Based on safety results, patient cohorts will be expanded and dosing will escalate up to 600 mg BID. Phase II, treatment with ABC294640 and HCQ at the Phase I determined dose. Up to 15 participants evaluable for safety and tolerability will be accrued in Phase I and 20 participants evaluable for efficacy in Phase II, Part 2.
Masking: None (open label)
Enrolment: 65 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03377179
Sponsor's protocol ID: ABC-108
Status last verified: Jul 2025
First submitted: 1 Dec 2017
Last updated: 23 Jul 2025
Results posted: No
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No
Expanded access: Available

Publications

Ding X, Chaiteerakij R, Moser CD, Shaleh H, Boakye J, Chen G, Ndzengue A, Li Y, Zhou Y, Huang S, Sinicrope FA, Zou X, Thomas MB, Smith CD, Roberts LR. Antitumor effect of the novel sphingosine kinase 2 inhibitor ABC294640 is enhanced by inhibition of autophagy and by sorafenib in human cholangiocarcinoma cells. Oncotarget. 2016 Apr 12;7(15):20080-92. doi: 10.18632/oncotarget.7914.
PubMed 26956050
Beljanski V, Knaak C, Smith CD. A novel sphingosine kinase inhibitor induces autophagy in tumor cells. J Pharmacol Exp Ther. 2010 May;333(2):454-64. doi: 10.1124/jpet.109.163337. Epub 2010 Feb 23.
PubMed 20179157
French KJ, Zhuang Y, Maines LW, Gao P, Wang W, Beljanski V, Upson JJ, Green CL, Keller SN, Smith CD. Pharmacology and antitumor activity of ABC294640, a selective inhibitor of sphingosine kinase-2. J Pharmacol Exp Ther. 2010 Apr;333(1):129-39. doi: 10.1124/jpet.109.163444. Epub 2010 Jan 8.
PubMed 20061445
Britten CD, Garrett-Mayer E, Chin SH, Shirai K, Ogretmen B, Bentz TA, Brisendine A, Anderton K, Cusack SL, Maines LW, Zhuang Y, Smith CD, Thomas MB. A Phase I Study of ABC294640, a First-in-Class Sphingosine Kinase-2 Inhibitor, in Patients with Advanced Solid Tumors. Clin Cancer Res. 2017 Aug 15;23(16):4642-4650. doi: 10.1158/1078-0432.CCR-16-2363. Epub 2017 Apr 18.
PubMed 28420720

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 23 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 2 Study of ABC294640 Alone and in Combination With Hydroxychloroquine Sulfate in the Treatment of Patients With Advanced, Unresectable Intra-hepatic, Perihilar and Extra-Hepatic Cholangiocarcinoma
ClinicalTrials.gov ID: NCT03377179
Acronym / sponsor ID: ABC-108
Conditions: Cholangiocarcinoma, Cholangiocarcinoma Non-resectable, Cholangiocarcinoma, Perihilar, Cholangiocarcinoma, Extrahepatic, Cholangiocarcinoma, Intrahepatic
Keywords: Clinical Trial, Phase II, Multicenter Trials, Clinical Study, Clinical Trials, Non-Randomized, Oral capsule, Single arm, Anti-cancer, Anti-inflammatory
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 65 participants (actual)
Lead sponsor: RedHill Biopharma LimitedIndustry (pharma, biotech, devices)
Study start: 7 Mar 2018 (actual)
Primary completion: 21 Jun 2022 (actual)
Study completion: 21 Jun 2022 (actual)
First posted: 19 Dec 2017 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Tumor biopsies, when accessible, will be obtained within 21 days prior to the beginning of treatment and again on the beginning of the second treatment cycle.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1
Model description: Part 1- single-arm Phase IIA study, all participants receiving ABC294640, continuously administered in 28 day cycles, until disease progression, unacceptable toxicity or voluntary withdrawal Enrollment in a two-stage design: 12 participants will be accrued, if none of those patients respond, registration will halt. If one or more patients respond, additional 27 patients evaluable for efficacy will be enrolled. Part 2- identical to Part 1 with the exceptions: co-treatment of both ABC294640 and HCQ and study will consist of two phases: Phase I, a hybrid accelerate dose escalation run-in starting at HCQ dose of 200 mg QD. Based on safety results, patient cohorts will be expanded and dosing will escalate up to 600 mg BID. Phase II, treatment with ABC294640 and HCQ at the Phase I determined dose. Up to 15 participants evaluable for safety and tolerability will be accrued in Phase I and 20 participants evaluable for efficacy in Phase II, Part 2.

Arm	Type	Receives
ABC294640 +/- HCQ treatment	Experimental	Drug: ABC294640, Drug: Hydroxychloroquine Sulfate 200 MGPart 1: All participants will be receiving ABC294640, 500 mg twice a day (BID), continuously in 28 day cycles Part 2: All participants will be receiving ABC294640, 500 mg twice a day (BID) and HCQ at a determined level, continuously in 28 day cycles

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (27 listed)

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.

Key exclusion criteria (17 listed)

>2 previous systemic anti-neoplastic regimens for CCA.
Previously having 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. NOTE: If a woman became pregnant or suspects she is pregnant while participating in this study, she must inform her treating physician immediately.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
ABC294640Also: yeliva, opaganibTwo 250 mg capsules of ABC294640 will be taken twice daily	Drug	ABC294640 +/- HCQ treatment
Hydroxychloroquine Sulfate 200 MGAlso: HCQHCQ tablets will be taken at a dose that will be determined	Drug	ABC294640 +/- HCQ treatment

Primary outcome

Part1 - Determine Response Rate
Time frame: At least 4 months
To determine the response rate (RR) of CCA defined as objective responses (OR), i.e. complete and partial responses (CR, PR) plus stable disease (SD) of at least 4 months to treatment with ABC294640.
Part 2 - Determine the Durable Disease Control Rate
Time frame: At least 4 months
To determine the Durable Disease Control Rate (DDCR) of CCA defined as Disease Control Rate (DCR) of at least 4 months duration to treatment with ABC294640 and HCQ

12 secondary outcomes

Physical exam to include eye exams (the latter only for patients enrolled in Part 2) to measure safety and tolerability of ABC294640 alone and in combination with HCQ
Time frame: From screening phase, during beginning of each cycle of treatment, till 30 days after the end of treatment (an estimated median of 5 months)
A general neurological exam to measure safety and tolerability of ABC294640 alone and in combination with HCQ
Time frame: From screening phase, during beginning of each cycle of treatment, till 30 days after the end of treatment (an estimated median of 5 months)
HADS score for depression and anxiety to measure safety and tolerability of ABC294640 alone and in combination with HCQ
Time frame: From screening, during each cycle of treatment, till the end of treatment (an estimated median of 4 months). Patient diaries will be filled on a daily basis during treatment.
ECOG performance score to measure safety and tolerability of ABC294640 alone and in combination with HCQ
Time frame: From screening, during each cycle of treatment, till the end of treatment (an estimated median of 4 months). Patient diaries will be filled on a daily basis during treatment.
MMSE score to measure safety and tolerability of ABC294640 alone and in combination with HCQ
Time frame: From screening, during each cycle of treatment, till the end of treatment (an estimated median of 4 months). Patient diaries will be filled on a daily basis during treatment.
Daily diary entries to aid in asessing safety and tolerability of ABC294640 alone and in combination with HCQ
Time frame: From screening, during each cycle of treatment, till the end of treatment (an estimated median of 4 months). Patient diaries will be filled on a daily basis during treatment.
Number of treatment-related Adverse Events alone and in combination with HCQ
Time frame: From screening till the 30 days after the end of treatment (an estimated median of 5 months)
The Maximum Plasma Concentration (Cmax) of ABC294640 and of HCQ
Time frame: From the first day of treatment until the beginning of second cycle of treatment (on day 1, 15, 28 approximately)
The Area Under the Curve (AUC) of ABC294640 (Part 1) and of ABC294640 and HCQ (Part 2)
Time frame: From the first day of treatment until the beginning of second cycle of treatment (on day 1, 15, 28 approximately)
Determine the progression free survival (PFS)
Time frame: Every 2 months for a maximum of 24 months after the last participant has been entered to the study
Determine Disease Control Rate (DCR=CR+PR+SD)
Time frame: Every 2 months for a maximum of 24 months after the last participant has been entered to the study
Determine the overall survival (OS)
Time frame: Every 2 months for a maximum of 24 months after the last participant has been entered to the study

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 23 Jul 2025.
Background: PubMed 26956050Ding X, Chaiteerakij R, Moser CD, Shaleh H, Boakye J, Chen G, Ndzengue A, Li Y, Zhou Y, Huang S, Sinicrope FA, Zou X, Thomas MB, Smith CD, Roberts LR. Antitumor effect of the novel sphingosine kinase 2 inhibitor ABC294640 is enhanced by inhibition of autophagy and by sorafenib in human cholangiocarcinoma cells. Oncotarget. 2016 Apr 12;7(15):20080-92. doi: 10.18632/oncotarget.7914.
Background: PubMed 20179157Beljanski V, Knaak C, Smith CD. A novel sphingosine kinase inhibitor induces autophagy in tumor cells. J Pharmacol Exp Ther. 2010 May;333(2):454-64. doi: 10.1124/jpet.109.163337. Epub 2010 Feb 23.
Background: PubMed 20061445French KJ, Zhuang Y, Maines LW, Gao P, Wang W, Beljanski V, Upson JJ, Green CL, Keller SN, Smith CD. Pharmacology and antitumor activity of ABC294640, a selective inhibitor of sphingosine kinase-2. J Pharmacol Exp Ther. 2010 Apr;333(1):129-39. doi: 10.1124/jpet.109.163444. Epub 2010 Jan 8.
Results publication: PubMed 28420720Britten CD, Garrett-Mayer E, Chin SH, Shirai K, Ogretmen B, Bentz TA, Brisendine A, Anderton K, Cusack SL, Maines LW, Zhuang Y, Smith CD, Thomas MB. A Phase I Study of ABC294640, a First-in-Class Sphingosine Kinase-2 Inhibitor, in Patients with Advanced Solid Tumors. Clin Cancer Res. 2017 Aug 15;23(16):4642-4650. doi: 10.1158/1078-0432.CCR-16-2363. Epub 2017 Apr 18.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Mitesh Borad, MD principal investigator

Mayo Clinic

5 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 27 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part1 - Determine Response Rate (time frame: At least 4 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03377179, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jul 2025.