Neoplasms

Digestive System Diseases

Gland and Hormone Related Diseases

All Conditions

Rare Diseases

Pancreatic Neoplasms

Pancreatic Cancer

All Drugs and Chemicals

Enzyme Inhibitors

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.

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

sphingosine kinase-2 inhibitor ABC294640

Carolyn Britten, MD

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.

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

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.

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.

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 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.

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.

Apogee Biotechnology Corporation

Medical University of South Carolina

FDA Office of Orphan Products Development

National Cancer Institute (NCI)

RedHill Biopharma Limited

Cholangiocarcinoma

Klatskin Tumor

Adenocarcinoma

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Bile Duct Cancer

Anti-Inflammatory Agents

ABC294640

Mark L Levitt, MD, PhD

Vered Katz Ben-Yair, MSc

This is an expanded access program (EAP) for eligible participants who do not qualify for participation in, or who are otherwise unable to access, the ongoing clinical trial ABC-108. This program is designed to provide access to ABC294640 (Yeliva ®) for treatment of cholangiocarcinoma (CCA) prior to approval by the local regulatory agency. Availability will depend on territory eligibility. Participating sites will be added as they apply for and are approved for the EAP. An oncologist must decide whether the potential benefit outweighs the risk of receiving an investigational therapy based on the individual patient's medical history and program eligibility criteria.

Expanded Access for the Treatment of Advanced Cholangiocarcinoma With ABC294640 (Yeliva ®)

Expanded Access to ABC-108, A Phase IIA Study of ABC294640 in the Treatment of Patients With Advanced,Unresectable Intra-hepatic, Perihilar and Extra-Hepatic Cholangiocarcinoma

Carcinoma, Hepatocellular

Liver Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Hematinics

Antineoplastic Agents

Liver Extracts

Sorafenib

Patients with advanced HCC who have experienced tumor progression with sorafenib will receive ABC294640.

ABC294640 500 mg orally twice daily (approximately 12 hours apart) continuously.

ABC294640 will be dosed under fasting conditions (at least 1 hour before or 2 hours after eating). A cycle is defined as 28 days.

Micheal Lilly, MD

This is a Phase II study of single agent ABC294640. Patients with advanced hepatocellular carcinoma (HCC) who have experienced tumor progression or unacceptable toxicity on single agent sorafenib will receive ABC294640 500 mg by mouth twice a day continuously. Patients will continue on study drug until the development of progressive disease per modified RECIST, intolerable toxicity, withdrawal of patient consent or other event as outlined in patient discontinuation.

A Phase II Study of ABC294640 as Monotherapy in Patients With Advanced Hepatocellular Carcinoma

A Phase II Study of ABC294640 in Patients With Advanced Hepatocellular Carcinoma Who Have Progressed on Sorafenib

Radiographic Assessment will be completed up to 28 days prior to registration and every 8 weeks (+/- 7 days) following registration until disease progression or other (e.g.toxicity, patient decision, etc). The baseline radiographic assessment will include CT or MRI of the chest, abdomen and pelvis. Subsequent imaging will include only those body regions that include measureable index lesions per modified RECIST. Radiographic assessments will be completed every 8 weeks (+/- 7 days). In regards to the end of treatment visit, if the patient is taken off study and already has radiographic documentation of progressive disease, completing the radiographic assessment at the end of treatment visit is not required per study. If the patient is taken off study for other reasons such as toxicity or patient decision, it is strongly recommended that a radiographic assessment be obtained.

Patients who have not progressed by the end of the follow-up will have their TTP values censored.

Survival times will be censored for patients lost to follow-up or still alive at the trial's termination.

Blood samples will be drawn. Plasma or PK analysis for ABC294640 will be collected on:

* Cycle 1 (each cycle is 28 days) Day 1 prior to and at 2 and 8 hours post ABC294640 dosing
* Prior to dosing on and at 2 hours post dose Cycle 1 Day 15
* Prior to dosing on Cycle 2 Day 1.

Scatterplots of percent change in target lesions versus change in marker levels will be constructed. Variable transformations will be considered as needed and Pearson or Spearman correlation coefficients will be constructed as appropriate. The sample size of 39 provides a minimum of 80% power to detect a correlation of at least ± 0.44 versus a null correlation of 0.

All AEs and SAEs whether volunteered by the subject, discovered by study personnel during questioning, or detected through physical examination, laboratory test, or other means will be reported appropriately. Each reported AE or SAE will be described by its duration (i.e., start and end dates), regulatory seriousness criteria if applicable, suspected relationship to the study, and actions taken. Adverse events will be coded by body system and summary of table with incidence rates of AEs will be generated. Severity, duration, investigator attributed relationship to study drug and adverse event outcomes will be reported.

Scatterplots of percent change in target lesions versus change in immune cell subsets will be constructed. Variable transformations will be considered as needed and Pearson or Spearman correlation coefficients will be constructed as appropriated. The sample size of 39 provides a minimum of 80% power to detect a correlation of at least ± 0.44 versus a null correlation of 0.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
ABC294640 in Treating Patients With Advanced Solid Tumors	NCT01488513	Pancreatic Canc... Unspecified Adu...	sphingosine kin...	18 Years -	RedHill Biopharma Limited
ABC294640 in Treating Patients With Advanced Solid Tumors	NCT01488513	Pancreatic Canc... Unspecified Adu...	sphingosine kin...	18 Years -	RedHill Biopharma Limited
Expanded Access for the Treatment of Advanced Cholangiocarcinoma With ABC294640 (Yeliva ®)	NCT03414489	Cholangiocarcin... Cholangiocarcin... Cholangiocarcin... Cholangiocarcin... Cholangiocarcin...	ABC294640	18 Years -	RedHill Biopharma Limited
A Phase II Study of ABC294640 as Monotherapy in Patients With Advanced Hepatocellular Carcinoma	NCT02939807	Carcinoma, Hepa...	ABC294640	18 Years -	Medical University of South Carolina
Expanded Access for the Treatment of Advanced Cholangiocarcinoma With ABC294640 (Yeliva ®)	NCT03414489	Cholangiocarcin... Cholangiocarcin... Cholangiocarcin... Cholangiocarcin... Cholangiocarcin...	ABC294640	18 Years -	RedHill Biopharma Limited

Spots Global Cancer Trial Database for abc294640

Every month we try and update this database with for abc294640 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for abc294640

Every month we try and update this database with for abc294640 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for abc294640 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.