ABC294640 in Treating Patients With Advanced Solid Tumors

NCT01488513 | Completed Phase 1 DMC

• 4 other identifiers: CTO 101504NCI -2011-02993G04102-00R01FD004102-01
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Pancreatic Cancer; Unspecified Adult Solid Tumor, Protocol Specific

Keywords

ABC294640; RedHill Biopharma, Ltd.; ABC-101; Medical University of South Carolina; Apogee Biotechnology Corporation

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose (MTD) defined as highest dose of ABC294640 at which 0 or 1 patient of 6 experiences a DLT.

  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.

  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.

• Safety assessed using the National Cancer Institute (NCI) Common Toxicity Criteria (CTC) version 4.0.

  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.

  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.

Secondary Outcomes (3)

• Pharmacodynamic parameters for sphingosine kinase-2 inhibitor ABC294640

  Days 1 and 28 of cycle 1 collected at prior to dose, 1, 2, 4, 8, 12, 24 hours post drug administration.

• Pharmacodynamic parameters for sphingosine kinase-2 inhibitor ABC294640

  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.

• Tumor response rate

  Every 8 weeks till end of treatment study-- expected to occur at an average of 6 months from study start.

Study Arms (1)

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.

Drug: sphingosine kinase-2 inhibitor ABC294640

Interventions

sphingosine kinase-2 inhibitor ABC294640 DRUG

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

Also known as: SK2 inhibitor ABC294640

Treatment (enzyme inhibitor therapy)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:

You may not qualify if:

• 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

Sponsors & Collaborators

• RedHill Biopharma Limited: lead
• Apogee Biotechnology Corporation: collaborator
• Medical University of South Carolina: collaborator
• FDA Office of Orphan Products Development: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

3-(4-chlorophenyl)-adamantane-1-carboxylic acid (pyridin-4-ylmethyl)amide

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Study Officials

• Carolyn Britten, MD

  Medical University of South Carolina

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 29, 2011
• First Posted: December 8, 2011
• Study Start: August 1, 2011
• Primary Completion: August 1, 2014
• Study Completion: July 1, 2015
• Last Updated: January 7, 2020

Record last verified: 2015-08

Locations

US (1)