A Drug Interaction Study of Tasisulam in Patients With Advanced Cancer or Lymphoma

NCT01185548 | Terminated Phase 1 Results

• 2 other identifiers: 13076H8K-MC-JZAR
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 5

Brief Summary

The purpose of this study was to assess the effect of tasisulam as an inhibitor of CYP2C9, using tolbutamide as a probe substrate. This study was to have 3 treatment periods, and continued access in an extension period. Period 1 is 4 days in length. Periods 2 and 3 are each approximately 28 days in length. Due to the early termination of the trial, only 1 Period 3 participant enrolled in the extension period before study termination.

Conditions

Lymphoma; Advanced Cancer

Keywords

Advanced or Metastatic Solid Tumors or Lymphoma

Outcome Measures

Primary Outcomes (1)

• Pharmacokinetics of Tolbutamide, Concurrent Dosing, Area Under the Curve (AUC 0-∞)

  AUC0-∞ is defined as the area under the concentration time curve from time 0 to infinity.

  Period 2 Predose; and 0.5, 1, 1.5, 2, 2.5, 3, 4, 4.5, 6, 8, 24, 48, 72, 120, 168, 336 hours post tolbutamide dose

Secondary Outcomes (3)

• Pharmacokinetics of Tolbutamide, Staggered Dosing in Period 3, Area Under the Curve (AUC 0-∞)

  Period 3 Predose; and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 24, 48, 96, and 264 hours post tolbutamide dose

• Pharmacokinetics of Tolbutamide, Maximum Concentration (Cmax)

  Period 1, 2, and 3 Predose; and 0.5, 1, 1.5, 2, 2.5, 3, 4, 4.5, 6, 8, 24, 48, 72, 96, 120, 168, 264, 336 hours post tolbutamide dose

• Pharmacokinetics of Tolbutamide, Observed Time at Maximal Concentration (Tmax)

  Period 1, 2, and 3 Predose; and 0.5, 1, 1.5, 2, 2.5, 3, 4, 4.5, 6, 8, 24, 48, 72, 96, 120, 168, 264, 336 hours post tolbutamide dose

Study Arms (1)

Tasisulam and Tolbutamide

EXPERIMENTAL

Three study periods and continued access to tasisulam every 28 days (except Period 1 which was tolbutamide only and lasted 4 days) until disease progression: Period 1: 500 milligram (mg) tolbutamide administered on Day 1. Period 2: 500 mg of tolbutamide and individualized tasisulam dose \[based on area under the curve albumin-corrected threshold (AUCalb)\]. The AUCalb is a surrogate marker for unbound tasisulam, and this dosing approach represents the maximum level of unbound tasisulam which may be achieved clinically, administered on Day 1. Period 3: Individualized tasisulam dose (based on AUCalb) administered on Day 1 and 500 mg tolbutamide administered on Day 4.

Drug: Tolbutamide; Drug: Tasisulam

Interventions

Tolbutamide DRUG

Administered orally

Tasisulam and Tolbutamide

Tasisulam DRUG

Administered intravenously

Also known as: LY573636

Tasisulam and Tolbutamide

Eligibility Criteria

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

You may qualify if:

• Have histologically or cytologically confirmed solid malignancy or lymphoma that is advanced and/or metastatic disease which has not responded to standard therapy or for which no standard therapy exists.
• Have given written informed consent prior to any study-specific procedures.
• Have a performance status of less than or equal to 1 on the Eastern Cooperative Oncology Group (ECOG) scale and an estimated life expectancy of greater than 12 weeks.
• Have discontinued all previous therapies for cancer, including chemotherapy, radiotherapy, cancer-related hormonal therapy, or other investigational therapy for at least 30 days (45 days for mitomycin-C or nitrosoureas) prior to study enrollment and recovered from the acute effects of therapy. Limited field radiotherapy is permitted (in consultation with the investigator).
• Have adequate organ function.
• Are reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures.
• Males and females with reproductive potential must agree to use medically approved contraceptive precautions during the trial and for 6 months following the last dose of study drug.
• Females with child-bearing potential must have had a negative serum pregnancy test less than 7 days prior to the first dose of study drug.

You may not qualify if:

• Have received treatment within 30 days of the initial dose of study drug with an experimental agent for noncancer indications that has not received regulatory approval for any indication.
• Have known allergies to tasisulam or related compounds.
• Have serious preexisting medical conditions.
• Show evidence of significant active neuropsychiatric disease or central nervous system (CNS) disease (for example, Alzheimer's disease or Parkinson's disease). Patients with active brain metastasis are excluded.
• Have current acute or chronic leukemia.
• Females who are pregnant or lactating.
• Have known positive test results in human immunodeficiency virus (HIV), hepatitis B surface antigen (HBSAg), or hepatitis C antibodies (HCAb).
• History of severe allergies or multiple adverse drug reactions.
• Are persons who have previously completed or withdrawn from this study or any other study investigating tasisulam.
• Have an abnormality in the 12-lead electrocardiogram (ECG) that, in the opinion of the investigator, increases the risks associated with participating in the study.
• Serious concomitant systemic disorder, including diabetes or active infection, incompatible with the study.
• Clinically significant cardiac symptomology.
• Patients being treated with warfarin.
• Patients being treated with sulfonylureas
• Regularly use drugs of abuse and/or show positive findings on urinary drug screening that is not in accordance with known/acceptable concomitant medication.

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (5)

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Cardiff, South Glamorgan, CF14 2TL, United Kingdom

Location

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Sheffield, Trent, S10 2SJ, United Kingdom

Location

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Leeds, West Yorkshire, LS9 7TF, United Kingdom

Location

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Leicester, LE1 5WW, United Kingdom

Location

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

London, WC1E 6BT, United Kingdom

Location

MeSH Terms

Conditions

Lymphoma

Interventions

Tolbutamide; N-((5-bromo-2-thienyl)sulfonyl)-2,4-dichlorobenzamide

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Sulfonylurea Compounds; Urea; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

800-545-5979

Study Officials

• Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

  Eli Lilly and Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

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: August 18, 2010
• First Posted: August 20, 2010
• Study Start: July 1, 2010
• Primary Completion: December 1, 2010
• Study Completion: December 1, 2010
• Last Updated: October 19, 2018
• Results First Posted: October 19, 2018

Record last verified: 2018-03

Locations

GB (5)