A Tasisulam and Midazolam Drug Interaction Study in Cancer Patients

NCT01209832 | Terminated Phase 1 Results

• 3 other identifiers: 13074H8K-MC-JZAP2010-020090-16
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this study is to evaluate whether tasisulam acts as an inducer of CYP3A using midazolam as a sensitive and specific probe substrate of CYP3A. The study will also assess the safety and tolerability of tasisulam and midazolam given in combination and document any antitumor activity with tasisulam.

Conditions

Advanced Cancer

Keywords

Metastatic Tumors; Lymphoma

Outcome Measures

Primary Outcomes (3)

• Midazolam Pharmacokinetics: Area Under the Concentration-Time Curve From Time Zero to the Last Time Point With Measurable Concentrations (AUC 0-tlast)

  Period 1 and 2: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 9, 11, 24, 48, and 72 hours post-dose.

• Midazolam Pharmacokinetics: Maximum Concentration (Cmax)

  Period 1 and 2: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 9, 11, 24, 48, and 72 hours post-dose.

• Midazolam Pharmacokinetics: Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC 0-infinity)

  Period 1 and 2: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 9, 11, 24, 48, and 72 hours post-dose.

Secondary Outcomes (3)

• Number of Participants With Tumor Response

  Baseline to Day 15 of Maintenance Period up to 3 months

• Tasisulam Pharmacokinetics: Maximum Concentration (Cmax)

  Period 2: Predose, preinfusion start, 1, 1.75, 2 (post end of infusion), 2.5, 3, 4, 6, 8, 24, 48, 72, 120, 168, and 336 hours.

• Tasisulam Pharmacokinetics: Area Under the Concentration-Time Curve Above the Albumin Corrected Threshold (AUCalb)

  Period 2: Predose, preinfusion start, 1, 1.75, 2 (post end of infusion), 2.5, 3, 4, 6, 8, 24, 48, 72, 120, 168, and 336 hours.

Study Arms (1)

Drug Interaction arm

EXPERIMENTAL

Drug: Tasisulam; Drug: Midazolam

Interventions

Tasisulam DRUG

Patient specific dose, administered intravenously, on Day 1 of a 28-day cycle. Minimum of one (1) 28-day cycle. Patients may continue to receive tasisulam until disease progression or until discontinuation criteria are met.

Also known as: LY573636

Drug Interaction arm

Midazolam DRUG

1.2 milligrams (mg), administered orally once prior to the initiation of tasisulam therapy and once on Day 8 after initiation of tasisulam therapy

Drug Interaction arm

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 a performance status of less than or equal to 2 on the Eastern Cooperative Oncology Group (ECOG) scale
• 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 an estimated life expectancy, in the judgment of the investigator, of greater than or equal to 12 weeks

You may not qualify if:

• Have received treatment within 30 days of the initial dose of study drug with an experimental agent for non-cancer indications that has not received regulatory approval for any indication
• Have symptomatic central nervous system (CNS) malignancy or metastasis (screening not required). Patients with active brain metastasis are excluded
• Have current acute or chronic leukemia
• Patients who have clinically significant chronic obstructive pulmonary disease (COPD) or other respiratory diseases that may be at risk during periods of conscious sedation under midazolam
• Patients with a known history of obstructive sleep apnea, difficult intubation, or syndromes associated with airway abnormalities.

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (3)

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.

Bordeaux, 33076, France

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.

Lille, 59020, France

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.

Rennes, 35033, France

Location

MeSH Terms

Conditions

Neoplasm Metastasis; Lymphoma

Interventions

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

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic 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: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 23, 2010
• First Posted: September 27, 2010
• Study Start: September 1, 2010
• Primary Completion: January 1, 2011
• Study Completion: January 1, 2011
• Last Updated: March 18, 2019
• Results First Posted: March 18, 2019

Record last verified: 2018-12

Locations

FR (3)