A Tasisulam and Midazolam Drug Interaction Study in Cancer Patients

Study Overview
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Brief Summary
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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.

Official Title
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The Effect of Tasisulam on CYP3A-mediated Metabolism of Midazolam: A Pharmacokinetic Interaction Study in Cancer Patients With Advanced and/or Metastatic Tumors or Lymphoma

Conditions
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Advanced Cancer

Intervention / Treatment
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* Drug: Tasisulam
* Drug: Midazolam


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Drug Interaction arm<br> | Drug: Tasisulam<br>* 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.<br>* Other names: LY573636;Drug: Midazolam<br>* 1.2 milligrams (mg), administered orally once prior to the initiation of tasisulam therapy and once on Day 8 after initiation of tasisulam therapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Tumor Response | Number of participants with tumor response = number of participants with complete response (CR) + number of participants with partial response (PR), as classified by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST) guidelines. CR is disappearance of all target and non-target lesions; PR is ≥30% decrease in sum of longest diameter of target lesions. | 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) | Tasisulam is highly bound to albumin. AUCalb is a surrogate measure of exposure to unbound (free) tasisulam. | 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. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metastatic Tumors, Lymphoma