A Tasisulam and Midazolam Drug Interaction Study in Cancer Patients

Phase 1

Terminated

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.

Recruitment & Eligibility

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.

Arm && Interventions

Group	Intervention	Description
Drug Interaction arm	Tasisulam	-
Drug Interaction arm	Midazolam	-

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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.
Number of Participants With Tumor Response	Baseline to Day 15 of Maintenance Period up to 3 months	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.
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.	Tasisulam is highly bound to albumin. AUCalb is a surrogate measure of exposure to unbound (free) tasisulam.

Locations (1): 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, France