Neoplasms

Symptoms and General Pathology

All Conditions

Blood and Lymph Conditions

Immune System Diseases

Rare Diseases

Neoplasm Metastasis

Lymphoma

Lymphosarcoma

Adjuvants, Anesthesia

Central Nervous System Depressants

Psychotropic Drugs

All Drugs and Chemicals

Midazolam

Anesthetics

Hypnotics and Sedatives

Anti-Anxiety Agents

Anesthetics, Intravenous

Anesthetics, General

GABA Modulators

Neurotransmitter Agents

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.

Tasisulam

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

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)

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.

A Tasisulam and Midazolam Drug Interaction Study in Cancer Patients

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

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 is highly bound to albumin. AUCalb is a surrogate measure of exposure to unbound (free) tasisulam.

Eli Lilly and Company

Period 1 (7 days): 1.2 milligrams (mg) midazolam orally on Day 1.

Period 2 (28 days): Tasisulam intravenously to target area under the curve above the albumin corrected threshold (AUCalb) in the range of 1200 to 6400 hour\*micrograms per milliliter (h\*mcg/mL) on Day 1 and 1.2 mg midazolam orally on Day 8.

Tasisulam and Midazolam

Maintenance Period 1 (35 days): Tasisulam was dosed intravenously to target AUCalb in the range of 1200 to 6400 h\*mcg/mL on Day 1.

Tasisulam (M1)

Maintenance Period 2 (35 days): Tasisulam was dosed intravenously to target AUCalb in the range of 1200 to 6400 h\*mcg/mL on Day 1.

Tasisulam (M2)

Period 1 (7 days): 1.2 milligrams (mg) midazolam orally on Day 1.

Period 2 (28 days): Tasisulam intravenously to target area under the curve above the albumin corrected threshold (AUCalb) in the range of 1200 to 6400 hour\*micrograms per milliliter (h\*mcg/mL) on Day 1 and 1.2 mg midazolam orally on Day 8.

Maintenance Period (35 days): Tasisulam was dosed intravenously to target AUCalb in the range of 1200 to 6400 h\*mcg/mL on Day 1.

Midazolam + Tasisulam

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

France

Region of Enrollment

All participants who received at least one dose of the study drug.

Chief Medical Officer

Period 2 (28 days): Tasisulam was dosed intravenously to target area under the curve above the albumin corrected threshold (AUCalb) in the range of 1200 to 6400 hour\*micrograms per milliliter (h\*mcg/mL) on Day 1 and followed by 1.2 mg midazolam orally on Day 8.

All participants who received study drug and had sufficient pharmacokinetics data to calculate AUC0-tlast. Analysis used data according to the treatment the participants actually received.

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

All participants who received study drug and had sufficient pharmacokinetics data to estimate Cmax. Analysis used data according to the treatment the participants actually received.

Midazolam Pharmacokinetics: Maximum Concentration (Cmax)

All participants who received study drug and had sufficient pharmacokinetics data to calculate AUC0-infinity. Analysis used data according to the treatment the participants actually received.

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

All participants who received study drug.

Number of Participants With Tumor Response

Period 2 (28 days): Tasisulam was dosed intravenously to target area under the curve above the albumin corrected threshold (AUCalb) in the range of 1200 to 6400 hour\*micrograms per milliliter (h\*mcg/mL) on Day 1 and followed by 1.2 milligrams (mg) midazolam orally on Day 8.

All participants who received tasisulam and had pharmacokinetics data.

Tasisulam Pharmacokinetics: Maximum Concentration (Cmax)

Period 2 (28 days): Tasisulam was dosed intravenously to target area under the curve above the albumin corrected threshold (AUCalb) in the range of 1200 to 6400 hour\*micrograms per milliliter (h\*mcg/mL) on Day 1 and followed by 1.2 milligrams (mg) midazolam orally on Day 8

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

Period 1 (7 days): 1.2 milligrams (mg) midazolam orally on Day 1.

Period 2 (28 days): Tasisulam intravenously to target area under the curve above the albumin corrected threshold (AUCalb) in the range of 1200 to 6400 hour\*micrograms per milliliter (h\*mcg/mL) on Day 1 and 1.2 mg midazolam orally on Day 8.

Maintenance Period 1 and 2 (35 days): Tasisulam was dosed intravenously to target AUCalb in the range of 1200 to 6400 h\*mcg/mL on Day 1.

Period 1

Period 2

Maintenance Period 1 (M1)

Maintenance Period 2 (M1)

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Hypoglycemic Agents

Tolbutamide

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.

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.

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

The Effect of Tasisulam on the CYP2C9-Mediated Metabolism of Tolbutamide: A Pharmacokinetic Interaction Study in Cancer Patients With Advanced and/or Metastatic Solid Tumors or Lymphoma

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

Adverse events (AEs) that occurred during Period 1 and during Period 2 when 500 mg tolbutamide was administered orally prior to individualized intravenous dosing (based on AUCalb) of tasisulam.

AEs that occurred during Periods 2 and 3 when both 500 mg oral tolbutamide and individualized intravenous tasisulam (based on AUCalb) were administered.

Tasisulam and Tolbutamide

AEs that occurred during Period 3 Day 1 through Day 4 until just before 500 mg oral tolbutamide was administered on Day 4, 72 hours.

Three study periods: Period 1 which was tolbutamide only and lasted 4 days and Periods 2 and 3 which had continued access to tasisulam every 28 days until disease progression:

Period 1: 500 mg tolbutamide administered once on Day 1.

Period 2: 500 mg of tolbutamide and individualized tasisulam dose administered once on Day 1.

Period 3: individualized tasisulam dose administered once on Day 1 and 500 mg tolbutamide administered once on Day 4.

All Participants

Age, Categorical

United Kingdom

All participants were included in the analysis.

Period 2: 500 mg of tolbutamide and individualized tasisulam dose (based on AUCalb) administered once on Day 1

Period 2: Tasisulam and Tolbutamide

All enrolled participants who started Period 2 (tasisulam and tolbutamide).

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

Period 3: Individualized tasisulam dose (based on AUCalb) administered once on Day 1 and 500 mg tolbutamide administered once on Day 4.

Tasisulam and Tolbutamide: Period 3

All enrolled participants who started period 3 (tasisulam then tolbutamide).

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

Period 1: 500 mg tolbutamide administered once on Day 1

Tolbutamide: Period 1

Period 2: 500 mg of tolbutamide and individualized tasisulam dose (based on AUCalb) administered once on Day 1.

Tasisulam and Tolbutamide: Period 2

Period 3: individualized tasisulam dose (based on AUCalb) administered once on Day 1 and 500 mg tolbutamide administered once on Day 4.

All enrolled participants who started Periods 1, 2, or 3.

Pharmacokinetics of Tolbutamide, Maximum Concentration (Cmax)

Period 1: Tolbutamide

Period 2: 500 mg tolbutamide and an individualized tasisulam dose (based on AUCalb) administered once on Day 1.

Period 3: Individualized tasisulam dose (based on AUCalb) administered once on Day 1 and 500 mg tolbutamide administered once on day 4 (administration day in period 3 could adjusted based on interim pharmacokinetic \[PK\] analyses)

Period 3: Tasisulam and Tolbutamide

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

Period 1: 500 milligram (mg) tolbutamide administered once on Day 1

Period 2: 500 mg of tolbutamide and individualized tasisulam dose (based on AUCalb) administered once on Day 1

Period 3: individualized tasisulam dose (based on AUCalb) administered once on Day 1 and 500 mg tolbutamide administered once on day 4

Period 1 : Tolbutamide

Skin and Connective Tissue Diseases

Melanoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

Tasisulam dose is dependent on participant's height, weight, and gender and is adjusted to target a specific Cmax based on participant laboratory parameters. Tasisulam is administered intravenously every 28 days until disease progression or other criteria for participant discontinuation are met.

tasisulam

The primary purpose of this study is to determine the objective response rate (complete and partial response) for participants who receive tasisulam after one prior systemic treatment for unresectable or metastatic melanoma.

Participants will receive a 2-hour intravenous infusion of study drug (tasisulam) once every 28 days. Radiological imaging scans will be performed before the first dose of study drug and then after every other treatment. Participants will be assessed for clinical progression at every visit and for response approximately every 56 days (every other cycle).

A Study of Tasisulam in Treating Participants With Malignant Melanoma

A Phase 2 Study of LY573636 Administered as an Intravenous Infusion on Day 1 of a 28-Day Cycle as Second-Line Treatment in Patients With Unresectable or Metastatic Melanoma

Participants achieved an objective response if they had a best overall response of complete response (CR) or partial response (PR). According to Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1), CR was the disappearance of all non-nodal target lesions, with the short axes of any target lymph node reduced to \<10 mm, the disappearance of all non-target lesions, and the normalization of tumor marker levels (if tumor markers were initially above the upper limit of normal); PR was defined as at least a 30% decrease in the sum of the diameters of target lesions (including the short axes of any target lymph node), taking as reference the baseline sum diameter. For each participant who is not known to have died or to have had objective progression of disease as of the data-inclusion cut-off date for a particular analysis, duration of tumor response was to be censored at the date of the participant's last objective tumor assessment prior to that cut-off date.

PFS was defined as the time from baseline until measured PD or death from any cause, whichever is first. According to Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1), PD was at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. In addition to the 20% relative increase, the sum must have also demonstrated an absolute increase of at least 5 millimeters (mm). The appearance of 1 or more new lesions and/or unequivocal progression of existing nontarget lesions was also considered progression. Participants without objectively determined PD, who were alive at the end of the follow-up period (or lost to follow-up), were censored on the date of the participant's last complete radiographic tumor assessment; if no baseline or post-baseline radiologic assessment was available, the participant was censored at the date of randomization.

Participants achieved disease control if they had a best overall response of PR, CR or SD. According to RECIST v1.1, CR was the disappearance of all non-nodal target lesions, with the short axes of any target lymph node reduced to \<10 mm, the disappearance of all non-target lesions, and the normalization of tumor marker levels (if tumor markers were initially above the upper limit of normal \[ULN\]); PR was defined as at least a 30% decrease in the sum of the diameters of target lesions (including the short axes of any target lymph node), taking as reference the baseline sum diameter. SD was neither sufficient shrinkage to qualify as PR nor sufficient increase to qualify as PD, taking as reference the smallest sum diameter since treatment started. Clinical Response Rate was calculated as the number of participants who were free from progression (CR+PR+SD) for ≥2 cycles/number of participants who received at least 1 dose of tasisulam.

OS was defined as time from baseline to the date of death from any cause. Participants who were alive at the end of the follow-up period (or lost to follow-up) were censored on the last date the participant was known to be alive.

The duration of response was measured from the date of CR or PR to first date of documented PD or death and was censored at the date of the last assessment for responders who remained alive and did not have documented PD.

Duration of SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of diameters while on study. SD is measured at the start of the study drug until progressive disease or death due to any cause, whichever is first. Censoring occurred if a participant did not have a complete baseline disease assessment, initiated on another anti-cancer therapy (censored at the date of the last complete objective progression-free disease assessment before initiation of the new therapy), was not known to have died or had objective progression as of the data inclusion cutoff date for analysis.

Data presented are the number of participants who experienced SAEs considered by the investigator to be related to study drug administration. A summary of SAEs and all other non-serious Adverse Event(s) (AEs), regardless of causality, is located in the Reported Adverse Event module.

FACT-G is a 27-item compilation of general questions divided into 4 primary health-related quality of life (HRQL) domains: Physical Well-Being, Social/Family Well-Being, Emotional Well-Being, and Functional Well-Being. Total scores ranged from 0 to 172; higher scores = better HRQL.

Tasisulam loading dose targeting 420 μg/mL maximum concentration at the end of infusion (Cmax) administered as a 2-hour intravenous (IV) infusion on Day 1 of Cycle 1, followed by a chronic dose of 65% of the loading dose on Day 1 of subsequent 21-day cycles (every three weeks).

Tasisulam Dose Target 420 μg/mL Cmax

Tasisulam loading dose targeting 360 μg/mL Cmax was administered as a 2-hour IV infusion on Day 1 of Cycle 1, followed by a chronic dose of 90% of the loading dose on Day 1 of subsequent 21-day cycles (every three weeks).

Tasisulam Dose Target 360 μg/mL Cmax

Tasisulam dose tailored to lean body weight (LBW) and pre-cycle albumin levels (≤420 μg/mL Cmax) was administered as a 2-hour IV infusion on Day 1 of Cycle 1, followed by chronic dosing ranging from 65% to 90% of the loading dose (tailored by the predose serum albumin for that cycle) on Day 1 of subsequent 28-day cycles (every four weeks).

Tasisulam Albumin-Tailored Dose

Total

United States

Australia

All enrolled participants who received at least one dose of study drug.

All participants who received at least one dose of study drug.

Percentage of Participants Achieving Objective Response Rate (ORR) (Complete Response + Partial Response)

All participants who received at least one dose of study drug. Participants censored: Tasisulam Target Cmax 420 µg/mL = 10, Tasisulam Target Cmax 360 µg/mL = 8, Albumin-Tailored Dose = 8.

Progression-Free Survival (PFS)

Percentage of Participants Achieving Complete Response (CR), Partial Response (PR), or Stable Disease (SD) (Clinical Response Rate)

Tasisulam dose is dependent on participant's height, weight, and gender and is adjusted to target a specific Cmax based on participant laboratory parameters. Participants will receive a 2-hour intravenous infusion of study drug once every 28 days.

All participants who received at least one dose of study drug and had evaluable PK data. PK analysis were performed on combined arms for total drug per protocol.

Pharmacokinetics: Plasma Clearance Rate of Tasisulam

All participants who received at least one dose of study drug. Participants censored: Tasisulam Target Cmax 420 µg/mL = 25, Tasisulam Target Cmax 360 µg/mL = 17, Albumin-Tailored Dose = 17.

Overall Survival (OS) Time

All participants who received at least one dose of study drug. Participants censored: Tasisulam Target Cmax 420 µg/mL = 1, Tasisulam Target Cmax 360 µg/mL = 1, Albumin-Tailored Dose = 0.

Duration of Overall Objective Response

All participants who received at least one dose of study drug. Participants censored: Tasisulam Target Cmax 420 µg/mL = 6, Tasisulam Target Cmax 360 µg/mL = 5, Albumin-Tailored Dose = 5.

Duration of Stable Disease (SD)

Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration (Safety: Adverse Events)

All participants who received at least one dose of study drug and had baseline and post baseline FACT-G data. FACT-G analysis was performed on combined arms per protocol.

Health-Related Quality of Life: Functional Assessment of Cancer Therapy-General (FACT-G) Score

Tasisulam loading dose targeting 420 micrograms/milliliter (μg/mL) maximum concentration (Cmax) at the end of infusion administered as a 2-hour intravenous (IV) infusion on Day 1 of Cycle 1, followed by a chronic dose of 65% of the loading dose on Day 1 of subsequent 21-day cycles (every three weeks).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Tasisulam and Midazolam Drug Interaction Study in Cancer Patients	NCT01209832	Advanced Cancer	Tasisulam Midazolam	18 Years -	Eli Lilly and Company
A Drug Interaction Study of Tasisulam in Patients With Advanced Cancer or Lymphoma	NCT01185548	Lymphoma Advanced Cancer	Tolbutamide Tasisulam	18 Years -	Eli Lilly and Company
A Study of Tasisulam in Treating Participants With Malignant Melanoma	NCT00383292	Metastatic Mela...	tasisulam	18 Years -	Eli Lilly and Company

Spots Global Cancer Trial Database for tasisulam

Every month we try and update this database with for tasisulam cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for tasisulam

Every month we try and update this database with for tasisulam cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for tasisulam cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.