Dose-Escalation Study of LY573636-sodium and Liposomal Do... | NCT01214668

NCT01214668

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

ID	Type	Description	Link
H8K-MC-JZAN	Other Identifier	Eli Lilly and Company

Status Module

Description Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Label	Type	Description	Intervention Names
LY573636 + Liposomal Doxorubicin	Experimental		Drug: LY573636-sodium Drug: Liposomal Doxorubicin

Interventions

Name	Type	Description	Arm Group Labels	Other Names
LY573636-sodium	Drug	Individualized dose is dependent on participant's height, weight, gender and is adjusted to target a specific exposure range corrected for a participant's laboratory parameters. Intravenous dosing is done on Day 1 of a 28-day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, cumulative dose of 550 milligrams per square meter (mg/m²) of liposomal doxorubicin or doxorubicin is reached, or other withdrawal criterion is met.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Recommended Phase 2 Dose	Recommended Phase 2 dose was determined by maximum tolerated dose (MTD), which is corrected for the participant's predose albumin to identify the albumin-corrected exposure range of LY 573636 when combined with liposomal doxorubicin. MTD is the highest dose with <33% of participants having a dose-limiting toxicity (DLT) in the first 28-day cycle of treatment. DLT is an adverse event (AE) that is likely related to the study drug or combination and fulfills any 1 of the following: Common Terminology Criteria for AE (CTCAE, Version 3.0) Grade (Gr) 4 hematologic toxicity; Gr 3 nonhematologic toxicity (excluding controllable nausea/vomiting or diarrhea and alopecia); Gr 3 electrolyte toxicity that is not resolved with standard treatments. Those who enter the study with Gr 2 hepatic enzyme abnormalities, DLT for an isolated Gr 3 hepatic enzyme abnormality is determined by investigators; a DLT can be declared if a participant experiences increasing toxicity during treatment.	Predose up to 28 days postdose in Cycle 1

Secondary Outcomes

Measure	Description	Time Frame
Number of Participants With Clinically Significant Events	Clinically significant events are defined as serious adverse events (SAEs), regardless of causality, during the study including the 30-day follow-up period. A summary of SAEs and other nonserious adverse events is located in the Reported Adverse Event section. Death due to progressive disease was not considered as an SAE.	Baseline to study completion up to 18.49 months

Other Outcomes

Measure	Description	Time Frame
Number of Participants Who Died Due to Progressive Disease During the 30 Days Following Discontinuation From Study Treatment		From date of randomization until up to 30 days post study treatment discontinuation, assessed up to 4.7 months

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

You must have a histologically confirmed solid malignancy that is unresectable and/or metastatic which has progressed after receiving standard approved chemotherapy
You must have a solid malignancy for which an anthracycline-based regimen is felt to be a reasonable treatment option
You must have measurable disease or non-measurable disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST)
You must have a serum albumin level greater than or equal to 3.0 grams/deciliter (g/dL) (30 g/L)
You must have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale
You must have tumor progression after receiving standard/approved chemotherapy
You must be reliable and willing to make yourself available for the duration of the study and are willing to follow study procedures
Women must be sterile, post-menopausal or on a contraception and men must be sterile or on contraception
Your test results assessing the function of your blood, kidneys, liver, and heart are satisfactory
Ovarian patients in the confirmation phase must have failed to achieve at least a partial response to a first-line platinum-based therapy (platinum-refractory) or have progression in less than 6 months after a response to a first-line platinum-based therapy (platinum-resistant)
Ovarian patients in the confirmation phase must have measurable disease by RECIST
Ovarian patients in the confirmation phase must be liposomal doxorubicin or doxorubicin naive and not amendable to curative therapy

Exclusion Criteria:

You cannot have received other investigational drugs within the last 28 days
You cannot have other on-going serious illnesses including active bacterial, fugal, or viral infections
You cannot have current hematologic malignancies, acute or chronic leukemia, or brain metastasis
You cannot currently be receiving warfarin (Coumadin®) therapy
You cannot have known positive test results in human immunodeficiency, hepatitis B surface antigen or hepatitis C antibodies
You cannot have a history of cardiac disease or clinical evidence of congestive heart failure
Ovarian patients in the confirmation phase who have received 2 or more cytotoxic regimens for platinum-resistant disease
You cannot currently be receiving amiodarone, quinidine, propofol, and clozapine
If you are taking esomeprazole or pantoprazole you must be able to stop taking this medication within 72 hours before and after LY573636 administration

Name	Affiliation	Role
Call 1-877-CTLILLY (1-877-285-4559) or 317-651-4559 Mon. - Fri. 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)	Eli Lilly and Company	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
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.		Scottsdale	Arizona	85258

Arm/Group Information

ID	Title	Description
FG000	LY 300 μg/mL + Dox	LY573636 targeting a maximum concentration (Cmax) of 300 micrograms per milliliter (μg/mL) (LY 300 μg/mL) as a 2-hour infusion on Day 1 of a 28-day cycle in combination with liposomal doxorubicin (Dox) at a dose of 40 milligrams per square meter (mg/m²) during the Dose-Escalation Phase.
FG001	LY 320 μg/mL + Dox	LY573636 targeting a Cmax of 320 μg/mL (LY 320 μg/mL) as a 2-hour infusion on Day 1 of a 28-day cycle in combination with liposomal doxorubicin (Dox) at a dose of 40 mg/m² during the Dose-Escalation Phase.
FG002	LY 340 μg/mL + Dox	LY573636 targeting a Cmax of 340 μg/mL (LY 340 μg/mL) as a 2-hour infusion on Day 1 of a 28-day cycle in combination with liposomal doxorubicin (Dox) at a dose of 40 mg/m² during the Dose-Escalation Phase.
FG003	LY 360 μg/mL + Dox	LY573636 targeting a Cmax of 360 μg/mL (LY 360 μg/mL) as a 2-hour infusion on Day 1 of a 28-day cycle in combination with liposomal doxorubicin (Dox) at a dose of 40 mg/m² during the Dose-Escalation Phase.
FG004	LY 380 μg/mL + Dox	LY573636 targeting a Cmax of 380 μg/mL (LY 380 μg/mL) as a 2-hour infusion on Day 1 of a 28-day cycle in combination with liposomal doxorubicin (Dox) at a dose of 40 mg/m² during the Dose-Escalation Phase.
FG005	LY Albumin and Day 15 PK Tailored + Dox	LY573636 dosing was given as a 2-hour infusion on Day 1 of a 28-day cycle in combination with liposomal doxorubicin (Dox) at a dose of 40 mg/m² during the Dose-Confirmation Phase. LY573636 dose was based on an albumin-corrected exposure (AUCalb) target range of 75th percentile of 3500 hourmicrograms per milliliter (hµg/mL) and the Cycle 1, Day 15 LY573636 total drug level (Day 15 pharmacokinetic [PK]) (LY Albumin and Day 15 PK Tailored).

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	LY 300 μg/mL + Dox	LY573636 targeting a maximum concentration (Cmax) of 300 micrograms per milliliter (μg/mL) (LY 300 μg/mL) as a 2-hour infusion on Day 1 of a 28-day cycle in combination with liposomal doxorubicin (Dox) at a dose of 40 milligrams per square meter (mg/m²) during the Dose-Escalation Phase.
BG001

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Recommended Phase 2 Dose

Recommended Phase 2 dose was determined by maximum tolerated dose (MTD), which is corrected for the participant's predose albumin to identify the albumin-corrected exposure range of LY 573636 when combined with liposomal doxorubicin. MTD is the highest dose with <33% of participants having a dose-limiting toxicity (DLT) in the first 28-day cycle of treatment. DLT is an adverse event (AE) that is likely related to the study drug or combination and fulfills any 1 of the following: Common Terminology Criteria for AE (CTCAE, Version 3.0) Grade (Gr) 4 hematologic toxicity; Gr 3 nonhematologic toxicity (excluding controllable nausea/vomiting or diarrhea and alopecia); Gr 3 electrolyte toxicity that is not resolved with standard treatments. Those who enter the study with Gr 2 hepatic enzyme abnormalities, DLT for an isolated Gr 3 hepatic enzyme abnormality is determined by investigators; a DLT can be declared if a participant experiences increasing toxicity during treatment.

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

Posted

Number

micrograms per milliliter (μg/mL)

Predose up to 28 days postdose in Cycle 1

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	LY 300 μg/mL + Dox	LY573636 targeting a maximum concentration (Cmax) of 300 micrograms per milliliter (μg/mL) (LY 300 μg/mL) as a 2-hour infusion on Day 1 of a 28-day cycle in combination with liposomal doxorubicin (Dox) at a dose of 40 milligrams per square meter (mg/m²) during the Dose-Escalation Phase.

ID	Term
C534068	N-((5-bromo-2-thienyl)sulfonyl)-2,4-dichlorobenzamide
C506643	liposomal doxorubicin

OG000	LY 300 μg/mL + Dox	LY573636 targeting a maximum concentration (Cmax) of 300 micrograms per milliliter (μg/mL) (LY 300 μg/mL) as a 2-hour infusion on Day 1 of a 28-day cycle in combination with liposomal doxorubicin (Dox) at a dose of 40 milligrams per square meter (mg/m²) during the Dose-Escalation Phase.
OG001	LY 320 μg/mL + Dox	LY573636 targeting a Cmax of 320 μg/mL (LY 320 μg/mL) as a 2-hour infusion on Day 1 of a 28-day cycle in combination with liposomal doxorubicin (Dox) at a dose of 40 mg/m² during the Dose-Escalation Phase.
OG002	LY 340 μg/mL + Dox	LY573636 targeting a Cmax of 340 μg/mL (LY 340 μg/mL) as a 2-hour infusion on Day 1 of a 28-day cycle in combination with liposomal doxorubicin (Dox) at a dose of 40 mg/m² during the Dose-Escalation Phase.
OG003	LY 360 μg/mL + Dox	LY573636 targeting a Cmax of 360 μg/mL (LY 360 μg/mL) as a 2-hour infusion on Day 1 of a 28-day cycle in combination with liposomal doxorubicin (Dox) at a dose of 40 mg/m² during the Dose-Escalation Phase.
OG004	LY 380 μg/mL + Dox	LY573636 targeting a Cmax of 380 μg/mL (LY 380 μg/mL) as a 2-hour infusion on Day 1 of a 28-day cycle in combination with liposomal doxorubicin (Dox) at a dose of 40 mg/m² during the Dose-Escalation Phase.
OG005	LY Albumin and Day 15 PK Tailored + Dox	LY573636 dosing was given as a 2-hour infusion on Day 1 of a 28-day cycle in combination with liposomal doxorubicin (Dox) at a dose of 40 mg/m² during the Dose-Confirmation Phase. LY573636 dose was based on an albumin-corrected exposure (AUCalb) target range of 75th percentile of 3500 hourmicrograms per milliliter (hµg/mL) and the Cycle 1, Day 15 LY573636 total drug level (Day 15 pharmacokinetic [PK]) (LY Albumin and Day 15 PK Tailored).