A Phase 1b Trial in Patients With Renal Cell Cancer | NCT01258348

NCT01258348

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-JZAI	Other Identifier	Eli Lilly and Company

Status Module

Label	Type	Description	Intervention Names
LY573636 +sunitinib	Experimental		Drug: Drug: LY573636-sodium Drug: Sunitinib

Name	Type	Description	Arm Group Labels	Other Names
Drug: LY573636-sodium	Drug	Participant specific dose based on height, weight and gender to target a specific exposure range, administered intravenously on Day 4 of a 42-day (6-week) cycle. Dose will be escalated to reach the maximum tolerated dose (MTD). A cohort of participants enrolled after MTD will receive albumin-tailored doses. Participants may continue on treatment until clinical or objective disease progression.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Recommended Dose for Phase 2 Studies of LY573636-Sodium Combined With Sunitinib in Participants With Metastatic Renal Cell Carcinoma	Recommended Phase 2 dose was determined by maximum tolerated dose (MTD). MTD is the highest dose with <33% of participants having a dose-limiting toxicity (DLT) during the first 6-week cycle of treatment. DLT is an adverse event (AE) that is likely related to study drug or combination and fulfills any 1 of the following: Common Terminology Criteria for AE (CTCAE, Version 3.0) Grade (Gr) 4 neutropenia lasting ≥5 days; Gr 4 neutropenia with fever; Gr 4 thrombocytopenia; Gr ≥3 thrombocytopenia with bleeding; Gr ≥3 nonhematologic toxicity (excluding controllable nausea/vomiting or diarrhea and alopecia); Gr 3 electrolyte toxicity that is not resolved with standard treatments; Gr ≥3 elevated hepatic enzyme abnormalities in the setting of preexisting hepatic metastasis may not be considered a DLT; a DLT can be declared if a participant experiences increasing toxicity during treatment.	Predose up to 42 days postdose in Cycle 1 (6 weeks per cycle)

Secondary Outcomes

Measure	Description	Time Frame
Pharmacokinetics: Maximum Concentration (Cmax) of LY573636	Time frame: Cycle 1:day 4: pre-dose, start of infusion, end of infusion,30min,1h,2h,4h,6h,8h,10h,22h,46h,70h,166h,360h post infusion, day 25: predose, during infusion, end of infusion,30min,30min,1h,2h,4h,6h,8h,10h,22h,46h,70h,166h,360h post infusion.	Predose up to 2 hours postdose in Cycles 1 and 2 (6 weeks per cycle)

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Participants must have a histologically confirmed diagnosis of metastatic Renal Cell Carcinoma (RCC)
Participants must have received no prior treatment with a cytotoxic-based chemotherapy regimen
Participants must have measurable disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST) guidelines
Have adequate hematologic, hepatic and renal function
Have a serum albumin level greater than equal to 3.0 grams/Liter (g/L)
Participants with reproductive potential should use medically approved contraceptive precautions during the trial and for 6 months following the last dose of study drug
Exhibit participant compliance and geographic proximity that allow for adequate follow-up
Have given written informed consent approved by Lilly and the ethical review board (ERB)/institutional review board (IRB) governing the site
Have discontinued all previous therapies for cancer, including chemotherapy, radiotherapy, cancer-related hormonal therapy, or other investigational therapy, for at least 4 weeks (6 weeks for mitomycin-C or nitrosoureas) prior to study enrollment and recovered from the acute effects of therapy (except alopecia). Participants who have received whole-brain radiation must wait 90 days before starting study therapy

Exclusion Criteria:

Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry
Have received a prior cytotoxic chemotherapy-based systemic therapy for metastatic RCC
Have had any of the following within 12 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, congestive heart failure (CHF), cerebrovascular accident, transient ischemic attack, or pulmonary embolism
Ongoing cardiac arrhythmias greater than New York Health Association Class II (Protocol Attachment JZAI.4), atrial fibrillation of any grade, or prolongation of the QTc interval to greater than 450 milliseconds (msec) for males or greater than 470 msec for females
Have uncontrolled hypertension [greater than 150/100 millimeters of mercury (mm Hg) despite optimal medical therapy], or history of poor compliance with antihypertensive treatment
Participants with documented central nervous system or leptomeningeal metastasis (brain metastasis) at the time of study entry. Participants with signs or symptoms of neurological compromise should have appropriate radiographic imaging performed before study entry
Participants with serious concomitant OR pre-existing disorders, including active bacterial, fungal, or viral infection, incompatible with the study (at the discretion of the investigator)
Participants receiving warfarin therapy for treatment of venous thrombosis or other prothrombotic conditions
Participants with a second primary malignancy that could affect interpretation of the results. NOTE: Participants with adequately treated carcinoma of the skin (excluding melanoma) and participants with a prior history of malignancy who have been disease-free for greater than 2 years are eligible
Participants who have previously completed or withdrawn from this study or any other study investigating LY573636
Participants who have previously received sunitinib
Participants who are unable to swallow capsules
Participants who require concomitant use of potent Cytochrome P450 3A4 (CYP3A4) inducers or inhibitors
Women who are pregnant or lactating

Name	Affiliation	Role
Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon -Fri 9AM - 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.		Indianapolis	Indiana	46219

Arm/Group Information

ID	Title	Description
FG000	LY 340 μg/mL + Sunitinib 50 mg	LY573636 to target a maximum concentration (Cmax) of 340 micrograms per milliliter (μg/mL) (LY 340 μg/mL) as a 2-hour infusion on Days 4 and 25 of a 6-week cycle and sunitinib 50 milligrams (mg) orally, daily for 4 weeks followed by 2 weeks with no sunitinib dosing.
FG001	LY 300 μg/mL + Sunitinib 50/37.5 mg	LY573636 to target a Cmax of 300 μg/mL (LY 300 μg/mL) as a 2-hour infusion on Days 4 and 25 of a 6-week cycle and either sunitinib 50 mg orally, daily for 4 weeks followed by 2 weeks with no sunitinib dosing or sunitinib 37.5 mg daily continuously for 6 weeks .
FG002	LY 320 μg/mL + Sunitinib 37.5 mg	LY573636 to target a Cmax of 320 μg/mL (LY 320 μg/mL) as a 2-hour infusion on Day 4 of a 6-week cycle and sunitinib 37.5 mg orally, daily continuously for 6 weeks.
FG003	LY 340 μg/mL + Sunitinib 37.5 mg	LY573636 to target a Cmax of 340 μg/mL (LY 340 μg/mL) as a 2-hour infusion on Day 4 of a 6-week cycle and sunitinib 37.5 mg orally, daily continuously for 6 weeks.
FG004	LY 360 μg/mL + Sunitinib 37.5 mg	LY573636 to target a Cmax of 360 μg/mL (LY 360 μg/mL) as a 2-hour infusion on Day 4 of a 6-week cycle and sunitinib 37.5 mg orally, daily continuously for 6 weeks.

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	All Participants	LY573636 dose was to target a specific maximum concentration (Cmax) as a 2-hour infusion on Days 4 and 25 or Day 4 of a 6-week cycle. Sunitinib 50 milligrams (mg) orally, daily for 4 weeks followed by 2 weeks with no sunitinib dosing or sunitinib 37.5 mg daily continuously for 6 weeks.

Units	Counts
Participants	BG000

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

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 Dose for Phase 2 Studies of LY573636-Sodium Combined With Sunitinib in Participants With Metastatic Renal Cell Carcinoma

Recommended Phase 2 dose was determined by maximum tolerated dose (MTD). MTD is the highest dose with <33% of participants having a dose-limiting toxicity (DLT) during the first 6-week cycle of treatment. DLT is an adverse event (AE) that is likely related to study drug or combination and fulfills any 1 of the following: Common Terminology Criteria for AE (CTCAE, Version 3.0) Grade (Gr) 4 neutropenia lasting ≥5 days; Gr 4 neutropenia with fever; Gr 4 thrombocytopenia; Gr ≥3 thrombocytopenia with bleeding; Gr ≥3 nonhematologic toxicity (excluding controllable nausea/vomiting or diarrhea and alopecia); Gr 3 electrolyte toxicity that is not resolved with standard treatments; Gr ≥3 elevated hepatic enzyme abnormalities in the setting of preexisting hepatic metastasis may not be considered a DLT; a DLT can be declared if a participant experiences increasing toxicity during treatment.

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

Posted

Number

micrograms per milliliter (μg/mL)

Predose up to 42 days postdose in Cycle 1 (6 weeks per cycle)

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 340 μg/mL + Sunitinib 50 mg	LY573636 to target a maximum concentration (Cmax) of 340 micrograms per milliliter (μg/mL) (LY 340 μg/mL) as a 2-hour infusion on Days 4 and 25 of a 6-week cycle and sunitinib 50 milligrams (mg) orally, daily for 4 weeks followed by 2 weeks with no sunitinib dosing.

ID	Term
D000230	Adenocarcinoma
D002277	Carcinoma
D009375	Neoplasms, Glandular and Epithelial
D009370	Neoplasms by Histologic Type

ID	Term
D011758	Pyrroles
D001393	Azoles
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds

ID	Term
C534068	N-((5-bromo-2-thienyl)sulfonyl)-2,4-dichlorobenzamide
D000077210	Sunitinib

OG000	LY 340 μg/mL + Sunitinib 50 mg	LY573636 to target a maximum concentration (Cmax) of 340 micrograms per milliliter (μg/mL) (LY 340 μg/mL) as a 2-hour infusion on Days 4 and 25 of a 6-week cycle and sunitinib 50 milligrams (mg) orally, daily for 4 weeks followed by 2 weeks with no sunitinib dosing.
OG001	LY 300 μg/mL + Sunitinib 50/37.5 mg	LY573636 to target a Cmax of 300 μg/mL (LY 300 μg/mL) as a 2-hour infusion on Days 4 and 25 of a 6-week cycle and either sunitinib 50 mg orally, daily for 4 weeks followed by 2 weeks with no sunitinib dosing or sunitinib 37.5 mg daily continuously for 6 weeks .
OG002	LY 320 μg/mL + Sunitinib 37.5 mg	LY573636 to target a Cmax of 320 μg/mL (LY 320 μg/mL) as a 2-hour infusion on Day 4 of a 6-week cycle and sunitinib 37.5 mg orally, daily continuously for 6 weeks.
OG003	LY 340 μg/mL + Sunitinib 37.5 mg	LY573636 to target a Cmax of 340 μg/mL (LY 340 μg/mL) as a 2-hour infusion on Day 4 of a 6-week cycle and sunitinib 37.5 mg orally, daily continuously for 6 weeks.
OG004	LY 360 μg/mL + Sunitinib 37.5 mg	LY573636 to target a Cmax of 360 μg/mL (LY 360 μg/mL) as a 2-hour infusion on Day 4 of a 6-week cycle and sunitinib 37.5 mg orally, daily continuously for 6 weeks.