Safety Study of rhuMAb 2C4 to Treat Advanced Solid Tumors | NCT00027027

NCT00027027

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

Status Module

Name	Type	Description	Arm Group Labels	Other Names
rhuMAb 2C4	Drug

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of Participants With an Adverse Event (AE), Serious Adverse Event (SAE), or Death	For this protocol, an AE is defined any untoward medical occurrence (e.g., sign, symptom, disease, syndrome, intercurrent illness, abnormal laboratory finding) that emerges or worsens relative to pretreatment baseline during the treatment or post-treatment periods, regardless of the suspected cause. For this protocol an SAE was defined as any AE that occurred at any dose if: It resulted in death (i.e., the AE caused or led to death), It was life threatening, It required or prolonged inpatient hospitalization, It was disabling, It resulted in a congenital anomaly/birth defect, It may have jeopardized the participant or may have required medical or surgical intervention to prevent one of the outcomes listed above. The primary cause of death for all reported cases was disease progression, and all of the deaths occurred following study discontinuation, with one death occurring within 4 weeks of the last treatment day.	Days 1, 2, 5, 8, and 15 of Cycle 1; Days 1, 8, and Week 3, of Cycles 2 and beyond up to 1 year and at the follow-up visit (4 weeks after last infusion)
Number of Participants With Dose-Limiting Toxicities (DLTs)	Incidence of DLTs defined as any Grade 3 or 4 major organ toxicity according to the National Cancer Institute Common Toxicity Criteria (NCI-CTC) Version 2 or any subjectively intolerable toxicity felt by the investigator to be related to rhuMAb 2C4. One participant in the 15.0 mg/kg dose group experienced a gastrointestinal hemorrhage on Day 16. This event was judged by the investigator to be related to study drug. The participant recovered in 3 days and continued to receive rhuMAb 2C4 beyond Cycle 2.This was the only DLT reported during the first two treatment cycles.	Day 1 of Cycles 1 and 2, and 24 hours after Cycle 2 infusion

Secondary Outcomes

Measure	Description	Time Frame
Pharmacokinetic Measurement of Area Under the Curve (AUC)	Mean rhuMAb 2C4 serum concentrations versus nominal time profiles for the first two treatment cycles are presented for AUC micrograms per milliliters (ug/mL) by day. A one-compartment model was used for the 0.5 mg/kg dose group, and a two-compartment model was used for the 2-15 mg/kg dose groups.	Days 1 (predose, 89 minutes following start of infusion and at 1.5, 4, and 8 hours postdose) 2, 5, 8 and 15 of Cycle 1; Days 1 (predose and 29 minutes following start of infusion) and 8 of Cycle 2

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Signed informed consent
Age >=18 years old
ECOG performance status of 0 or 1 (see Appendix F)
Life expectancy of >=12 weeks
Histologically documented, incurable, locally advanced or metastatic solid malignancies
Disease progression on or after standard effective therapy or a malignancy for which there is no standard therapy
At least one bi-dimensionally measurable lesion (>=2 cm [>=1 cm on spiral CT scan])
HER2-negative status as defined by fluorescence in situ hybridization (FISH) testing (only for subjects with breast cancer)
Use of an effective means of contraception for women of childbearing potential
Granulocyte count of >=1500/uL, platelet count of >=100,000/uL, and hemoglobin of >=9 g/dL
Serum bilirubin less than or equal to the upper limit of normal (ULN) and alkaline phosphatase, AST, and ALT <=2.5x ULN (ALT and AST <=5x ULN for subjects with liver metastases; alkaline phosphatase <=5x ULN for subjects with liver or bone metastases)
Serum creatinine less than or equal to ULN or creatinine clearance of >=60 mL/min
International normalized ratio (INR) of <1.3 and activated partial thromboplastin time (aPTT) of <1.5x ULN

Exclusion Criteria:

Pleural effusions, ascites, or bone lesions as the only manifestation of the current cancer
Symptomatic or untreated brain metastases
Prior chemotherapy, hormonal therapy (except for androgen-deprivation therapy for subjects with prostate cancer), radiotherapy, or immunotherapy within 4 weeks of Day 1 (within 6 weeks for nitrosoureas or mitomycin)
Prior treatment with Herceptin
Prior cumulative doxorubicin dose of >360 mg/m2 or the equivalent
History of other malignancies within 5 years of Day 1 except for adequately treated carcinoma in situ of the cervix or basal or squamous cell skin cancer
History of significant cardiac disease, unstable angina, congestive heart failure, myocardial infarction, or ventricular arrhythmia requiring medication
Ejection fraction of <50% or below the lower limit of normal determined by ECHO (Subjects who are unable to have ejection fraction evaluated by ECHO may have ejection fraction evaluated by a MUGA scan, although this must be discussed with the Medical Monitor prior to enrollment.)
Active infection requiring IV antibiotics
Uncontrolled hypercalcemia (>11.5 mg/dL)
Clinically important history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis
Known human immunodeficiency virus (HIV) infection
Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the subject at high risk from treatment complications
Major surgery or significant traumatic injury within 3 weeks of Day 1
Pregnancy or lactation
Inability to comply with study and follow-up procedures

Facility	Status	City	State	ZIP	Country	Contacts
Cedars-Sinai Medical Center		Los Angeles	California	90211	United States

Arm/Group Information

ID	Title	Description
FG000	rhuMAb 2C4: 0.5 Milligrams Per Kilogram (mg/kg)	Recombinant Humanized Antibody to human epidermal growth factor receptor 2 (rhuMAb 2C4) 0.5 mg/kg was administered once every 3 weeks as an intravenous (IV) infusion until progressive disease (PD) or unacceptable toxicity occurred for up to a maximum of 1 year.
FG001	rhuMAb 2C4: 2 mg/kg	rhuMAb 2C4 2 mg/kg was administered once every 3 weeks as an IV infusion until PD or unacceptable toxicity occurred for up to a maximum of 1 year.
FG002	rhuMAb 2C4: 5 mg/kg	rhuMAb 2C4 5 mg/kg was administered once every 3 weeks as an IV infusion until PD or unacceptable toxicity occurred for up to a maximum of 1 year.
FG003	rhuMAb 2C4: 10 mg/kg	rhuMAb 2C4 10 mg/kg was administered once every 3 weeks as an IV infusion until PD or unacceptable toxicity occurred for up to a maximum of 1 year.
FG004	rhuMAb 2C4: 15 mg/kg	rhuMAb 2C4 15 mg/kg was administered once every 3 weeks as an IV infusion until PD or unacceptable toxicity occurred for up to a maximum of 1 year.

Periods

Title

Milestones

Reasons Not Completed

Overall Study

Type	Comment	Milestone Data
STARTED		FG0003 subjects FG0013 subjects FG0024 subjects FG0033 subjects FG0048 subjects
Discontinued Before 2 Treatment Cycles		FG0000 subjects FG0010 subjects FG0021 subjects FG0030 subjects
Completed 2 Cycles of Treatment		FG0003 subjects FG0013 subjects FG0023 subjects FG0033 subjects FG004
Discontinued at Cycle 2		FG0002 subjects FG0012 subjects FG0021 subjects FG0031 subjects FG004
Treated Beyond Cycle 2		FG0001 subjects FG0011 subjects FG0022 subjects FG0032 subjects FG004
COMPLETED		FG0000 subjects FG0010 subjects FG0020 subjects FG0030 subjects FG004
NOT COMPLETED		FG0003 subjects FG0013 subjects FG0024 subjects FG0033 subjects FG004

Type	Comment	Reasons
Adverse Event		FG0000 subjects FG0010 subjects FG0021 subjects FG003

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	rhuMAb 2C4: 0.5 mg/kg	rhuMAb 2C4 0.5 mg/kg was administered once every 3 weeks as an IV infusion until PD or unacceptable toxicity occurred for up to a maximum of 1 year.
BG001	rhuMAb 2C4: 2 mg/kg

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

Number of Participants With an Adverse Event (AE), Serious Adverse Event (SAE), or Death

For this protocol, an AE is defined any untoward medical occurrence (e.g., sign, symptom, disease, syndrome, intercurrent illness, abnormal laboratory finding) that emerges or worsens relative to pretreatment baseline during the treatment or post-treatment periods, regardless of the suspected cause.

For this protocol an SAE was defined as any AE that occurred at any dose if:

It resulted in death (i.e., the AE caused or led to death),
It was life threatening,
It required or prolonged inpatient hospitalization,
It was disabling,
It resulted in a congenital anomaly/birth defect,
It may have jeopardized the participant or may have required medical or surgical intervention to prevent one of the outcomes listed above.

The primary cause of death for all reported cases was disease progression, and all of the deaths occurred following study discontinuation, with one death occurring within 4 weeks of the last treatment day.

All enrolled participants

Posted

Number

participants

Days 1, 2, 5, 8, and 15 of Cycle 1; Days 1, 8, and Week 3, of Cycles 2 and beyond up to 1 year and at the follow-up visit (4 weeks after last infusion)

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	rhuMAb 2C4: 0.5 mg/kg	rhuMAb 2C4 0.5 mg/kg was administered once every 3 weeks as an IV infusion until PD or unacceptable toxicity occurred for up to a maximum of 1 year.

OG000	rhuMAb 2C4: 0.5 mg/kg	rhuMAb 2C4 0.5 mg/kg was administered once every 3 weeks as an IV infusion until PD or unacceptable toxicity occurred for up to a maximum of 1 year.
OG001	rhuMAb 2C4: 2 mg/kg	rhuMAb 2C4 2 mg/kg was administered once every 3 weeks as an IV infusion until PD or unacceptable toxicity occurred for up to a maximum of 1 year.
OG002	rhuMAb 2C4: 5 mg/kg	rhuMAb 2C4 5 mg/kg was administered once every 3 weeks as an IV infusion until PD or unacceptable toxicity occurred for up to a maximum of 1 year.
OG003	rhuMAb 2C4: 10 mg/kg	rhuMAb 2C4 10 mg/kg was administered once every 3 weeks as an IV infusion until PD or unacceptable toxicity occurred for up to a maximum of 1 year.
OG004	rhuMAb 2C4: 15 mg/kg	rhuMAb 2C4 15 mg/kg was administered once every 3 weeks as an IV infusion until PD or unacceptable toxicity occurred for up to a maximum of 1 year.