Clinical Trial of the Combination of Intravenous Alvespimycin (KOS-1022), Trastuzumab With or Without Paclitaxel in Patients With Advanced Solid Tumor Malignancies or Her2 Positive Metastatic Breast Cancer Who Have Previously Failed Trastuzumab Therapy

NCT ID: NCT00803556

Last Updated: 2011-06-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 29 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-01-31
• Study Completion Date: 2009-08-31

Brief Summary

To determine the Maximally Tolerable Dose (MTD) of KOS-1022 when administered weekly in combination with trastuzumab or in combination with trastuzumab and paclitaxel to patients with advanced solid tumor malignancies

Conditions

Solid Tumor; Breast Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm 1

Patients whose last dose is > 21 days prior to first dose of Trastuzumab on study. First infusion: 90 mins for 4 mg/kg loading dose of trastuzumab followed by 60 min infusion of alvespimycin. Subsequent infusions weekly 30 mins for 2 mg/kg trastuzumab followed by 60 min infusion of alvespimycin

Patients whose last dose is < 21 days prior to first dose of Trastuzumab on study. All infusions: 30 mins for 2 mg/kg trastuzumab followed by 60 min infusion of alvespimycin

Group Type: EXPERIMENTAL

Alvespimycin

Intervention Type: DRUG

Solution, IV, 60-100 mg/m2, weekly until disease progression or DLT

Trastuzumab

Intervention Type: DRUG

Solution, IV, 2-4 mg/kg, weekly until disease progression or DLT

Arm 2

Patients whose last dose is > 21 days prior to first dose of Trastuzumab on study. First infusion: 90 mins for 4 mg/kg loading dose of trastuzumab followed by 60 min infusion of paclitaxel and 60 min of infusion of alvespimycin. Subsequent infusions weekly 30 mins for 2 mg/kg trastuzumab followed by 60 min infusion of paclitaxel and 60 min infusion of alvespimycin

Patients whose last dose is < 21 days prior to first dose of Trastuzumab on study. All infusions: 30 mins for 2 mg/kg trastuzumab followed by 60 min infusion of paclitaxel and 60 min infusion of alvespimycin. Subsequent infusions weekly 30 mins for 2 mg/kg trastuzumab followed by 60 min infusion of paclitaxel and 60 min infusion of alvespimycin

Group Type: EXPERIMENTAL

Alvespimycin

Intervention Type: DRUG

Solution, IV, 60-100 mg/m2, weekly until disease progression or DLT

Trastuzumab

Intervention Type: DRUG

Solution, IV, 2-4 mg/kg, weekly until disease progression or DLT

Paclitaxel

Intervention Type: DRUG

Solution, IV, 60-90 mg/m2, weekly until disease progression or DLT

Interventions

Alvespimycin

Solution, IV, 60-100 mg/m2, weekly until disease progression or DLT

Intervention Type: DRUG

Trastuzumab

Solution, IV, 2-4 mg/kg, weekly until disease progression or DLT

Intervention Type: DRUG

Paclitaxel

Solution, IV, 60-90 mg/m2, weekly until disease progression or DLT

Intervention Type: DRUG

Other Intervention Names

BMS-826476; Herceptin; BMS-722782; Taxol; BMS-181339

Eligibility Criteria

Inclusion Criteria

• KPS performance status >= 70%
• Schedule A: all patients must have a histologically confirmed solid tumor malignancy. Schedule B: patients must have metastatic breast cancer with Her2 amplification by FISH or 3+ Her2 overexpression by immunohistochemistry ("IHC"). Patients are not required to have measurable disease for this investigation. Disease must be assessed within 28 days prior to treatment initiation
• All Adverse Events of any prior chemotherapy, surgery, or radiotherapy, must have resolved to NCI CTCAE (v. 3.0) Grade <= 2 (except for alopecia)
• The following laboratory results, within 10 days of KOS-1022 administration:

• Hemoglobin >= 8.5 g/dL
• Absolute neutrophils count >= 1.5 x 10*9* /L
• Platelet count >= 75 x 10*9*/L
• Serum bilirubin <= 2 x ULN
• AST and ALT <= 2.5 x ULN
• Serum creatinine <= 2 x ULN

Exclusion Criteria

• Documented hypersensitivity reaction of CTCAE Grade >= 3 to prior therapy containing trastuzumab
• Pregnant or breast-feeding women. Male patients must be surgically sterile or agree to use an acceptable method of contraception
• Known active CNS metastases
• Administration of any other chemotherapy, biological, immunotherapy or investigational agent (therapeutic or diagnostic) within 14 days prior to receipt of study medication. Patients should be 6 weeks from last dose of nitrosourea
• Patients with Grade 2 or higher dyspnea at rest on room air; patients with other clinically significant pulmonary co-morbidity(s) that might predispose the patient to pulmonary toxicity
• Moderately severe dry eye
• Prior pulmonary toxic chemotherapy (e.g, bleomycin or carmustine)
• Congestive heart failure, or a left ventricular ejection fraction (LVEF)
• Any medical conditions that, in the Investigator's opinion, would impose excessive risk to the patient
• Patients with previous malignancies unless free of recurrence for at least 5 years except cured basal cell carcinoma of the skin, carcinoma-in-situ of either the uterine cervix or urinary bladder

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: lead

Responsible Party

Bristol-Myers Squibb

Principal Investigators

Bristol-Myers Squibb

Role: STUDY_DIRECTOR

Bristol-Myers Squibb

Locations

Indiana University Melvin & Bren Simon Cancer Center

Indianapolis, Indiana, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Countries

United States

Related Links

http://www.bms.com/clinical_trials/Pages/Investigator_Inquiry_form.aspx

Investigator Inquiry form

Other Identifiers

KDG 132

Identifier Type: -

Identifier Source: secondary_id

CA201-001

Identifier Type: -

Identifier Source: org_study_id