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

Breast Cancer Clinical Trial

Official title:

Phase 1 Clinical Trial of the Combination of Intravenous Alvespimycin (KOS-1022), Trastuzumab With or Without Paclitaxel

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00803556
• Other study ID #: CA201-001
• Secondary ID: KDG 132
• Status: Completed
• Phase: Phase 1
• First received: December 4, 2008
• Last updated: June 23, 2011
• Start date: January 2006
• Est. completion date: August 2009

Study information

• Verified date: June 2011
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 29
• Est. completion date: August 2009
• Est. primary completion date: August 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Solid Tumor

Intervention

Drug:
• Alvespimycin
Solution, IV, 60-100 mg/m2, weekly until disease progression or DLT
• Trastuzumab
Solution, IV, 2-4 mg/kg, weekly until disease progression or DLT
• Paclitaxel
Solution, IV, 60-90 mg/m2, weekly until disease progression or DLT

Locations

Country	Name	City	State
United States	Indiana University Melvin & Bren Simon Cancer Center	Indianapolis	Indiana
United States	Memorial Sloan Kettering Cancer Center	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Dose Limiting Toxicities		During Cycle 1 (4-weeks in duration)	Yes
Secondary	Summary of Adverse Events, Serious Adverse Events, Deaths and Discontinuations due to Adverse Events		Weekly	Yes
Secondary	Summary of Clinical Laboratory Abnormalities		Weekly	Yes
Secondary	AUC of KOS-1022 and its metabolites		Week 1 and Week 4: pretreatment, 30 and 55 minutes after start of infusion, 5, 15, 30 minutes and 1, 2, 4, 6, 24, 72 hours post-infusion; Weeks 2 and 3: pre-infusion	No
Secondary	Cmax of KOS-1022 and its metabolites		Week 1 and Week 4: pretreatment, 30 and 55 minutes after start of infusion, 5, 15, 30 minutes and 1, 2, 4, 6, 24, 72 hours post-infusion; Weeks 2 and 3: pre-infusion	No
Secondary	T-Half of KOS-1022 and its metabolites		Week 1 and Week 4: pretreatment, 30 and 55 minutes after start of infusion, 5, 15, 30 minutes and 1, 2, 4, 6, 24, 72 hours post-infusion; Weeks 2 and 3: pre-infusion	No
Secondary	Expression of Hsp90-client proteins in peripheral blood lymphocytes		Pretreatment, 4 hours following the Day 1 KOS-1022 infusion, Day 2, Day 4; pretreatment samples Weeks 2 and 3; pretreatment, 4 hours following the Day 22 KOS-1022 infusion, Day 23, Day 25	No
Secondary	Tumor response as assessed by RECIST criteria first after two cycles of therapy		For patients with measurable disease, response will be assessed by RECIST criteria first after two cycles of therapy (8 weeks in patients having no delay in the schedule of administration)	No

External Links

•   BMS Clinical Trials Disclosure
•   For FDA Safety Alerts and Recalls refer to the following link: http://www.fda.gov/MEDWATCH/safety.htm
•   Investigator Inquiry form