Clinical trial NCT00803556: 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
Official title: Phase 1 Clinical Trial of the Combination of Intravenous Alvespimycin (KOS-1022), Trastuzumab With or Without Paclitaxel
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumor
Breast Cancer
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2008-12-05
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


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

Primary outcomes:
measure: Number of Dose Limiting Toxicities
timeFrame: During Cycle 1 (4-weeks in duration)
Secondary outcomes:
measure: Summary of Adverse Events, Serious Adverse Events, Deaths and Discontinuations due to Adverse Events
timeFrame: Weekly
measure: Summary of Clinical Laboratory Abnormalities
timeFrame: Weekly
measure: AUC of KOS-1022 and its metabolites
timeFrame: 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
measure: Cmax of KOS-1022 and its metabolites
timeFrame: 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
measure: T-Half of KOS-1022 and its metabolites
timeFrame: 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
measure: Expression of Hsp90-client proteins in peripheral blood lymphocytes
timeFrame: 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
measure: Tumor response as assessed by RECIST criteria first after two cycles of therapy
timeFrame: 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)
Other outcomes:
Locations:
city: Indianapolis
country: United States
facility: Indiana University Melvin & Bren Simon Cancer Center
state: Indiana
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: