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

Bristol-Myers Squibb (BMS)

Status and phase: Completed; Phase 1

Conditions: Solid Tumor; Breast Cancer

Treatments: Drug: Trastuzumab; Drug: Paclitaxel; Drug: Alvespimycin

Study type: Interventional

Funder types: Industry

Identifiers

NCT00803556

CA201-001

KDG 132

Details and patient eligibility

About

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

Enrollment: 29 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

29 participants in 2 patient groups

Arm 1

Experimental group

Description:

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

Treatment:

Drug: Alvespimycin

Drug: Trastuzumab

Arm 2

Experimental group

Description:

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

Treatment:

Drug: Alvespimycin

Drug: Paclitaxel

Drug: Trastuzumab