Bortezomib and Cetuximab in Treating Patients With Advanced Solid Tumors
- Conditions
- Lung CancerBreast CancerColorectal CancerHead and Neck CancerKidney CancerPancreatic CancerSarcomaUnspecified Adult Solid Tumor, Protocol Specific
- Interventions
- Biological: cetuximab
- Registration Number
- NCT00622674
- Lead Sponsor
- Masonic Cancer Center, University of Minnesota
- Brief Summary
RATIONALE: Bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving bortezomib together with cetuximab may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of bortezomib when given together with cetuximab in treating patients with advanced solid tumors.
- Detailed Description
OBJECTIVES:
Primary
* To determine the maximum tolerated dose of bortezomib when given together with cetuximab in patients with advanced solid tumors expressing epidermal growth factor receptor (EGFR).
Secondary
* To obtain preliminary information about the anti-tumor activity of bortezomib and cetuximab.
OUTLINE: This is a dose-escalation study of bortezomib.
Patients receive bortezomib intravenously (IV) on days 1 and 8 and cetuximab IV over 60-90 minutes on days 1, 8, and 15. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
After the maximum tolerated dose (MTD) is determined, an additional 10 patients are treated at the MTD.
After completion of study treatment, patients are followed periodically for up to 1 year.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 37
-
Diagnosis of solid tumor that overexpresses epidermal growth factor receptor (EGFR) including, but not limited to, the following:
- Breast cancer
- Lung cancer
- Colon cancer
- Pancreatic cancer
- Head and neck cancer
- Kidney cancer
- Sarcoma
-
Advanced disease
- Must have failed or become intolerant to prior standard therapy and is no longer likely to respond to such therapy
-
Measurable or nonmeasurable disease
-
ECOG performance status 0-1
-
ANC ≥ 1,500/mm³
-
Platelet count > 100,000/mm³
-
Hemoglobin > 9 g/dL
-
Bilirubin < 1.5 times upper limit of normal (ULN)
-
Alkaline phosphatase < 3.0 times ULN (5.0 times ULN if liver has tumor involvement)
-
Aspartate aminotransferase (AST) and alanine aminotransferase (*ALT) < 3.0 times upper limit of normal (ULN) (5.0 times ULN if liver has tumor involvement)
-
Creatinine clearance > 30 mL/min
-
Not pregnant or nursing
-
Negative pregnancy test
-
Fertile patients must use effective contraception during and for 3 months after completion of study treatment
-
Recovered from all prior therapy
-
Prior systemic chemotherapy, immunotherapy, or biological therapy allowed
-
At least 14 days since prior radiotherapy or systemic therapy
-
At least 30 days since prior investigational agents
-
At least 14 days since other prior investigational drugs (for reasons other than the treatment of cancer)
- Untreated or symptomatic central nervous system (CNS) metastases
- Concurrent serious systemic disorders (e.g., active infection) that, in the opinion of the investigator, would compromise the safety of the patient or compromise the patient's ability to complete the study
- Uncontrolled diabetes
- Myocardial infarction within the past 6 months
- New York Heart Association (NYHA) class III or IV heart failure
- Uncontrolled angina
- Severe uncontrolled ventricular arrhythmias
- Evidence of acute ischemia or active conduction system abnormalities by ECG
- Peripheral neuropathy Common Terminology Criteria for Adverse Events (CTCAE) grade > 2
- Known hypersensitivity to bortezomib, boron, or mannitol
- Serious medical or psychiatric illness likely to interfere with study participation
- Prior bortezomib and/or cetuximab
- Concurrent filgrastim (G-CSF) or other hematologic support during course 1 of study treatment
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Bortezomib and Cetuximab cetuximab The starting dose of bortezomib will be 1.3 mg/m2 with a 0.1 increment increase with each successive dose level to a maximum of 2.0 mg/m2. A loading dose of cetuximab will be given on day 1 (400 mg/m2) followed by a weekly dose of 250 mg/m2. Bortezomib and Cetuximab bortezomib The starting dose of bortezomib will be 1.3 mg/m2 with a 0.1 increment increase with each successive dose level to a maximum of 2.0 mg/m2. A loading dose of cetuximab will be given on day 1 (400 mg/m2) followed by a weekly dose of 250 mg/m2.
- Primary Outcome Measures
Name Time Method Maximum tolerated dose (MTD) of bortezomib At end of Cycle 1 (Week 3) The standard Phase I design will be used to determine the maximum tolerated dose of bortezomib when given with weekly cetuximab. The MTD is defined as the highest dose studied for which the incidence of dose limiting toxicity (DLT) was less than 33%.
- Secondary Outcome Measures
Name Time Method Disease response as measured by RECIST criteria At Week 4 The best overall response is the best response recorded from registration until disease progression/recurrence, taking as reference for progressive disease the smallest measurements recorded since registration.
Trial Locations
- Locations (1)
Masonic Cancer Center at University of Minnesota
🇺🇸Minneapolis, Minnesota, United States