Bortezomib and Cetuximab in Treating Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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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
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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.

Official Title
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Phase I Study of Bortezomib (Velcade) and Cetuximab (Erbitux) for Patients With Solid Tumors Expressing EGFR

Conditions
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Breast Cancer, Colorectal Cancer, Head and Neck Cancer, Kidney Cancer, Lung Cancer, Pancreatic Cancer, Sarcoma, Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
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* Biological: cetuximab
* Drug: bortezomib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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) Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bortezomib and Cetuximab<br>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. | Biological: cetuximab<br>* A loading dose of cetuximab will be given on day 1 (400 mg/m2) followed by a weekly dose of 250 mg/m2.<br>* Other names: Erbitux;Drug: bortezomib<br>* 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.<br>* Other names: Velcade;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose (MTD) of bortezomib | 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%. | At end of Cycle 1 (Week 3) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease response as measured by RECIST criteria | 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. | At Week 4 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent breast cancer, recurrent non-small cell lung cancer, recurrent small cell lung cancer, recurrent colon cancer, recurrent pancreatic cancer, recurrent head and neck cancer, recurrent sarcoma, recurrent kidney cancer, recurrent renal cell cancer