Bortezomib and Cetuximab in Treating Patients With Advanced Solid Tumors

University of Minnesota (UMN)

Status and phase: Completed; Phase 1

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

Treatments: Drug: bortezomib; Biological: cetuximab

Study type: Interventional

Funder types: Other

Identifiers

NCT00622674

CDR0000586671

UMN-0506M7030372 (Other Identifier)

UMN-2005LS037 (Other Identifier)

MILLENNIUM-X05160 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 37 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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37 participants in 1 patient group

Bortezomib and Cetuximab

Experimental group

Description:

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.

Treatment:

Biological: cetuximab

Drug: bortezomib