Bortezomib and Cetuximab in Treating Patients With Advanced Solid Tumors

Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00622674
• Other study ID #: CDR0000586671
• Secondary ID: UMN-2005LS037MIL
• Status: Completed
• Phase: Phase 1
• First received: February 22, 2008
• Last updated: November 29, 2017
• Start date: November 2005
• Est. completion date: February 2010

Study information

• Verified date: April 2010
• Source: Masonic Cancer Center, University of Minnesota
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 37
• Est. completion date: February 2010
• Est. primary completion date: August 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Carcinoma, Renal Cell
• Colorectal Cancer
• Colorectal Neoplasms
• Head and Neck Cancer
• Head and Neck Neoplasms
• Kidney Cancer
• Kidney Neoplasms
• Lung Cancer
• Lung Neoplasms
• Pancreatic Cancer
• Pancreatic Neoplasms
• Sarcoma
• Unspecified Adult Solid Tumor, Protocol Specific

Intervention

Biological:
• cetuximab
A loading dose of cetuximab will be given on day 1 (400 mg/m2) followed by a weekly dose of 250 mg/m2.

Drug:
• 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.

Locations

Country	Name	City	State
United States	Masonic Cancer Center at University of Minnesota	Minneapolis	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Masonic Cancer Center, University of Minnesota

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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