Bortezomib And Cetuximab In Treating Patients With Advanced Solid Tumors

Study Overview

Bortezomib and Cetuximab in Treating Patients With Advanced Solid Tumors

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.

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.

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

BIOLOGICAL: cetuximab
DRUG: bortezomib

CDR0000586671
UMN-2005LS037 (OTHER Identifier) (OTHER: CPRC, University of Minnesota)
MILLENNIUM-X05160 (OTHER Identifier) (OTHER: Millennium Pharm Inc.)
UMN-0506M7030372 (OTHER Identifier) (OTHER: IRB, University of Minnesota)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2008-02-22	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2017-11-29
First Submitted that Met QC Criteria 2008-02-22	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2017-12-02
First Posted (ACTUAL) 2008-02-25	Results First Posted N/A	Last Verified 2010-04

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Non Randomized

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Bortezomib and 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.	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.

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Bortezomib and 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.

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.

Primary Outcome Measures	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	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

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

PRINCIPAL_INVESTIGATOR: Arkadiusz Dudek, MD, Masonic Cancer Center, University of Minnesota

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

No publications available

Learn

Resources

Patients

Caregivers

Clinical Trial Record