Bortezomib and Cetuximab in Treating Patients With Advanced Solid Tumors

This study has been completed.
Sponsor:
Information provided by:
Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier:
NCT00622674
First received: February 22, 2008
Last updated: April 13, 2010
Last verified: April 2010

February 22, 2008
April 13, 2010
November 2005
August 2009   (final data collection date for primary outcome measure)
Maximum tolerated dose (MTD) of bortezomib [ Time Frame: At end of Cycle 1 (Week 3) ] [ Designated as safety issue: Yes ]
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%.
Maximum tolerated dose of bortezomib when given together with cetuximab [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT00622674 on ClinicalTrials.gov Archive Site
Disease response as measured by RECIST criteria [ Time Frame: At Week 4 ] [ Designated as safety issue: No ]
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.
Disease response as measured by RECIST criteria [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Bortezomib and Cetuximab in Treating Patients With Advanced Solid Tumors
Phase I Study of Bortezomib (Velcade) and Cetuximab (Erbitux) for Patients With Solid Tumors Expressing EGFR

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.

Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Breast Cancer
  • Colorectal Cancer
  • Head and Neck Cancer
  • Kidney Cancer
  • Lung Cancer
  • Pancreatic Cancer
  • Sarcoma
  • Unspecified Adult Solid Tumor, Protocol Specific
  • 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.
    Other Name: Erbitux
  • 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.
    Other Name: Velcade
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.
Interventions:
  • Biological: cetuximab
  • Drug: bortezomib
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
37
February 2010
August 2009   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00622674
CDR0000586671, UMN-2005LS037, MILLENNIUM-X05160, UMN-0506M7030372
Yes
Arkadiusz Dudek, M.D., Masonic Cancer Center, University of Minnesota
Masonic Cancer Center, University of Minnesota
Not Provided
Principal Investigator: Arkadiusz Dudek, MD Masonic Cancer Center, University of Minnesota
Masonic Cancer Center, University of Minnesota
April 2010

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP