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
  Purpose

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.


Condition Intervention Phase
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
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Study of Bortezomib (Velcade) and Cetuximab (Erbitux) for Patients With Solid Tumors Expressing EGFR

Resource links provided by NLM:


Further study details as provided by Masonic Cancer Center, University of Minnesota:

Primary Outcome Measures:
  • 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%.


Secondary Outcome Measures:
  • 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.


Enrollment: 37
Study Start Date: November 2005
Study Completion Date: February 2010
Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00622674

Locations
United States, Minnesota
Masonic Cancer Center at University of Minnesota
Minneapolis, Minnesota, United States, 55455
Sponsors and Collaborators
Masonic Cancer Center, University of Minnesota
Investigators
Principal Investigator: Arkadiusz Dudek, MD Masonic Cancer Center, University of Minnesota
  More Information

Additional Information:
No publications provided

Responsible Party: Arkadiusz Dudek, M.D., Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier: NCT00622674     History of Changes
Other Study ID Numbers: CDR0000586671, UMN-2005LS037, MILLENNIUM-X05160, UMN-0506M7030372
Study First Received: February 22, 2008
Last Updated: April 13, 2010
Health Authority: United States: Food and Drug Administration

Keywords provided by Masonic Cancer Center, University of Minnesota:
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

Additional relevant MeSH terms:
Breast Neoplasms
Carcinoma, Renal Cell
Kidney Neoplasms
Colorectal Neoplasms
Head and Neck Neoplasms
Lung Neoplasms
Pancreatic Neoplasms
Neoplasms
Sarcoma
Neoplasms by Site
Breast Diseases
Skin Diseases
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Urologic Neoplasms
Urogenital Neoplasms
Kidney Diseases
Urologic Diseases
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms

ClinicalTrials.gov processed this record on April 15, 2014