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.

Study Overview

• Status: Completed
• Conditions: Sarcoma; Kidney Cancer; Breast Cancer; Head and Neck Cancer; Colorectal Cancer; Pancreatic Cancer; Lung Cancer; Unspecified Adult Solid Tumor, Protocol Specific
• Intervention / Treatment: Biological: cetuximab; Drug: bortezomib

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.

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Masonic Cancer Center at University of Minnesota

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

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.; Other Names: 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 Names: Velcade

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Masonic Cancer Center, University of Minnesota

Study record dates

Study Major Dates

• Study Start: November 1, 2005
• Primary Completion (Actual): August 1, 2009
• Study Completion (Actual): February 1, 2010

Study Registration Dates

• First Submitted: February 22, 2008
• First Submitted That Met QC Criteria: February 22, 2008
• First Posted (Estimate): February 25, 2008

Study Record Updates

• Last Update Posted (Actual): December 2, 2017
• Last Update Submitted That Met QC Criteria: November 29, 2017
• Last Verified: April 1, 2010

More Information

Terms related to this study

• Keywords: recurrent renal cell cancer; 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 kidney cancer; recurrent sarcoma
• Additional Relevant MeSH Terms: Digestive System Diseases; Respiratory Tract Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Lung Diseases; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Pancreatic Diseases; Sarcoma; Kidney Neoplasms; Carcinoma, Renal Cell; Head and Neck Neoplasms; Lung Neoplasms; Pancreatic Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Bortezomib; Cetuximab
• Other Study ID Numbers: CDR0000586671; UMN-2005LS037 (Other Identifier: CPRC, University of Minnesota); MILLENNIUM-X05160 (Other Identifier: Millennium Pharm Inc.); UMN-0506M7030372 (Other Identifier: IRB, University of Minnesota)