Clinical trial NCT00622674: Bortezomib and Cetuximab in Treating Patients With Advanced Solid Tumors
Official title: Phase I Study of Bortezomib (Velcade) and Cetuximab (Erbitux) for Patients With Solid Tumors Expressing EGFR
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Breast Cancer
Colorectal Cancer
Head and Neck Cancer
Kidney Cancer
Lung Cancer
Pancreatic Cancer
Sarcoma
Unspecified Adult Solid Tumor, Protocol Specific
Keywords: 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
Lead sponsor: Masonic Cancer Center, University of Minnesota
Sponsor class: OTHER
First posted: 2008-02-25
Enrollment: 37
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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 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

Primary outcomes:
measure: Maximum tolerated dose (MTD) of bortezomib
timeFrame: At end of Cycle 1 (Week 3)
Secondary outcomes:
measure: Disease response as measured by RECIST criteria
timeFrame: At Week 4
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: Masonic Cancer Center at University of Minnesota
state: Minnesota
Study officials:
affiliation: Masonic Cancer Center, University of Minnesota
name: Arkadiusz Dudek, MD
role: PRINCIPAL_INVESTIGATOR
References: