Cetuximab in Treating Patients With Advanced Solid Tumors - Full Text View

Sponsored by:	University of California, Davis
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00376727

Purpose

RATIONALE: 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.

PURPOSE: This phase I trial is studying the side effects and best dose of cetuximab in treating patients with advanced solid tumors.

Condition	Intervention	Phase
Unspecified Adult Solid Tumor, Protocol Specific	Drug: cetuximab Procedure: immunologic technique Procedure: laboratory biomarker analysis Procedure: molecular diagnostic method	Phase I

MedlinePlus related topics: Cancer

Drug Information available for: Cetuximab

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	A Phase I Study of the Safety and Tolerability of Four Doses of Cetuximab (C225) in Patients With Advanced Solid Tumors

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Maximum tolerated dose of cetuximab [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Safety and tolerability of cetuximab [ Designated as safety issue: Yes ]
Potential predictors of response using correlative studies [ Designated as safety issue: No ]
Correlation of efficacy of cetuximab with grade of skin rash [ Designated as safety issue: No ]
Development of a detailed scale for assessing skin rash [ Designated as safety issue: No ]

Estimated Enrollment:	20
Study Start Date:	December 2004
Primary Completion Date:	November 2007 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

Determine the maximum tolerated dose of cetuximab in patients with advanced solid tumors.

Secondary

Evaluate the safety and tolerability of this drug in these patients.
Develop a detailed scale for assessment of rash in these patients.
Investigate potential predictors of response using correlative studies on patient tissue, buccal mucosa, and blood samples.
Obtain preliminary efficacy data and evaluate the relationship of efficacy to grade of rash.
Correlate downstream markers (e.g., pMAPK, pAKT, and Ki-67) and the presence of epidermal growth factor receptor (EGFR) polymorphisms with clinical response and/or survival.
Examine the levels of downstream marker proteins in buccal cells obtained pre- and post-treatment.
Correlate basal p27 expression levels with response and/or survival.
Determine if the presence of a K-RAS mutation influences response or survival outcome.
Correlate the presence or absence of mutant K-RAS tumor DNA shed into patient plasma with response and/or outcome.
Correlate levels of cytokines and chemokines with rash and clinical response.

OUTLINE: This is an open-label, dose-escalation study.

Patients receive cetuximab IV over 90 minutes once weekly for 4 weeks. Treatment repeats every 4 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of cetuximab until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. At least 6 patients are treated at the MTD.

Patients undergo blood and buccal mucosa collection at baseline and prior to courses 2 and 3 of treatment for molecular correlative studies. Archival tumor tissue specimens are also used for molecular correlative studies. Immunologic correlative studies are performed using patient blood samples.

After completion of study treatment, patients are followed periodically for survival.

PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study.

Eligibility

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

Criteria

DISEASE CHARACTERISTICS:

Histologically or cytologically confirmed advanced solid tumor
- Not curable by surgery, radiotherapy, or standard chemotherapy, immunotherapy or hormonal therapy
- Unknown primary tumor allowed
Epidermal growth factor receptor (EGFR)-positive tumor
Must have received ≥ 1 prior chemotherapy and/or radiotherapy regimen for metastatic disease
Measurable or evaluable disease
Asymptomatic brain metastases treated by surgical resection or radiotherapy allowed provided patient is neurologically stable and has been off steroids for ≥ 4 weeks
- No symptomatic brain metastases
Archival tumor tissue (i.e., paraffin block or ≥ 3 unstained slides) available
- Patient must be willing to submit archival tumor tissue for correlative studies

PATIENT CHARACTERISTICS:

Zubrod performance status 0-2
Life expectancy ≥ 3 months
Platelet count ≥ 100,000/mm^3
Absolute neutrophil count ≥ 1,500/mm^3
SGOT ≤ 3 times upper limit of normal
Bilirubin ≤ 2.0 mg/dL
Creatinine ≤ 1.6 mg/dL OR creatinine clearance ≥ 40 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
No uncontrolled intercurrent illness including, but not limited to, the following:
- Ongoing or active infection
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Cardiac arrhythmia
- Psychiatric illness or social situation that would preclude study treatment
No prior hypersensitivity reaction to chimerized or murine monoclonal antibody therapy

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
Recovered from prior therapy
At least 4 weeks since prior chemotherapy
At least 2 weeks since prior radiotherapy
No prior cetuximab
No other prior drug that targets the EGFR including, but not limited to, the following:
- Gefitinib
- Erlotinib hydrochloride
- CI-1033
- Trastuzumab (Herceptin)
No prior monoclonal antibody therapy
No other concurrent chemotherapy, radiotherapy, or biologic therapy
No other concurrent investigational anticancer agents
No concurrent steroids

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00376727

Locations

United States, California
University of California Davis Cancer Center
Sacramento, California, United States, 95817

Sponsors and Collaborators

University of California, Davis

Investigators

Study Chair:	Angela Davies, MD	University of California, Davis
Investigator:	Corinne Turrell, CCRP	University of California, Davis

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Study ID Numbers:	CDR0000506089, UCDCC-165, BMS-CA225027, UCDCC-200412499-3, IMCL-8420
Study First Received:	September 13, 2006
Last Updated:	July 23, 2008
ClinicalTrials.gov Identifier:	NCT00376727
Health Authority:	United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):

unspecified adult solid tumor, protocol specific

Study placed in the following topic categories:

Cetuximab

Additional relevant MeSH terms:

Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 15, 2009