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A Phase I Study of the Safety and Tolerability of Four Doses of Cetuximab (C225) in Patients With Advanced Solid Tumors

Phase 1
18 Years
Not Enrolling
Unspecified Adult Solid Tumor, Protocol Specific

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Trial Information

A Phase I Study of the Safety and Tolerability of Four Doses of Cetuximab (C225) in Patients With Advanced Solid Tumors



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


- 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

- 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

- Examine the levels of downstream marker proteins in buccal cells obtained pre- and

- 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

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.

Inclusion Criteria:

- Signed written informed consent

- Histologically or cytologically proven advanced solid tumors not curable by surgery,
radiation therapy or standard chemo-, immuno-, or hormonal therapy. A specific
primary cancer need not have been identified (i.e., unknown primary is eligible).

- Patients must have received at least one prior regimen (chemotherapy and/or
radiation) for metastatic disease. There is no limit to the number of prior

- Any prior chemotherapy must have been completed at least 4 weeks prior to start of
study therapy. Previous radiation therapy must have been completed at least 2 weeks
prior to start of study therapy. All side effects of prior therapy must be resolved
prior to the start of study therapy.

- Patients with ZUBROD performance status 0-2 (see Appendix 1).

- Patients must have measurable disease or evaluable disease.

- Patients must have an estimated survival of at least 3 months.

- Patients with asymptomatic treated brain metastasis (surgical resection or
radiotherapy) may be included if they are neurologically stable and have been off
steroids for at least 4 weeks.

- Patients >/= 18 years of age.

- Patients of reproductive potential must agree to use an effective contraceptive
method while on treatment and for 3 months afterward as the effects of cetuximab on
the unborn fetus are unknown.

- Patients must have adequate hematologic function defined as: ANC >/= 1,500/mm3,
platelets >/= 100,000/mm3.

- Patients must have adequate hepatic function defined as SGOT UNL and serum bilirubin
- Patients must have adequate renal function defined as a serum creatinine level 1.6 mg/dL or a calculated creatinine clearance of >/= 40 ml/min.

Exclusion Criteria:

- Female patients cannot be pregnant or breastfeeding as the effects of cetuximab on
the unborn fetus are unknown. Documentation of a negative pregnancy test prior to
treatment is required for all women of reproductive potential.

- Uncontrolled intercurrent illness including but not limited to ongoing infection or
active infection, symptomatic congestive heart failure, unstable angina pectoris,
cardiac arrhythmia, or psychiatric illness/social situation that would limit
compliance with study requirements.

- Patients with symptomatic brain metastasis or still requiring steroids.

- Patients who have received prior cetuximab therapy, prior therapy with any other drug
that targets the EGF receptor (including, but not limited to, Iressa, Tarceva,
Herceptin, CI1033, etc.), or prior therapy with a monoclonal antibody.

- Patients who have received prior chemotherapy within 4 weeks or radiation therapy
within 2 weeks prior to the start of study therapy.

- Prior hypersensitivity reaction to chimerized or murine monoclonal antibody therapy.

- Patients may not receive any other chemotherapy, radiation therapy, or biologic
therapy while on study.

Type of Study:


Study Design:

Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated dose of cetuximab

Outcome Time Frame:

December 2007

Safety Issue:


Principal Investigator

Angela Davies, MD

Investigator Role:

Study Chair

Investigator Affiliation:

University of California, Davis


United States: Food and Drug Administration

Study ID:




Start Date:

December 2004

Completion Date:

December 2007

Related Keywords:

  • Unspecified Adult Solid Tumor, Protocol Specific
  • unspecified adult solid tumor, protocol specific
  • Neoplasms



University of California Davis Cancer Center Sacramento, California  95817