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A Phase I Trial of Cetuximab (C225) and Pemetrexed With Concurrent Radiation in Head and Neck Cancer

Phase 1
18 Years
Not Enrolling
Head and Neck Cancer

Thank you

Trial Information

A Phase I Trial of Cetuximab (C225) and Pemetrexed With Concurrent Radiation in Head and Neck Cancer

The purpose of this Phase I study is to determine the safety and effectiveness of two
chemotherapies drugs, Cetuximab and Pemetrexed (Alimta), when given in combination with
radiation therapy. Currently Pemetrexed is approved by the Food and Drug Administration
(FDA) for two other types of cancer, mesothelioma and lung cancer, but it is considered
investigational and is not approved by the FDA for head and neck cancer. Cetuximab is
approved by the FDA for the treatment of colorectal cancer; however, it is not yet approved
for head and neck cancer.

Pemetrexed is a drug that kills tumor cells by stopping cells from functioning normally. It
has been studied in thousands of subjects and has been shown to be effective at killing
tumor cells in many cancers, including head and neck cancer. In preclinical studies,
Pemetrexed showed such promising activity against a wide range of tumor types including
those mentioned above as well as breast, colon, and bladder cancers.

Cetuximab (also known as "C225" and "Erbitux") can increase the effectiveness of our
standard treatment with chemotherapy and radiation. Cetuximab is a type of drug known as a
monoclonal antibody. Monoclonal antibodies are used to try to destroy some types of cancer
cells while causing little harm to normal cells. They are designed to recognize specific
molecules that are on the surface of particular cancer cells. The monoclonal antibody
recognizes the protein and locks onto it. This may trigger the body's immune system to
attack the cancer cells and can sometimes make the cells destroy themselves. Cetuximab
targets the epidermal growth factor receptor (EGFR), an important molecule for the growth of
cancer cells. The use of radiation therapy and Cetuximab has also been studied with good
results. We will find what effects (good and bad) Cetuximab has on you and your head and
neck cancer.

Both Cetuximab and Pemetrexed have been studied intensively to determine their

In this study, we will find what effects (good and bad) Cetuximab and Pemetrexed, with
radiation; have on you and on your head and neck cancer. We will find out if the
combination of Cetuximab, Pemetrexed and radiation has better results than what we
ordinarily expect with radiation and chemotherapy. We will also find out if the side
effects are worse than those we usually see. In addition, we will test both blood and tumor
tissue and determine what effects Cetuximab has on these specimens. Finally, we will look
for "markers," or cancer identifiers, in your tumor cells and blood that may help to predict
what the best treatment is for head and neck cancer patients in the future.

Inclusion Criteria:

- Pathologically confirmed head and neck malignancy

- All subjects requiring radiotherapy to the head and neck for a poor-prognosis
malignancy will be eligible.

- Two cohorts of subjects: no prior history of head and neck radiation, i.e.
non-irradiated and prior history of head and neck radiation, i.e. previously

- Subjects with recurrent head and neck cancer with no clinically measurable distant
disease as well as those subjects in whom distant disease was of low volume and local
and regional palliation is clinically warranted will be eligible.

- Subjects without prior treatment should have stage IV disease (see AJCC staging
system in Appendix 2, Protocol) or have an expected long-term survival of less than

- No prior treatment with systemic anti-EGFR inhibitors or Pemetrexed. Any number of
prior systemic therapies is allowed.

- Measurable or evaluable disease.

- ECOG performance status 0-2 .

- Age ³ 18 years.

- Subjects must have fully recovered from the effects of any prior surgery,
chemotherapy, or radiation therapy. A minimum time period of 4 weeks should elapse
between the completion of prior chemotherapy and enrollment in the study.

- ANC ³ 1500/µl, platelet count ³ 100,000/µl. Hemoglobin should be >8 g/dL.

- Creatinine clearance 45 ml/min or higher calculated using the Cockcroft-Gault
formula: Calculated Creatinine Clearance = (140-age) X actual body wt.(kg) 72 X serum
creatinine Multiply this number by 0.85 if the subject is female

- Total bilirubin within normal limits and AST/ALT less than 3 times the upper limit of
normal (less than 5 times the upper limit of normal in the presence of liver

- Informed consent must be obtained from all subjects prior to beginning therapy.
Subjects should have the ability to understand and the willingness to sign a written
informed consent document.

- Subjects should be willing and able to take folic acid and vitamin B12
supplementation and should interrupt aspirin or other nonsteroidal anti-inflammatory
agents for a 5-day period (8-day period for long acting agents such as piroxicam),
see section 5.57

Exclusion criteria:

- Subjects with uncontrolled intercurrent illness including, but not limited to,
ongoing or active infection or psychiatric illness/social situations that would limit
compliance with study requirements, significant history of uncontrolled cardiac
disease; i.e., uncontrolled hypertension, unstable angina, recent myocardial
infarction (within prior 3 months), uncontrolled congestive heart failure, and
cardiomyopathy with decreased ejection fraction.

- May not be receiving any other investigational agents.

- Pregnant women are excluded from this. Breastfeeding should be discontinued if the
mother is treated with chemotherapy. Prior to study enrollment, women of
childbearing potential (WOCBP) must be advised of the importance of avoiding
pregnancy during trial participation and the potential risk factors for an
unintentional pregnancy. In addition, men enrolled on this study should understand
the risks to any sexual partner of childbearing potential and should practice an
effective method of birth control. Subjects who are women of childbearing potential
and sexually active males must be willing to use effective contraception while on

- All WOCBP should be instructed to contact the Investigator immediately if they
suspect they might be pregnant .

- HIV-positive subjects are excluded from the study.

- Prior grade 3 or 4 infusion or hypersensitivity reaction to a monoclonal antibody.

- For subjects who have baseline clinically significant pleural or peritoneal effusions
before initiation of protocol therapy, consideration should be given to draining the
effusion prior to starting therapy due the potential of increased toxicity with
Pemetrexed in that setting.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

To evaluate the maximum tolerated doses and dose-limiting toxicities of Pemetrexed and Cetuximab when given concurrently with radiation in poor prognosis subjects with head and neck cancer.

Outcome Time Frame:

10 years

Safety Issue:


Principal Investigator

Julie E Bauman, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Pittsburgh


United States: Food and Drug Administration

Study ID:




Start Date:

March 2006

Completion Date:

January 2009

Related Keywords:

  • Head and Neck Cancer
  • head
  • neck
  • Cetuximab
  • Pemetrexed
  • Head and Neck Neoplasms



University of PittsburghPittsburgh, Pennsylvania  15261