Trial of Cetuximab and Pemetrexed With Radiation in Head and Neck Cancer

NCT00291707 | Completed Phase 1 DMC

• 1 other identifier: 05-005
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Head and Neck Cancer

Keywords

head; neck; Cetuximab; Pemetrexed

Outcome Measures

Primary Outcomes (1)

• 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.

  10 years

Secondary Outcomes (2)

• To evaluate the objective response rate post chemoradiotherapy (in subjects with measurable disease), time to progression, and overall survival with the above therapy.

  10 years

• To collect tumor tissue from pretreatment biopsies for future biomarker studies and to collect pre- and post-therapy blood samples for future studies, that may include analysis of DNA and RNA extracted from these samples.

  indefinite

Interventions

Cetuximab DRUG

The initial dose of cetuximab is 400 mg/m2 intravenously administered over 120 minutes, followed by weekly infusions at 250 mg/m2 IV over 60 minutes. The infusion rate of cetuximab must never exceed 5 mL/min.

Also known as: C225, ERBITUX

Pemetrexed DRUG

• Pemetrexed 350-500 mg/m2 IV over 10 minutes (see dose escalation design. Dose will be decreased to 200 mg/m2, if the first dose level of 350 mg/m2 is not tolerable) on days 1 and 22, (and 43 if \>6000 cGy to be delivered)

Also known as: ALIMTA

radiation therapy PROCEDURE

• Radiation therapy standard fractionation 2 Gy/day without planned interruptions beginning on day 1. Radiation will be given M-F for 6-7 consecutives weeks

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 irradiated.
• 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 10%.
• 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 metastases).
• 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

You may not qualify if:

• 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 study.
• 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.

Sponsors & Collaborators

• University of Pittsburgh: lead
• Eli Lilly and Company: collaborator
• Bristol-Myers Squibb: collaborator

Study Sites (1)

University of Pittsburgh

Pittsburgh, Pennsylvania, 15232, United States

Location

MeSH Terms

Conditions

Head and Neck Neoplasms

Interventions

Cetuximab; Pemetrexed; Radiotherapy

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic; Therapeutics

Study Officials

• Julie E Bauman, MD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 10, 2006
• First Posted: February 14, 2006
• Study Start: March 1, 2006
• Primary Completion: March 1, 2008
• Study Completion: January 1, 2009
• Last Updated: May 6, 2013

Record last verified: 2013-05

Locations

US (1)