Radiation, Cetuximab and Pemetrexed With or Without Bevacizumab in Locally Advanced Head and Neck Cancer

NCT00703976 | Completed Phase 2 Results DMC

• 1 other identifier: 07-021
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to compare the effects (good and bad) of chemoradiotherapy with or without Bevacizumab (Avastin). Chemoradiotherapy is the combination of chemotherapy (the drugs pemetrexed and cetuximab) and radiation. Pemetrexed is not approved by the Food and Drug Administration (FDA) for head and neck cancer when used in combination with radiation therapy. Cetuximab is also approved by the FDA for head and neck cancers in patients who have failed other chemotherapy treatments. Bevacizumab is approved by the Food and Drug Administration (FDA) for colorectal cancer and non-small cell lung cancer in combination of chemotherapy. In this study, the use of bevacizumab is investigational.

Conditions

Cancer

Keywords

head and neck cancers

Outcome Measures

Primary Outcomes (1)

• 2-year Progression-free Survival (PFS)

  Two-year PFS is an estimated percentage of participants without disease progression (locoregional or distant) at two years after the start of study treatment. Progression was defined using Response Evaluation Criteria In Solid Tumors (RECIST v1.0), as: at least a 20% (and at least 5 millimeters) increase in the sum of the diameters of target lesions, or the appearance of one or more new lesions.

  18 months to patient accrual and 2 years of follow-up after closing accrual.

Secondary Outcomes (1)

• 2-year Overall Survival (OS)

  2 years of follow-up after closing accrual

Study Arms (2)

Cetuximab, Pemetrexed and Radiation therapy

ACTIVE COMPARATOR

Cetuximab, Pemetrexed and Radiation therapy Cetuximab: Cetuximab is approved by the FDA for head and neck cancers in patients who have failed other chemotherapy treatments. Pemetrexed: Pemetrexed is approved by the Food and Drug Administration (FDA) for head and neck cancer when used in combination with radiation therapy. Radiation therapy: Radiation therapy standard fractionation 2 Gy/day without planned interruptions beginning on day 1 (Monday or Tuesday preferred). Radiation will be given 5 days/week, Monday through Friday, for 7 consecutive weeks

Drug: Cetuximab; Drug: Pemetrexed; Radiation: Radiation therapy

Cetuximab, Pemetrexed, Radiation Therapy plus Bevacizumab

EXPERIMENTAL

Cetuximab, Pemetrexed, Radiation Therapy plus Bevacizumab Cetuximab: Cetuximab is approved by the FDA for head and neck cancers in patients who have failed other chemotherapy treatments. Pemetrexed: Pemetrexed is approved by the Food and Drug Administration (FDA) for head and neck cancer when used in combination with radiation therapy. Radiation therapy: Radiation therapy standard fractionation 2 Gy/day without planned interruptions beginning on day 1 (Monday or Tuesday preferred). Radiation will be given 5 days/week, Monday through Friday, for 7 consecutive weeks Bevacizumab: Bevacizumab is approved by the Food and Drug Administration (FDA) for colorectal cancer and non-small cell lung cancer in combination of chemotherapy.

Drug: Bevacizumab; Drug: Cetuximab; Drug: Pemetrexed; Radiation: Radiation therapy

Interventions

Bevacizumab DRUG

Bevacizumab is approved by the Food and Drug Administration (FDA) for colorectal cancer and non-small cell lung cancer in combination of chemotherapy.

Also known as: Avastin

Cetuximab, Pemetrexed, Radiation Therapy plus Bevacizumab

Cetuximab DRUG

Cetuximab is approved by the FDA for head and neck cancers in patients who have failed other chemotherapy treatments.

Also known as: Erbitux

Cetuximab, Pemetrexed and Radiation therapy; Cetuximab, Pemetrexed, Radiation Therapy plus Bevacizumab

Pemetrexed DRUG

Pemetrexed is approved by the Food and Drug Administration (FDA) for head and neck cancer when used in combination with radiation therapy.

Also known as: Alimta

Cetuximab, Pemetrexed and Radiation therapy; Cetuximab, Pemetrexed, Radiation Therapy plus Bevacizumab

Radiation therapy RADIATION

Radiation therapy standard fractionation 2 Gy/day without planned interruptions beginning on day 1 (Monday or Tuesday preferred). Radiation will be given 5 days/week, Monday through Friday, for 7 consecutive weeks

Cetuximab, Pemetrexed and Radiation therapy; Cetuximab, Pemetrexed, Radiation Therapy plus Bevacizumab

Eligibility Criteria

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

You may qualify if:

• All patients must have pathologically confirmed AJCC 6th edition (see Appendix) stage III or IV (M0) squamous cell carcinoma or undifferentiated or poorly differentiated carcinoma of the oropharynx, larynx, or hypopharynx with no evidence of distant metastasis. Biopsy sampling of primary tumor with pathology report documentation of confirmed diagnostic tissue type is required. Patients should be evaluated by a Radiation Oncologist, Medical Oncologist and Otolaryngologist prior to enrolling on study.
• No prior treatment for head and neck cancer. Limited, organ-preserving surgery is allowed
• ECOG performance status 0-1
• Unidimensionally measurable disease is not required. However, patients should require treatment with full dose radiotherapy (not postoperative)
• Age greater or equal to 18 years
• Absolute neutrophil count greater or equal to 1500/µl, Platelet count greater or equal to 100,000/µl
• Creatinine clearance 45 ml/min or higher calculated using the Cockcroft-Gault formula
• Total bilirubin within normal limits and AST/ALT less than 3 times the upper limit of normal
• Urine protein should be screened by urine analysis for Urine Protein Creatinine (UPC) ratio. For UPC ratio \>0.5, 24-hour urine protein should be obtained and the level must be \<1000mg for patients to be eligible
• Informed consent must be obtained from all patients prior to beginning therapy. Patients should have the ability to understand and the willingness to sign a written informed consent document
• Patients should be willing and able to take folic acid and vitamin B12 supplementation and should interrupt aspirin or other non-steroidal anti-inflammatory agents for a 5-day period
• The use of anti-platelet agents(e.g. dipyridamole (Persatine), ticlopidine (Ticlid), clopidogrel (Plavix)) is allowed only if patient is not receiving aspirin or NSAID's known to inhibit platelet function.
• Patients who meet the following criteria will be excluded due to the possibility of increased risk for tumor bleeding with bevacizumab therapy:
• active bleeding due to head and neck cancer of more than ½ teaspoon of bright red blood per episode or history of persistent bleeding due to SCCHN that required major intervention (surgery or embolization) to be controlled.
• history of gross hemoptysis (bright red blood of .05 teaspoon or more per episode of coughing) less than or equal to 3 months prior to enrollment

You may not qualify if:

• Patients who are receiving any other investigational agents.
• Ineligible will be patients 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.
• Patients should not have prior history of a serious reaction to a monoclonal antibody. Patients with known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies are not eligible.
• Women must not be pregnant or breast feeding because chemotherapy may be harmful to the fetus or the nursing infant. Pregnant women are excluded from this study because chemotherapy and/or bevacizumab have the potential for teratogenic or abortifacient effects.
• HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible drug interactions with study drugs. Appropriate studies will be undertaken in patients receiving combination anti-retroviral therapy when indicated.

Sponsors & Collaborators

• University of Pittsburgh: lead
• Eli Lilly and Company: collaborator
• Genentech, Inc.: collaborator

Study Sites (1)

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15232, United States

Location

MeSH Terms

Conditions

Neoplasms; Head and Neck Neoplasms

Interventions

Bevacizumab; Cetuximab; Pemetrexed; Radiotherapy

Condition Hierarchy (Ancestors)

Neoplasms by Site

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

Results Point of Contact

• Title: Julie Bauman, MD
• Organization: University of Pittsburgh

baumanje@upmc.edu

412-623-7833

Study Officials

• Julie E Bauman, MD

  University of Pittsburgh Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 20, 2008
• First Posted: June 24, 2008
• Study Start: October 1, 2008
• Primary Completion: September 1, 2014
• Study Completion: September 1, 2014
• Last Updated: April 4, 2017
• Results First Posted: April 4, 2017

Record last verified: 2017-02

Locations

US (1)