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A Randomized Phase II Study of Concomitant Chemoradiotherapy With 5-Fluorouracil/Hydroxyurea Compared to FHX Plus Bevacizumab for Intermediate Stage and Selected Stage IV Cancers of the Head and Neck

Phase 2
18 Years
Not Enrolling
Head and Neck Cancer

Thank you

Trial Information

A Randomized Phase II Study of Concomitant Chemoradiotherapy With 5-Fluorouracil/Hydroxyurea Compared to FHX Plus Bevacizumab for Intermediate Stage and Selected Stage IV Cancers of the Head and Neck

In this study, we intend to explore the feasibility and the effects of adding bevacizumab to
Fl-TX in patients with intermediate stage head and neck cancer and selected patients with
stage IV disease. As mentioned previously, although single modality therapy (surgery or
radiotherapy alone) is often used to treat patients with Stage II head and neck
malignancies, with substantial success, still there is a sizeable group of patients
(approximately 30% or 40%) who fail these treatments, and represent with locoregional
recurrences which are much more difficult to treat. Furthermore, the common use of radical
surgery in many instances leads to loss of organ function.

Based on this knowledge, we feel that it is justifiable to include stage II patients (T2NO)
in combined chemoradiation studies. Our extensive experience using chemoradiotherapy in
patients with regionally advanced non-metastatic Stage 4 cancers of the head and neck area
suggests that selected patients with low nodal status (Nondisease) including those with T4
primaries (i.e. T4 NO MO and T4 Nl MO) have a lower risk of distant failure than patients
that present with higher nodal status (N2 and N3 disease). Aggressive combined locoregional
therapies such as the one that will be administered in the study, are in our opinion
appropriate for this group of patients as they address the major concern which is
locoregional failure.

The primary goal of the study is exploration of the pharmacodynamic effects of bevacizumab
(10 mg/kg) on appropriate markers of angiogenesis in tumor tissue in comparison to a
non-bevacizumab containing chemoradiation regimen (FHX alone). These results will be
correlated with a number of clinical endpoints including rapidity of clinical response,
locoregional control rates, time to progression, need of salvage surgery, overall survival
and measures of QOL and organ function. The predictive and prognostic value of specific
molecular markers in patients with HNC will also be evaluated. In order to shorten the total
duration of treatment without affecting the total administered dose, we have modified our
traditional radiation schedule in FHX to include two treatment daily fractions as opposed to
one. This modification will allow for the completion of all treatment in 4 to 5 cycles as
opposed to the traditional 6 to 7 cycles. Given this modification in the radiation schedule,
we considered it prudent to include a control arm (modified FHX) in addition to B-FHX,
within a randomized design. The control arm will also help with the interpretation of the
results obtained with the measurement of the correlative markers of angiogenesis.

Inclusion Criteria:

- Patients must have stage II-III (carcinoma of head and neck, including oral cavity,
pharynx, larynx, paranasal sinuses and cervical esophagus). Selected patients with
stage disease (T will also be considered for enrolment). Therapy is given with
curative intent. Patients with clinical N2 or N3 disease are excluded.

- Prior to entry in the study the resectability and standard treatment options for each
patient will be determined during a joint evaluation by a team composed of an
attending surgeon, a radiation oncologist and a medical oncologist. In addition the
timing and feasibility of initial organ preserving surgery will be determined in each
patient prior to therapy at the discretion of the treating surgeon. Salvage surgery
and neck dissection will be allowed for suspicious or evident residual disease at the
completion of the treatment regimen.

- Measurable disease is not required.

- Patients must have a histologically or cytologically confirmed diagnosis of carcinoma
of the head and neck.

- No prior exposure to chemotherapy or radiotherapy for a malignancy of the head and

- Patients must have ECOG performance status of 0-2.

- Age 18 years of age and older.

- Patients must have normal organ and bone marrow function.

Exclusion Criteria:

- Receiving any other investigational agents

- Recent (within 6 months) myocardial infarction, New York Heart Association (NYHA) -
Class H or greater congestive heart failure, serious cardiac arrhythmia requiring
medication, or Grade II or greater peripheral vascular disease within 1 year prior to
treatment in the study

- Serious, non-healing wound, ulcer, or bone fracture.

- History of recurrent or chronic deep vein thrombosis or pulmonary embolus

- History of CNS disease (including CNS involvement from primary cancer) or hemorrhagic
or thrombotic stroke within the last 6 months

- Uncontrolled hypertension

- Evidence of bleeding diathesis or coagulopathy

- History of hemoptysis

- Anatomic lesion that increases the risk of serious hemorrhage (e.g. invasion of a
major vessel by tumor).

- History of other disease, metabolic dysfunction, physical examination finding, or
clinical laboratory finding giving reasonable suspicion of a disease or condition
that contraindicates the use of an investigational drug or that might affect the
interpretation of the results of the study or render the subject at high risk from
treatment complications.

- Current ongoing treatment with any dose of warfarin or its equivalent.

- Major surgical procedure or significant traumatic injury within 28 days prior to Day

- Fine needle aspirations, indwelling catheter placement, or significant traumatic
injury within 7 days prior to Day 0

- Anticipation of need for major surgical procedure during the course of the study.

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to rhuMAb VEUF or other agents used in the study.

- History of a concurrent malignancy or a history of a prior malignancy within the past
3 years.

- Pregnant women

- HIV-positive patients receiving combination anti-retroviral therapy

Type of Study:


Study Design:

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

Outcome Measure:

To evaluate the time to progression free survival in patients with cancer of the oral cavity, pharynx, larynx, paranasal sinuses, and cervical esophagus when treated with the concomitant chemoradiotherapy regimen

Outcome Time Frame:

From randomization until disease progression or death from any cause

Safety Issue:


Principal Investigator

Everett Vokes, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Chicago


United States: Food and Drug Administration

Study ID:




Start Date:

January 2004

Completion Date:

November 2008

Related Keywords:

  • Head and Neck Cancer
  • Head and Neck Cancer
  • Head and Neck Neoplasms



The University of ChicagoChicago, Illinois  60637