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Randomized Phase II Feasibility Study of Cetuximab Combined With 4 Cycles of TPF Followed by Platinum Based Chemo-radiation Strategies


Phase 2
18 Years
75 Years
Not Enrolling
Both
Head and Neck Cancer

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Trial Information

Randomized Phase II Feasibility Study of Cetuximab Combined With 4 Cycles of TPF Followed by Platinum Based Chemo-radiation Strategies


OBJECTIVES:

- To determine the safety profile of chemoradiotherapy with carboplatin vs cisplatin in
patients with newly diagnosed, unresectable stage III or IV squamous cell carcinoma of
the head and neck.

- To select one of these chemoradiotherapy regimens to be used as an experimental arm in
a future phase III trial.

- To look for EGFR expression and downstream signaling in reacting skin samples from
patients experiencing skin toxicity and in normal skin samples from the same patients
for comparison with skin samples from patients who have not shown skin toxicity.

- To explore which factors related to EGFR predict the biological activity of cetuximab
in patients treated with these regimens.

OUTLINE: This is a multicenter study.

Patients receive induction chemotherapy comprising docetaxel IV over 1 hour and cisplatin IV
over 1 hour on day 1 and fluorouracil IV continuously over 24 hours on days 1-5. Treatment
repeats every 3 weeks for up to 4 courses in the absence of unacceptable toxicity.

Within 3 weeks after completion of induction chemotherapy or within 5 weeks from the start
of the last chemotherapy course (day 21), patients are stratified by institution and
treatment response (stable disease [SD], partial response [PR], or complete response [CR] vs
non-response [progressive disease]). Patients with progressive disease are removed from
study and patients with SD, PR, or CR are randomized to 1 of 2 treatment arms.

- Arm I: Patients undergo radiotherapy (RT) (3-dimensional conformal RT or
intensity-modulated RT) on days 1-5 weekly for up to 7 weeks. Beginning on day 1 of RT,
patients receive cisplatin IV over 1 hour once weekly for up to 7 weeks.

- Arm II: Patients undergo RT as in arm I. Beginning on day 1 of RT, patients receive
carboplatin IV over 1 hour once weekly for up to 7 weeks.

Patients in both arms receive cetuximab IV over 1-2 hours once weekly beginning on day 1 of
induction chemotherapy and continuing until the end of concurrent chemoradiotherapy.

Primary tumor tissue and skin biopsies, including fixed paraffin-embedded tissue specimens
or frozen tissue, are collected at baseline (prior to treatment) and after completion of
study treatment for correlative laboratory studies of EGFR expression and downstream
signaling. Specimens are assessed by immunohistochemistry, fluorescence in situ
hybridization, and reverse transcriptase-PCR sequencing of genes and proteins for
ErbB-related activation. In the event of skin toxicity during treatment, patients undergo at
least two additional biopsies, one in reacting skin and one in normal skin. Samples are
assessed for markers of treatment efficacy related to cetuximab.

After completion of study therapy, patients are followed at 3 months and periodically
thereafter.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Histologically confirmed newly diagnosed squamous cell carcinoma of the head and neck

- Stage III or IV disease

- Unresectable disease

- Unidimensionally or bidimensionally measurable disease

- Skin and tumor material must be available for EGFR status and downstream signaling
studies

- No nasopharyngeal, nasal, or paranasal cancer

- No distant metastases

PATIENT CHARACTERISTICS:

- WHO performance status 0-1

- Absolute neutrophil count ≥ 1,500/mm³

- Platelet count ≥ 100,000/mm³

- Bilirubin ≤ 1.5 times the upper limit of normal (ULN)

- Alkaline phosphatase and transaminases ≤ 2.5 times ULN

- Serum creatinine ≤ 120 μmol/L (1.36 mg/dL)

- Creatinine clearance ≥ 60 mL/min

- Normal cardiac function (i.e., LVEF ≥ 50%)

- Clinically satisfactory 12-lead ECG

- No serious cardiac illness or medical condition within the past 6 months

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No current malignancies at other sites with the exception of cone-biopsied carcinoma
of the cervix and adequately treated basal or squamous cell skin carcinoma or other
cancer from which the patient has been disease-free for at least the past five years

- No unstable systemic diseases

- No active uncontrolled infections

- No psychological, familial, sociological, or geographical condition that would
preclude compliance with the study protocol and follow-up schedule

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- No prior treatment for head and neck cancer

- No other concurrent anticancer therapy

- No other concurrent investigational agents

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Feasibility of the chemoradiotherapy part of the treatment, assessed as at least 80% dose intensity of any of the radiotherapy, the platinum, and cetuximab during the chemoradiotherapy part of the treatment

Safety Issue:

No

Principal Investigator

Jan B. Vermorken, MD, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Universitair Ziekenhuis Antwerpen

Authority:

United States: Federal Government

Study ID:

EORTC-24061

NCT ID:

NCT00646659

Start Date:

February 2008

Completion Date:

April 2011

Related Keywords:

  • Head and Neck Cancer
  • stage III squamous cell carcinoma of the hypopharynx
  • stage III squamous cell carcinoma of the larynx
  • stage III squamous cell carcinoma of the lip and oral cavity
  • stage III squamous cell carcinoma of the oropharynx
  • stage IV squamous cell carcinoma of the hypopharynx
  • stage IV squamous cell carcinoma of the larynx
  • stage IV squamous cell carcinoma of the lip and oral cavity
  • stage IV squamous cell carcinoma of the oropharynx
  • untreated metastatic squamous neck cancer with occult primary
  • Head and Neck Neoplasms

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