Clinical trial NCT00665392: Cetuximab and Combination Chemotherapy in Patients With Stage III-IV Resectable Oropharynx Cancer
Official title: Induction Chemotherapy With Cetuximab, Docetaxel, Cisplatin, and Fluorouracil (ETPF) in Patient With Resectable Stage III-IV Squamous Cell Carcinoma of the Oropharynx
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Head and Neck Cancer
Keywords: stage III squamous cell carcinoma of the oropharynx
stage IV squamous cell carcinoma of the oropharynx
tongue cancer
Lead sponsor: GERCOR - Multidisciplinary Oncology Cooperative Group
Sponsor class: OTHER
First posted: 2008-04-23
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Drugs used in chemotherapy, such as docetaxel, cisplatin, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) together with cetuximab may kill more tumor cells.

PURPOSE: This phase II clinical trial is studying how well cetuximab given together with combination chemotherapy works in treating patients with stage III or stage IV oropharynx cancer that can be removed by surgery.

Detailed description: OBJECTIVES:

Primary

* To determine the complete clinical response rate at 3 months in patients with stage III or IV nonmetastatic squamous cell carcinoma of the oropharynx treated with cetuximab, docetaxel, cisplatin, and fluorouracil.

Secondary

* To determine the rate of tumor response.
* To determine progression-free and overall survival.
* To determine the rate of complete pathological response.
* To assess the tolerability of this regimen in these patients.

OUTLINE: This is a multicenter study.

Patients receive cetuximab IV over 1-2 hours on days 1, 8, and 15; docetaxel IV over 1 hour and cisplatin IV over 1 hour on day 1; and fluorouracil IV continuously on days 1-5. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed every 2 months for 1 year and every 3 months for 2 years.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed squamous cell carcinoma of the oropharynx

  * Stage III (T3 or T1-2, N1-2, M0) or nonmetastatic stage IV (T4 or T1-3, N3, M0) disease
  * Resectable disease
* Measurable or evaluable disease
* Tumor tissue available

PATIENT CHARACTERISTICS:

Inclusion criteria:

* WHO performance status 0-1
* ANC ≥ 1,500/mm3
* Platelet count ≥ 100,000/mm3
* Hemoglobin ≥ 9 g/dL
* Creatinine \< 1.5 times upper limit of normal (ULN)
* Creatinine clearance ≥ 60 mL/min
* AST and ALT \< 5 times ULN
* Bilirubin \< 1.5 times ULN
* Not pregnant or nursing
* Fertile patients must use effective contraception
* Affiliated with social security (including CMU)

Exclusion criteria:

* Cardiovascular accident (myocardial infarction, cerebral vascular accident) within the past 6 months
* Serious and/or uncontrolled cardiac or respiratory disease (pulmonary fibrosis, interstitial pneumopathy)
* Other cancer within the past 5 years except for resected skin cancer, localized cutaneous or totally resected melanoma, or resected carcinoma in situ of the cervix
* Auditory condition precluding the use of cisplatin
* Contraindication due to psychological, social, or geographical reasons that may impede proper monitoring of treatment
* Persons under guardianship or trusteeship, or prisoners of law

PRIOR CONCURRENT THERAPY:

* No prior treatment, including chemotherapy or radiotherapy
* No concurrent phenytoin, live attenuated vaccines, or parenteral aminoglycosides

Primary outcomes:
measure: Clinical and Radiological Complete Clinical Response (crCR) Rate at 3 Months
timeFrame: at 3 months after ETPF combination
Secondary outcomes:
measure: Complete Clinical Response (cCR)
timeFrame: at 3 months
measure: The 2-year Estimated Overall Survival (OS) Rate
timeFrame: 2 years
measure: Pathologic Response
timeFrame: after surgery of the primary tumor
measure: The 2-year Estimated Progression-free Survival (PFS)
timeFrame: 2 years
measure: Complete Radiological Response (rCR)
timeFrame: At 3 months after the end of 3 cycles of the ETPF combination
Other outcomes:
measure: Biomarkers Analysis - HPV Genotyping
timeFrame: correlative studies investigating HPV status in tumor and blood samples obtained prior to and after induction therapy were done for exploratory purposes as planned in the protocol
Locations:
city: Montmorency
country: France
facility: Hôpital Simone Veil
city: Paris
country: France
facility: Hôpital Privé St Joseph
city: Paris
country: France
facility: Hopital Europeen Georges Pompidou
city: Paris
country: France
facility: Hopital Bichat - Claude Bernard
city: Paris
country: France
facility: Hopital Tenon
city: Pierre Benite
country: France
facility: centre Hospitalier Lyon Sud
city: Saint Cloud
country: France
facility: Centre René Huguenin
city: Suresnes
country: France
facility: Hopital Foch
Study officials:
affiliation: Hopital Tenon
name: Jean Lacau Saint Guily, MD
role: PRINCIPAL_INVESTIGATOR
References: