Cetuximab and Combination Chemotherapy in Patients With Stage III-IV Resectable Oropharynx Cancer

Head and Neck Cancer Clinical Trial

— ECHO-07  

Official title:

Induction Chemotherapy With Cetuximab, Docetaxel, Cisplatin, and Fluorouracil (ETPF) in Patient With Resectable Stage III-IV Squamous Cell Carcinoma of the Oropharynx

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00665392
• Other study ID #: CDR0000593027
• Secondary ID: GERCOR-ECHO-07-1
• Status: Completed
• Phase: Phase 2
• Start date: February 2008
• Est. completion date: July 2012

Study information

• Verified date: August 2012
• Source: GERCOR - Multidisciplinary Oncology Cooperative Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: July 2012
• Est. primary completion date: July 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Head and Neck Cancer
• Head and Neck Neoplasms

Intervention

Drug:
• cisplatin
75 mg/m², day 1. 3 cycles
• docetaxel
75 mg/m² Day 1. 3 cycles
• fluorouracil
750 mg/m² day 1 to day 5. 3 cycles
• Cetuximab
400 mg/m² Day 1, 250 mg/m² Day 8 and Day 15. 3 cycles.

Locations

Country	Name	City	State
France	Hôpital Simone Veil	Montmorency
France	Hopital Bichat - Claude Bernard	Paris
France	Hopital Europeen Georges Pompidou	Paris
France	Hôpital Privé St Joseph	Paris
France	Hopital Tenon	Paris
France	centre Hospitalier Lyon Sud	Pierre Benite
France	Centre René Huguenin	Saint Cloud
France	Hopital Foch	Suresnes

Sponsors (1)

Lead Sponsor	Collaborator
GERCOR - Multidisciplinary Oncology Cooperative Group

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Biomarkers Analysis - HPV Genotyping		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
Primary	Clinical and Radiological Complete Clinical Response (crCR) Rate at 3 Months	The evaluation of tumor response rate was assessed by computed tomography scan of the neck and chest at Baseline, then at 3 months from inclusion using RECIST1.0 criteria and clinical examination	at 3 months after ETPF combination
Secondary	Complete Clinical Response (cCR)	Clinical complete response (cCR) is defined by: Disappearance of all clinical evidence of visible tumor,; Disappearance of all palpable residual infiltration,; Disappearance of all evidence of residual visible tumor on CT scan in pharynx and parapharyngeal space,; Complete symmetric remobilization of the tongue and amygdala.; Disappearance of pre-existing trismus.; Negative control biopsy.; The evaluation of tumor response rate was assessed by computed tomography scan of the neck and chest at Baseline, then at 3 months from inclusion using RECIST1.0 criteria and clinical examination	at 3 months
Secondary	The 2-year Estimated Overall Survival (OS) Rate	2-year OS measured survival at 2 years from randomization.	2 years
Secondary	Pathologic Response	On primary tumor resected : measure of persistence or not of tumoral lesion, histological type, size and quality of the excision piece; A pathological complete response is defined as no viable tumour cells detected on histological examination post surgery.	after surgery of the primary tumor
Secondary	The 2-year Estimated Progression-free Survival (PFS)	2-year PFS measured survival at 2 years from randomization.	2 years
Secondary	Complete Radiological Response (rCR)	Radiological response is defined according to RECIST 1.0 criteria: Complete response (CR): disappearance of all target lesions; Partial response (PR): at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter,; Progressive disease (PD): at least a 20% increase in the sum of the longest diameter of target the appearance of one or more new lesions,; Stable disease (SD): neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum longest diameter since the treatment started	At 3 months after the end of 3 cycles of the ETPF combination

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