Clinical trial

Phase II Evaluation of Cetuximab (C225) Combined With Induction Paclitaxel and Carboplatin Followed by C225, Paclitaxel, Carboplatin, and Radiation for Stage III/IV Operable Squamous Cancer of the Head and Neck

Name

CDR0000378194

Description

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 paclitaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to damage tumor cells. Giving cetuximab with combination chemotherapy and radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving cetuximab after surgery may kill any tumor cells that remain. PURPOSE: This phase II trial is studying how well giving cetuximab together with combination chemotherapy and radiation therapy works in treating patients who are undergoing surgery for stage III or stage IV head and neck cancer.

Trial arms

Trial start

2005-01-06

Estimated PCD

2010-02-01

Trial end

2011-02-01

Status

Completed

Phase

Early phase I

Treatment

Cetuximab

Induction: An initial dose of cetuximab (C225) 400 mg/m2 (over 2 hours) was given week 1 only. Then, C225 was administered at dose of 250 mg/m2 (over 1 hour) weekly for 5 weeks. Concurrent Chemoradiation (Weeks 9-13): C225 was administered at 250 mg/m2/wk (over 1 hour). Restaging Biopsy of Primary Site (Week 14): Patients with positive biopsy of the primary site at week 7 or patients without a clinical complete response at the primary site after induction therapy were scheduled for re-biopsy of the primary site at week 14 after concurrent therapy (50 Gy). If the biopsy were negative after concurrent therapy, the patients were scheduled to continue concurrent therapy to complete radiation (68-72 Gy). Additional Concurrent Chemoradiation (weeks 15, 16 and 17): Concurrent therapy was consisted of C225 at 250mg/m2/week IV over 1 hour followed by paclitaxel 30mg/m2/week IV over 1 hour followed by carboplatin AUC = 1/week over 15 minutes and RT for three weeks.

Arms:

Cetuximab/Paclitaxel/Carboplatin

Other names:

C225, Erbitux

Carboplatin

Induction Therapy (Week 1-6): The induction chemotherapy starting at week 1 included paclitaxel 90 mg/m2 IV over 1 hour weekly and carboplatin AUC = 2 IV over 30 minutes weekly. The paclitaxel and carboplatin doses were given on the same day, 1 hour after C225 dose was administered. For paclitaxel and carboplatin therapy, rounding of doses (to next decimal if above 0.5 and to lower decimal if below 0.5) was permitted. Concurrent Chemoradiation (Weeks 9-13): Concurrent chemotherapy was consisted of paclitaxel following cetuximab at 30 mg/m2/wk (over 1 hour) and carboplatin following paclitaxel at AUC = 1/week (over 15 minutes). Additional Concurrent Chemoradiation (weeks 15, 16 and 17): Concurrent therapy was consisted of C225 at 250mg/m2/week IV over 1 hour followed by paclitaxel 30mg/m2/week IV over 1 hour followed by carboplatin AUC = 1/week over 15 minutes and RT for three weeks.

Arms:

Cetuximab/Paclitaxel/Carboplatin

Other names:

Paraplatin, Paraplatin-AQ

Paclitaxel

Arms:

Cetuximab/Paclitaxel/Carboplatin

Other names:

Taxol

Radiation therapy

Concurrent Chemoradiation (Weeks 9-13): Radiation was given at 200cGy/d/5 weeks for a total dose of 50Gy (5000 cGy). Patients with a negative initial biopsy at week 7 were scheduled to continue concurrent therapy to complete radiation (68-72Gy). If the biopsy was negative after concurrent therapy, the patients were scheduled to continue concurrent therapy to complete radiation (68-72 Gy). Additional Concurrent Chemoradiation (weeks 15, 16 and 17): Concurrent therapy was consisted of C225 at 250mg/m2/week IV over 1 hour followed by paclitaxel 30mg/m2/week IV over 1 hour followed by carboplatin AUC = 1/week over 15 minutes and RT for three weeks.

Arms:

Cetuximab/Paclitaxel/Carboplatin

Size

Primary endpoint

Event-free Survival Rate at 1 Year

Assessed at 1 year.

Eligibility criteria

INCLUSION CRITERIA: * Locally advanced (Stage III/IV), but potentially operable squamous cancer of the head and neck (exclude nasopharynx). Primary site biopsies must have had proven for cancer, nodal status, confirmed by clinical and pathologic exam with fine needle aspiration cytology recommended. * ECOG performance status 0 - 1. * Adequate laboratory index (ANC \> 1500/mm3, platelets \> 100,000/mm3, creatinine 1.5mg/dl, bilirubin 1.5mg/dl) completed within 4 weeks prior to registration. * Surgical resectability: * Included patients with operative stage III/IV disease, high likelihood of achieving R0 resection (complete resection with clean margins indicating NO residual cancer). * Measurable disease, biopsy proven at primary site. Patients with clinically palpable cervical nodes were to have evaluation by CT scan and fine needle aspiration (FNA) confirmation of disease. Patients with non-palpable neck nodes had CT determination. In the absence of clinically palpable nodes, radiographic findings were acceptable. * At least one objective measurable disease parameter in the primary site or neck. * Baseline measurements or evaluations must have had obtained within 4 weeks prior to registration in the study. * Age \> 18 years. * Women of childbearing potential and sexually active males were strongly advised to use an accepted and effective method of contraception. * Original diagnostic materials must have had submitted for baseline EGFR assessment by the designated laboratory. EXCLUSION CRITERIA: * Patients with fixed nodal metastases to spine or carotid artery, patients with invasion of root of tongue, pharyngeal muscle, post pharynx, or vertebral fascia or invasion of laryngeal cartilage into strap muscles or tracheal (\>1cm) invasion. * Prior chemotherapy, surgery radiation or immunotherapy for head and neck cancer. * Prior malignancies except in situ lobular breast carcinoma, in situ cervical carcinoma, basal cell cancers or previously excised and controlled cutaneous squamous cancer (\<200 mm thick) were permitted. * Significant history of cardiac disease i.e., uncontrolled hypertension, unstable angina, congestive heart failure, or uncontrolled arrhythmias. * Prior anti-epidermal growth factor receptor antibody therapy or therapy with a tyrosine kinase inhibitor including inhibitors targeting EGFR pathway. * Prior chimerized or murine monoclonal antibody therapy or known allergy to murine proteins or cremophor EL. * Pregnant or breast-feeding women. All females of childbearing potential must have had a blood test or urine study within 72 hours of study entry and must not have had started therapy until 5 days after registration was over to rule out pregnancy.

Protocol

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Updated at

2023-06-29

1 organization

3 drugs

1 indication

Organization

Eastern Cooperative Oncology Group

Drug

Indication

Drug

Drug