A Phase II Trial of Cetuximab and Bevacizumab in Patients With Recurrent or Metastatic Head and Neck Cancer

Phase 2

Completed

Brief Summary: The purpose of this study is to determine if the combination of two new drugs, cetuximab (Erbitux) and bevacizumab (Avastin) can increase the effectiveness of treatment for head and neck cancer. Cetuximab has recently been approved by the FDA for head and neck cancer (that is locally or regionally advanced) when used in combination with radiation therapy. Cetuximab is also approved by the FDA for the treatment of colorectal cancer

Detailed Description: Approximately 40,000 new cases of head and neck cancer are diagnosed annually in the United States 1. Squamous cell carcinomas account for more than 90% of head and neck cancer cases. Patients with squamous cell carcinoma of the head and neck (HNSCC) usually present with locoregionally advanced disease. Initial presentation with distant metastasis may occur in about 10% of all patients. However, recurrence of disease either in local or distant sites after potentially curative treatment with surgery, radiation, and/or chemotherapy occurs in more than 50% of patients. Therefore, the majority of patients with HNSCC develop recurrent or metastatic disease during the course of their illness. These patients have a dismal prognosis with a median survival of 6-9 months 2-4.

Active single agents in head and neck squamous cell carcinoma include methotrexate, bleomycin, cisplatin, carboplatin, 5-FU, paclitaxel, docetaxel, and CPT-11. A small randomized study showed that cisplatin monotherapy prolongs survival compared with best supportive care 5. Response rates for single agents range between 10-40% 2, 4, 6, 7. Combination chemotherapy with platinum agents, in spite of achieving higher response rates (about 30% in phase III trials), has not been shown to produce a survival benefit compared to single agents in randomized comparisons in recurrent/metastatic head and neck cancer 2, 4.

Recruitment & Eligibility

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Arm && Interventions

Group	Intervention	Description
Cetuximab plus bevacizumab	Bevacizumab	Cetuximab plus bevacizumab
Cetuximab plus bevacizumab	Cetuximab	Cetuximab plus bevacizumab

Primary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR)	Up to 5 years	ORR is the percentage of patients whose cancer shrunk or disappeared after study treatment. ORR was determined per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) for target lesions and assessed by computed tomography (CT) and/or magnetic resonance imaging (MRI) : Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR; Progressive Disease (PD): at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; Stable Disease (SD): neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.

Secondary Outcome Measures

Name	Time	Method
Progression-free Survival (PFS)	Up to 5 years	PFS is the length of time during and after treatment that patients are alive with the disease but it does not get worse. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) for target lesions and assessed by computed tomography (CT) and/or magnetic resonance imaging (MRI), Progressive Disease is defined as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
Overall Survival (OS)	Up to 5 years	The length of time from the start of study/treatment that diagnosed patients are still alive.
Change in Serum Cytokine Concentrations	Up to 5 years	Ratio of serum cytokines concentration after treatment with cetuximab and bevacizumab to baseline serum cytokines concentration, in picogram/milliliter (pg/ml) for 13 different cytokines. \[post-treatment (pg/ml) / baseline (pg/ml)\]
Disease Control Rate (DCR) ((Clinical Benefit Rate (CBR))	At 12 weeks	Disease Control Rate (DCR) (or Clinical Benefit Rate (CBR)), is defined as the percentage of patients with advanced or metastatic cancer who have achieved complete response, partial response and stable disease to cetuximab and bevacizumab. DCR = number of patients with (at least) partial response or stable disease / total number of evaluable patients

Locations (4): UPMC / UPMC Cancer Centers
🇺🇸
Pittsburgh, Pennsylvania, United States
Case Western Reserve University
🇺🇸
Cleveland, Ohio, United States
University of Michigan
🇺🇸
Ann Arbor, Michigan, United States
University of Texas MD Anderson
🇺🇸
Houston, Texas, United States