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

NCT ID: NCT00409565

Last Updated: 2017-10-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 48 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-09-30
• Study Completion Date: 2012-02-29

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.

Conditions

Head and Neck Cancer; Squamous Cell Carcinoma

Keywords

head and neck cancer; cetuximab; bevacizumab; squamous cell carcinoma; SCCHN; Squamous Cell Carcinoma of the Head and Neck

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cetuximab plus bevacizumab

Cetuximab plus bevacizumab

Group Type: EXPERIMENTAL

Cetuximab

Intervention Type: DRUG

• Cetuximab 400 mg/m2 IV over 120 minutes on day 1 of cycle 1 ONLY
• Cetuximab dose will be 250 mg/m2 IV over 60 minutes weekly on ALL subsequent administrations

Bevacizumab

Intervention Type: DRUG

Once every 3 weeks, 15 mg/kg of bevacizumab will be given by IV infusion after cetuximab has been given

Interventions

Cetuximab

• Cetuximab 400 mg/m2 IV over 120 minutes on day 1 of cycle 1 ONLY
• Cetuximab dose will be 250 mg/m2 IV over 60 minutes weekly on ALL subsequent administrations

Intervention Type: DRUG

Bevacizumab

Once every 3 weeks, 15 mg/kg of bevacizumab will be given by IV infusion after cetuximab has been given

Intervention Type: DRUG

Other Intervention Names

Erbitux, C225; (rhuMAb VEGF, Avastin) (NSC 704865; IND 7921)

Eligibility Criteria

Exclusion Criteria

Patients should not have a history of thrombosis (e.g. pulmonary embolism or deep venous thrombosis) and should not be on therapeutic anticoagulation (prophylactic use of warfarin 1 mg per day is allowed) and INR should be less than 1.5 at registration.

Patients with history of hypertension must be well-controlled (≤150/100) on a stable regimen of anti-hypertensive therapy.

Patients with tumors that invaded major vessels (e.g. the carotid) as shown unequivocally by imaging studies will be excluded due to the possibility of increased risk for tumor bleeding with bevacizumab therapy.

No major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study enrollment, or anticipation of need for major surgical procedure during the course of the study. No history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days prior to registration. No serious non-healing wound, ulcer, or bone fracture.

No unstable angina or myocardial infarction within the previous 6 months; no uncontrolled hypertension; no symptomatic congestive heart failure; no serious cardiac arrhythmia requiring medication; no clinically significant peripheral vascular disease; no history of any CNS cerebrovascular ischemia or stroke within the last 6 months; no active serious infection.

No other coexisting medical condition that would preclude full compliance with the study.

Patients may not be receiving any other investigational agents.

Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because of increased risks with bevacizumab.

Patients should not have a history of prior severe infusion reaction to a monoclonal antibody. Patients with known hypersensitivity of Chinese hamster ovary cell products or other recombinant human antibodies.

No history of prior malignancy, with the exception of curatively treated squamous cell or basal carcinoma of the skin or in situ cervical cancer, unless there is a 3-year disease-free interval.

Age > 18 years. Because no dosing or adverse event data are currently available on the use of cetuximab and bevacizumab in patients <18 years of age, children are excluded from this study but will be eligible for future pediatric single-agent trials, if applicable.

Ability to understand and the willingness to sign a written informed consent document.

Pregnant women are excluded from this study because cetuximab and bevacizumab have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with cetuximab and bevacizumab, breastfeeding should be discontinued if the mother is treated with cetuximab and bevacizumab. The effects of cetuximab and bevacizumab on the developing human fetus at the recommended therapeutic dose are unknown. For this reason women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while in this study, she should inform her treating physician immediately.

HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible drug interactions with cetuximab and bevacizumab. Appropriate studies will be undertaken in patients receiving combination anti-retroviral therapy when indicated.

Inclusion of Women and Minorities

Both men and women and members of all ethnic groups are eligible for this trial. The proposed study population is illustrated in the table below.

Inclusion of Women in Plan: The gender distribution of our head and neck cancer patients is detailed in the table below. All efforts are made to recruit women patients with head and neck cancer to the University of Pittsburgh Medical Center.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 98 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michael Gibson, MD

Role: PRINCIPAL_INVESTIGATOR

Eastern Cooperative Oncology Group

Locations

University of Michigan

Ann Arbor, Michigan, United States

Case Western Reserve University

Cleveland, Ohio, United States

UPMC / UPMC Cancer Centers

Pittsburgh, Pennsylvania, United States

University of Texas MD Anderson

Houston, Texas, United States

Countries

United States

References

Argiris A, Kotsakis AP, Hoang T, Worden FP, Savvides P, Gibson MK, Gyanchandani R, Blumenschein GR Jr, Chen HX, Grandis JR, Harari PM, Kies MS, Kim S. Cetuximab and bevacizumab: preclinical data and phase II trial in recurrent or metastatic squamous cell carcinoma of the head and neck. Ann Oncol. 2013 Jan;24(1):220-5. doi: 10.1093/annonc/mds245. Epub 2012 Aug 16.

Reference Type: RESULT

PMID: 22898037 (View on PubMed)

Other Identifiers

NCI / CTEP Protocol # 7440

Identifier Type: -

Identifier Source: secondary_id

NCI-2009-00171

Identifier Type: -

Identifier Source: org_study_id

NCT00407810

Identifier Type: -

Identifier Source: nct_alias