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

NCT00409565 | Completed Phase 2 Results

• 2 other identifiers: NCI-2009-00171NCI / CTEP Protocol # 7440
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 4

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

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

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  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.

  Up to 5 years

Secondary Outcomes (4)

• Progression-free Survival (PFS)

  Up to 5 years

• Overall Survival (OS)

  Up to 5 years

• Change in Serum Cytokine Concentrations

  Up to 5 years

• Disease Control Rate (DCR) ((Clinical Benefit Rate (CBR))

  At 12 weeks

Study Arms (1)

Cetuximab plus bevacizumab

EXPERIMENTAL

Cetuximab plus bevacizumab

Drug: Cetuximab; Drug: Bevacizumab

Interventions

Cetuximab 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

Also known as: Erbitux, C225

Cetuximab plus bevacizumab

Bevacizumab DRUG

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

Also known as: (rhuMAb VEGF, Avastin) (NSC 704865; IND 7921)

Cetuximab plus bevacizumab

Eligibility Criteria

• Age: 18 Years - 98 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

Eligibility Criteria Patients must have histologically or cytologically confirmed Squamous Cell Cancer of the Head and Neck either (a) metastatic (i.e. American Joint Committee on Cancer Staging System, 6th edition, stage IVC) or (b) recurrent, judged incurable by surgery or radiation. Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as \>20 mm with conventional techniques or as \>10 mm with CT scan). RECIST criteria will be used (see section 9). Therapeutic history in conformance with the following: No more than one prior adjuvant/neoadjuvant chemotherapy and/or concomitant chemoradiotherapy regimen that may have included biologic/targeted agent. No more than one prior regimen (chemotherapy or biologic/targeted) for recurrent/metastatic disease ECOG performance status of 0-2 (Karnofsky \> 60%; see Appendix A). Patients must have normal organ and marrow function as defined below: absolute neutrophil count \> 1,000/L platelets \> 75,000/L total bilirubin within normal institutional limits AST(SGOT)/ALT(SGPT) 5 X institutional upper limit of normal creatinine within normal institutional limits OR creatinine clearance \> 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal Urine protein should be screened by urine analysis for Urine Protein Creatinine (UPC) ratio (see Appendix). For UPC ratio \> 0.5, 24-hour urine protein should be obtained and the level should be \<1000 mg for patient enrollment. Note: UPC ratio of spot urine is an estimation of the 24 urine protein excretion - a UPC ratio of 1 is roughly equivalent to a 24-hour urine protein of 1 gm. UPC ratio is calculated using on of the following formula: \[urine protein\]/\[urine creatinine\] - if both protein and creatinine are reported in mg/Dl \[(urine protein) x0.088\]/\[urine creatinine\] - if urine creatinine is reported in mmol/L All patients should have baseline tumor tissue available for EGFR determination (therapeutic target of cetuximab) and biomarker studies. Patients without available tissue at baseline may undergo tumor biopsy. Patients who provide consent and have accessible tumors will have a repeat biopsy 14 days (an interval between 12-16 days is acceptable) post initiation of therapy. Priority for study entry will be given to patients with easily accessible tumor and who consent to repeat biopsy. Study entry will not be restricted to patients who agree to further biopsies. If a patient enrolls on study and later refuses biopsy (excluding diagnostic), he/she may remain on study. No prior treatment with cetuximab or bevacizumab or other EGFR or VEGF targeting agents. Patients should not have had chemotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) and biologic/targeted agents within 3 weeks. At least 3 months should have elapsed after prior therapy with monoclonal antibodies. At least 3 weeks should have elapsed from prior radiotherapy. Patients must have no history of gross hemoptysis (defined as bright red blood of a ½ teaspoon or more) or coagulopathy. Patients with history of major tumor-related bleeding that is not controlled despite locoregional treatment or at high risk of recurrent tumor-related bleeding will be excluded. 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.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (4)

University of Michigan

Ann Arbor, Michigan, 48109-0848, United States

Location

Case Western Reserve University

Cleveland, Ohio, 44106, United States

Location

UPMC / UPMC Cancer Centers

Pittsburgh, Pennsylvania, 15232, United States

Location

University of Texas MD Anderson

Houston, Texas, 77030, United States

Location

Related Publications (1)

• 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.

  PMID: 22898037 RESULT

MeSH Terms

Conditions

Head and Neck Neoplasms; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck

Interventions

Cetuximab; Bevacizumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms, Squamous Cell

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Michael Gibson, MD
• Organization: University of Pittsburgh Cancer Institute

gibsonmk@upmc.edu

412-692-2600

Study Officials

• Michael Gibson, MD

  Eastern Cooperative Oncology Group

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 7, 2006
• First Posted: December 11, 2006
• Study Start: September 1, 2006
• Primary Completion: February 1, 2012
• Study Completion: February 1, 2012
• Last Updated: October 20, 2017
• Results First Posted: July 12, 2016

Record last verified: 2017-09

Locations

US (4)