Cetuximab and Radiation Therapy in Treating Patients With Stage III-IV Head and Neck Cancer

Rutgers The State University of New Jersey

Status: Terminated

Conditions: Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IVA Verrucous Carcinoma of the Larynx; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage III Verrucous Carcinoma of the Larynx; Tongue Cancer; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage IVB Verrucous Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Larynx; Stage IVA Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Hypopharynx

Treatments: Other: laboratory biomarker analysis; Radiation: external beam radiation therapy; Drug: cisplatin; Biological: cetuximab

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT02177838

NCI-2014-01303 (Registry Identifier)

P30CA072720 (U.S. NIH Grant/Contract)

Pro20150001420

031204 (Other Identifier)

Details and patient eligibility

About

This pilot clinical trial studies cetuximab and radiation therapy in treating patients with stage III-IV head and neck cancer. Monoclonal antibodies, such as cetuximab, may block tumor growth in different ways by targeting certain cells. Radiation therapy uses high energy x rays to kill tumor cells. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving cetuximab or cisplatin together with radiation therapy may kill more tumor cells.

Full description

PRIMARY OBJECTIVES:

I. 2 year (yr) locoregional control in cetuximab responders.

SECONDARY OBJECTIVES:

I. Assess secondary clinical endpoints such as the percent of patients receiving neoadjuvant cetuximab who progress by computed tomography (CT) Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria during the neoadjuvant cetuximab, the 2 yr locoregional control for non-responders to neoadjuvant cetuximab, and the complete response rate to positron emission tomography (PET)/computed tomography (CT) scan 3 months after the completion of radiation therapy for both responders and for non-responders to neoadjuvant cetuximab.

II. Analyze the relationship of known deoxyribonucleic acid (DNA) mutations in tumor per the FoundationOne genomic profile, and correlate to clinical endpoints such as locoregional control.

II. Analyze any changes in protein production at the tumor in response to 3 weeks of cetuximab.

III. Analyze any changes in protein production at the skin in response to 3 weeks of cetuximab.

IV. To investigate whether the tumor imaging characteristics including anatomical and molecular parameters evaluated by PET/CT, either alone or combined with other biomarkers can attribute to the better prediction for the clinical outcomes, as the response to neoadjuvant cetuximab; and the final clinical endpoint, the 2-year local regional controls.

OUTLINE:

Patients receive cetuximab intravenously (IV) over 60-120 minutes for 3 weeks. Patients then undergo external beam radiation therapy (EBRT) over 6-7 weeks. Patients achieving response continue weekly doses of cetuximab until radiation therapy is completed. Patients unable to achieve response or progression receive cisplatin IV over 1-2 hours on days 1, 22, and 43 of radiation therapy.

After completion of study treatment, patients are followed up every 3 months for 2 years.

Enrollment: 8 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Histologically proven squamous cell carcinoma of the oropharynx, hypopharynx or larynx
• Stage III/IVa/b squamous cell carcinoma (SCC) by American Joint Committee on Cancer (AJCC) 7 criteria (advanced, but not metastatic)
• Patients must give informed consent
• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status =< 2
• Platelets >= 100,000/uL
• Absolute neutrophil count (ANC) >= 1,500/uL
• Hemoglobin > 8 g/dl (use of transfusion to achieve this is acceptable)
• Total bilirubin < 2 X institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 X institutional ULN
• Serum creatinine < 2 x institutional ULN or creatinine clearance > 50 ml/min as determined by 24 hour collection or estimated by Cockcroft-Gault formula
• Estimated life expectancy of at least 12 weeks
• Negative pregnancy test

Exclusion criteria

• Patients may not have received previous therapy for their head and neck SCC, including chemotherapy, radiation therapy, or surgery beyond biopsy

• Second primary malignancy; exceptions are 1) patient had a second primary malignancy but has been treated and disease free for at least 3 years, 2) in situ carcinoma (e.g. in situ carcinoma of the cervix), 3) non-melanomatous carcinoma of the skin

• Patients with metastatic disease beyond the neck and supraclavicular region will be excluded

• Serious concomitant systemic disorders (including active infections) that would compromise the safety of the patient or compromise the patient's ability to complete the study, at the discretion of the investigator; this includes scleroderma

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to cetuximab or cisplatinum or other agents used in the study

• Women who are pregnant; women of childbearing age must agree to undergo a pregnancy test prior to therapy and to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation and for 6 months after; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately

• Patients with human immunodeficiency virus (HIV) infection are not automatically excluded, but must meet the following criteria: cluster of differentiation (CD)4 count is > 499/cu mm and their viral load is < 50 copies/ml; use of highly active anti-retroviral therapy (HAART) is allowed

• Patients who have had either myocardial infarction, coronary artery bypass graft, coronary artery stenting, hospital admission for heart related issues such as congestive heart failure or arrhythmia within the last 3 months, will not be allowed on protocol

• Grade 3-4 electrolyte abnormalities (Common Terminology Criteria for Adverse Events [CTCAE], version [v]. 4):

  • Serum calcium (ionized or adjusted for albumin) < 7 mg/dl (1.75 mmol/L) or > 12.5 mg/dl (> 3.1 mmol/L) despite intervention to normalize levels
  • Magnesium < 0.9 mg/dl (< 0.4 mmol/L) or > 3 mg/dl (> 1.23 mmol/L) despite intervention to normalize levels
  • Potassium < 3.5 mmol/L or > 6 mmol/L despite intervention to normalize levels
  • Sodium < 130 mmol/L or > 155 mmol/L despite intervention to normalize levels

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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8 participants in 1 patient group

Treatment (cetuximab, cisplatin, EBRT)

Experimental group

Description:

Patients receive cetuximab IV over 60-120 minutes for 3 weeks. Patients then undergo EBRT over 6-7 weeks. Patients achieving response continue weekly doses of cetuximab until radiation therapy is completed. Patients unable to achieve response or progression receive cisplatin IV over 1-2 hours on days 1, 22, and 43 of radiation therapy.

Treatment:

Biological: cetuximab

Drug: cisplatin

Radiation: external beam radiation therapy

Other: laboratory biomarker analysis