Cetuximab, EGFR Antisense DNA, and Radiation Therapy in Treating Patients With Stage III-IV Squamous Cell Cancer of the Head and Neck

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Basic Trial Information

PhaseTypeStatusAgeTrial IDs
Phase II, Phase IBiomarker/Laboratory analysis, TreatmentActive18 and overUPCI 06-121
NCI-2013-00329, NCT00903461

Trial Description

Summary

This phase I/II trial studies the side effects and best way to give cetuximab and epidermal growth factor receptor (EGFR) antisense deoxyribonucleic acid (DNA) and radiation therapy and to see how well it works in treating patients with stage III-IV squamous cell cancer of the head and neck. 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. Biological therapies, such as EGFR antisense DNA, may interfere with the growth of tumor cells and slow the growth of head and neck cancer. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving cetuximab, EGFR antisense DNA, and radiation therapy together may kill more tumor cells.

Further Study Information

PRIMARY OBJECTIVES:

I. To evaluate the safety of the combination of intratumoral EGFR antisense (AS) DNA with standard cetuximab and radiation.

II. To evaluate the locoregional control in elderly or cisplatin-ineligible patients with locally advanced squamous cell cancer of the head and neck (SCCHN) treated with intratumoral EGFR antisense DNA combined with standard radiation plus cetuximab.

III. To evaluate the toxicities associated with the above treatment.

IV. To evaluate other efficacy parameters, including the objective response rate, distant control and overall progression-free survival, and overall survival.

V. To determine the effect of EGFR antisense therapy on EGFR and EGFR-related biomarkers.

VI. To examine the transfection of the EGFR antisense gene therapy in vivo.

OUTLINE:

Patients receive cetuximab intravenously (IV) over 120 minutes 2 on week 1 and then once weekly over 60 minutes on weeks 2-9. Patients also receive EGFR antisense DNA by intratumoral injection once weekly on weeks 1-7, and undergo radiation therapy daily, 5 days per week, on weeks 3-9.

After completion of study treatment, patients are followed every 3 months for 2 years, every 6 months for 3 years, and every year for up to 5 years.

Eligibility Criteria

Inclusion Criteria:

First stage:

Patients with American Joint Committee on Cancer (AJCC) 6th edition stage IVA-IVC or recurrent or metastatic head and neck cancer will be eligible

Second stage (Phase II part): Patients with AJCC 6th edition stage III-IVB (T1-T4, N1-3, M0) head and neck cancer, except World Health Organization (WHO) type II and III nasopharyngeal cancer, including unknown primary tumors

Histologically or cytologically confirmed diagnosis of squamous cell carcinoma or variants or poorly differentiated carcinoma

Unidimensionally measurable disease (Response Evaluation Criteria in Solid Tumors [RECIST] criteria)

Age limits:

Age 70 or older with performance status 0-2

Patients of any age (but 18 years of age or older) with Eastern Cooperative Oncology Group (ECOG) performance status of 2

Patients of any age (but 18 years of age or older) unsuitable for concurrent cisplatin due to:

  • Calculated creatinine clearance of 20-60 mL/min, or
  • Severe cardiopulmonary disease, or
  • Other end-organ dysfunction that precludes the use of cisplatin chemotherapy but does not preclude the administration of cetuximab or intratumoral EGFR antisense

In the second stage of the study, therapy will be administered with a curative intent and patients should not have recurrent disease or distant metastasis

Primary tumor and/or lymphadenopathy should be technically suitable for intratumoral injections; the otolaryngologist specialist on the head and neck team will determine this feasibility

Participating patients should agree to undergo a tumor biopsy at baseline as well as approximately 2 weeks later as specified in study schema

Prior treatment:

First stage: any prior treatment, except prior therapy which specifically and directly targets the EGFR pathway, administered within the last 6 months

Second stage: no prior chemotherapy, biologic/molecular targeted therapy (including any prior therapy which specifically and directly targets the EGFR pathway), or radiotherapy for head and neck cancer

Prior surgical therapy will consist only of incisional or excisional biopsy, including tonsillectomy, and organ sparing procedures, including neck dissection; any non-biopsy surgical procedure for head and neck cancer must have taken place at least one month before initiating protocol treatment, at the treating physician’s discretion

Absolute neutrophil count >= 1,000/μL

Platelets >= 75,000/μL

Hemoglobin >= 10 g/dL

Total bilirubin < 2 x upper normal institutional limits

Creatinine clearance > 20 mL/min

Women of childbearing 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, and for 3 months after completing study treatment; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately

Informed consent must be obtained from all patients prior to beginning therapy; patients should have the ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

Severe renal insufficiency (creatinine clearance < 20 mL/min)

Treatment with anticoagulants, except when used to maintain the patency of a central venous line, or international normalized ratio (INR) > 1.5, or partial thromboplastin time (PTT) ratio > 1.5

Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements

Significant history of uncontrolled cardiac disease; i.e., uncontrolled hypertension, unstable angina, uncontrolled congestive heart failure

Patients may not be receiving any other investigational agents

No history of prior malignancy, with the exception of curatively treated squamous cell or basal carcinoma of the skin or in situ cervical cancer, ductal carcinoma in situ (DCIS) or lobular carcinoma in situ (LCIS) of the breast, localized early stage prostate cancer, or malignancy that has been treated with a curative intent with a 3-year disease-free survival

Pregnant women are excluded from this study because cetuximab, EGFR AS, and radiation 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 EGFR AS, breastfeeding should be discontinued if the mother is treated with cetuximab; the effects of cetuximab and EGFR AS 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

Human immunodeficiency virus (HIV)-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible drug interactions with cetuximab

Prior severe infusion reaction to a monoclonal antibody

Patients who are not informed of and are not willing to comply with the investigational nature of the study and have not signed a written informed consent in accordance with institutional and good clinical practice guidelines

Trial Contact Information

Trial Lead Organizations / Sponsors / Collaborators

University of Pittsburgh Cancer Institute (UPCI)

  • National Cancer Institute
Jennifer Rubin Grandis, Principal Investigator

Trial Sites

U.S.A.

Pennsylvania
Pittsburgh

University of Pittsburgh Cancer Institute (UPCI)

Jennifer Rubin Grandis
Ph: 412-647-8073
Email: grandisjr@upmc.edu

Jennifer Rubin Grandis
Principal Investigator

Link to the current ClinicalTrials.gov record.
NLM Identifier NCT00903461

Note: Information about participating sites on pharmaceutical industry trials may be incomplete. Please visit the ClinicalTrials.gov record via the link above for more information about participating sites.