Radiation Therapy and Cisplatin With or Without Cetuximab in Treating Patients With Stage III or Stage IV Head and Neck Cancer | NCT00265941 | Trialant

Radiation Therapy and Cisplatin With or Without Cetuximab in Treating Patients With Stage III or Stage IV Head and Neck Cancer | NCT00265941 | Trialant

Official Title: A Randomized Phase III Trial of Concurrent Accelerated Radiation and Cisplatin Versus Concurrent Accelerated Radiation, Cisplatin, and Cetuximab (C225) [Followed by Surgery for Selected Patients] for Stage III and IV Head and Neck Carcinomas
Brief Summary: RATIONALE: 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 or by stopping them from dividing. Cisplatin may also make tumor cells more sensitive to radiation therapy. 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. Giving radiation therapy and cisplatin together with cetuximab may kill more tumor cells. It is not yet known whether radiation therapy and cisplatin are more effective with or without cetuximab in treating head and neck cancer.

PURPOSE: This randomized phase III trial is studying radiation therapy, cisplatin, and cetuximab to see how well they work compared to radiation therapy and cisplatin in treating patients with stage III or stage IV head and neck cancer.
Detailed Description: OBJECTIVES:

Primary

Evaluate whether the addition of cetuximab to a concurrent radiation-cisplatin regimen will improve progression-free survival in patients with stage III or IV squamous cell carcinoma of the oropharynx, hypopharynx, or larynx.

Secondary

Determine the impact of the addition of cetuximab to a concurrent radiation-cisplatin regimen on overall survival, local-regional control, acute and late toxic effects, quality of life, and health utilities in these patients.

Correlate the expression of epidermal growth factor receptor (EGFR) and its down-stream molecules with outcome in patients participating in this component of the trial.

Correlate pre-treatment positron emission tomography (PET) scan findings with progression-free survival, overall survival, and local-regional control in patients participating in this component of the trial.

Correlate post-treatment PET scan findings with nodal response and nodal relapse in patients participating in this component of the trial.

OUTLINE: This is a randomized, controlled, multicenter study. Patients are stratified according to primary site (larynx vs non-larynx), nodal stage (N0 vs N1, N2a, N2b vs N2c, N3), Zubrod performance status (0 vs 1), use of intensity modulated radiotherapy (IMRT) (no vs yes), and pre-treatment PET/CT scan (no vs yes). Patients are randomized to 1 of 2 treatment arms.

NOTE: *A neck dissection is optional for patients with multiple lymph nodes or lymph nodes > 3 cm in diameter who achieve a complete clinical and radiographic response in the neck.

Quality of life is assessed at baseline, once during the last 2 weeks of treatment, at 3 and 12 months from the start of treatment, and then annually for 4 years.

After completion of study treatment, patients are followed periodically for 5 years and then annually thereafter.

Ages Eligible for Study: Adult (18-64)Older Adult (65+)
Sexes Eligible for Study: All
Accepts Healthy Volunteers: No
Eligibility Criteria: Inclusion criteria:

Pathologically (histologically or cytologically) proven (from primary lesion and/or lymph nodes) diagnosis of squamous cell carcinoma of the oropharynx, hypopharynx, or larynx;

Selected stage III or IV disease (T2N2-3M0, T3-4 any N M0); Note: Patients with T1, any N, or T2N1 tumors are not eligible.

Appropriate stage for protocol entry, including no distant metastases, based upon the following minimum diagnostic workup:

History/physical examination within 4 weeks prior to registration, including assessment of weight and weight loss in past 6 months and an examination by a Medical Oncologist;

Chest x-ray (or Chest CT scan or PET/CT scan) within 6 weeks prior to registration;

CT scan or MRI of the head and neck (of the primary tumor and neck nodes) or PET/CT scan within 6 weeks prior to registration; see Section 6.11 for details of PET scans. Note: A PET/CT can only be used instead of a CT scan or MRI if the CT is a high quality scan with contrast.

Left ejection fraction determined by echocardiogram and/or multiple gated acquisition (MUGA) technique within 12 weeks of registration;

Zubrod Performance Status 0-1;

Age > 18;

Adequate bone marrow function, defined as follows:

Absolute neutrophil count (ANC) > 1,800 cells/mm3 based upon CBC/differential obtained within 2 weeks prior to registration on study;

Platelets > 100,000 cells/mm3 based upon complete blood count (CBC)/differential obtained within 2 weeks prior to registration on study;

Hemoglobin > 8.0 g/dl based upon CBC/differential obtained within 2 weeks prior to registration on study (Note: The use of transfusion or other intervention to achieve Hgb > 8.0 g/dl is acceptable.)

Adequate hepatic function, defined as follows:

Bilirubin < 1.5 mg/dl within 2 weeks prior to registration on study; For patients with Gilbert's disease as the sole cause of elevated bilirubin, please contact the PI, Dr. Ang.

Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 2x the upper limit of normal within 2 weeks prior to registration on study;

Adequate renal function, defined as follows:

Serum creatinine < 1.5 mg/dl within 2 weeks prior to registration

Creatinine clearance (CCr) ≥ 50 ml/min within 2 weeks prior to registration determined by 24-hour collection or estimated by Cockcroft-Gault formula: CCr male = [(140 - age) x (wt in kg)]/[(Serum Cr mg/dl) x (72)] CCr female = 0.85 x (CrCl male)

Pregnancy test within 2 weeks prior to registration for women of childbearing potential;

Women of childbearing potential and male participants must agree to use a medically effective means of birth control throughout their participation in the treatment phase of the study (until at least 60 days following the last study treatment);

Patient must sign study specific informed consent prior to study entry.

Exclusion criteria:

Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years;

Patients with simultaneous primaries or bilateral tumors are excluded.

Gross total excision (e.g., by tonsillectomy) of the primary tumor; however, partial removal of the tumor to alleviate an impending airway obstruction does not make the patient ineligible.

Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a different cancer is allowable;

Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields;

Primary site of tumor of oral cavity, nasopharynx, sinuses, or salivary glands;

Initial surgical treatment, excluding diagnostic biopsy of the primary site or nodal sampling of neck disease; radical or modified neck dissection is not permitted.

Severe, active co-morbidity, defined as follows:

Current uncontrolled cardiac disease; i.e., uncontrolled hypertension, unstable angina, recent myocardial infarction (within prior 6 months), uncontrolled congestive heart failure, and cardiomyopathy with decreased ejection fraction;

Left Ventricular Ejection Fraction < 45%;

Transmural myocardial infarction within the last 6 months;

Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration;

Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration;

Acquired Immune Deficiency Syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; note, however, that HIV testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive. Protocol-specific requirements may also exclude immuno-compromised patients.

Any uncontrolled condition, which in the opinion of the investigator, would interfere in the safe and timely completion of study procedures;

CTCAE, v. 3.0 grade 3-4 electrolyte abnormalities:

Calcium < 7 mg/dl or > 12.5 mg/dl;

Glucose < 40 mg/dl or > 250 mg/dl;

Magnesium < 0.9 mg/dl or > 3 mg/dl;

Potassium < 3 mmol/L or > 6 mmol/L;

Sodium < 130 mmol/L or > 155 mmol/L

Pregnant or lactating women or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic.

Prior allergic reaction to the study drug(s) involved in this protocol;

Prior therapy that specifically and directly targets the EGFR pathway;

Prior severe infusion reaction to a monoclonal antibody.