Radiation Therapy and Cisplatin With or Without Cetuximab in Treating Patients With Stage III or Stage IV Head and Neck Cancer
Condition: Head and Neck Cancer
MeSH terms: Head and Neck Neoplasms
Intervention: cetuximab; cisplatin; Accelerated Fractionation by Concomitant Boost; Intensity-modulated radiation therapy
Intervention description: Cetuximab 400 mg/m^2 IV loading dose 5-7 days before start of radiation therapy, then 250 mg/m^2 IV weekly for 7 weeks; Cisplatin 100 mg/m^2 IV on days 1 and 22; 3DCRT 54 Gy in 30 1.8 Gy fractions over 6 weeks with boost 18 Gy in 12 1.5 Gy fractions for last 12 days, for a total of 72 Gy in 42 fractions over 6 weeks; 70 Gy in 35 2.0 Gy fractions over 6 weeks with 6 fractions per week (on Saturday or as second daily fraction) in 5 of the 6 weeks.
Intervention MeSH terms: Cetuximab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 940.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: stage III squamous cell carcinoma of the hypopharynx; stage IV squamous cell carcinoma of the hypopharynx; stage III squamous cell carcinoma of the larynx; stage IV squamous cell carcinoma of the larynx; stage III squamous cell carcinoma of the oropharynx; stage IV squamous cell carcinoma of the oropharynx

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.
    

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.