Radiation Therapy With Cisplatin or Cetuximab in Treating Patients With Oropharyngeal Cancer
Condition: Head and Neck Cancer; Precancerous Condition
MeSH terms: Precancerous Conditions
Intervention: cetuximab; cisplatin; IMRT
Intervention description: 400 mg/m2 IV 5-7 days before IMRT then 250 mg/m2 IV weekly for 7 weeks; 100 mg/m2 IV on days 1 and 22 of IMRT; 35 fractions over 6 weeks, 6 fractions per week, 2 Gray per fraction to total dose of 70 Gy.
Intervention MeSH terms: Cetuximab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 987.0
Sex: All
Minimum age: 18 Years
Maximum age: 120 Years
Healthy volunteers: No
Keywords: stage III squamous cell carcinoma of the oropharynx; stage IV squamous cell carcinoma of the oropharynx; human papilloma virus infection

Summary:

      RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells and shrink tumors.
      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. 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. It is not yet known whether radiation therapy is more
      effective with cisplatin or cetuximab in treating oropharyngeal cancer.

      PURPOSE: This phase III trial is studying radiation therapy with cisplatin or cetuximab to
      see how well it works in treating patients with oropharyngeal cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Pathologically (histologically or cytologically) proven diagnosis of squamous cell
             carcinoma (including the histological variants papillary squamous cell carcinoma and
             basaloid squamous cell carcinoma) of the oropharynx (tonsil, base of tongue, soft
             palate, or oropharyngeal walls).

          2. Patients must be positive for p16, determined by central review prior to
             randomization.

          3. Patients must have clinically or radiographically evident measurable disease at the
             primary site or at nodal stations. Tonsillectomy or local excision of the primary
             without removal of nodal disease is permitted, as is excision removing gross nodal
             disease but with intact primary site. Limited neck dissections retrieving ≤ 4 nodes
             are permitted and considered as non-therapeutic nodal excisions. Fine needle
             aspirations of the neck are insufficient due to limited tissue for retrospective
             central review. Biopsy specimens from the primary or nodes measuring at least 3-5 mm
             are required.

          4. Clinical stage T1-2, N2a-N3 or T3-4, any N (AJCC, 7th ed.; see Appendix III),
             including no distant metastases, based upon the following minimum diagnostic workup:

               -  General history and physical examination by a radiation oncologist and medical
                  oncologist within 8 weeks prior to registration;

               -  Examination by an ear, nose, and throat (ENT) or head and neck surgeon, including
                  laryngopharyngoscopy (mirror and/or fiberoptic and/or direct procedure) within 8
                  weeks prior to registration;

               -  One of the following combinations of imaging is required within 8 weeks prior to
                  registration:

                    1. A computerized tomography (CT) scan of the neck (with contrast) and a chest
                       CT scan (with or without contrast);

                    2. or a magnetic resonance imaging (MRI) scan of the neck (with contrast) and a
                       chest CT scan (with or without contrast);

                    3. or a CT scan of neck (with contrast) and a positron emission tomography
                       (PET)/CT of neck and chest (with or without contrast);

                    4. or an MRI of the neck (with contrast) and a PET/CT of neck and chest (with
                       or without contrast).

             Note: A CT scan of neck and/or a PET/CT performed for radiation planning and read by a
             radiologist may serve as both staging and planning tools.

          5. Zubrod Performance Status 0-1 within 2 weeks prior to registration

          6. Age ≥ 18;

          7. Complete blood count (CBC)/differential obtained within 2 weeks prior to registration
             on study, with adequate bone marrow function, defined as follows:

               -  Absolute neutrophil count (ANC) > 1,500 cells/mm3;

               -  Platelets > 100,000 cells/mm3;

               -  Hemoglobin (Hgb) > 8.0 g/dl; Note: The use of transfusion or other intervention
                  to achieve Hgb > 8.0 g/dl is acceptable.

          8. Adequate hepatic function, defined as follows:

               -  Bilirubin < 2 mg/dl within 2 weeks prior to registration;

               -  Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 3 x the
                  upper limit of normal within 2 weeks prior to registration;

          9. Adequate renal function, defined as follows:

             • Serum creatinine < 1.5 mg/dl within 2 weeks prior to registration or 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
             (CCr male)

         10. Patients must provide their smoking history (for stratification) via the
             computer-assisted self interview (CASI) head and neck risk factor survey tool.

         11. Negative serum pregnancy test within 2 weeks prior to registration for women of
             childbearing potential;

         12. 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 and until at least 60 days following the last study treatment.

         13. Patients who are human immunodeficiency virus (HIV) positive but have no prior
             acquired immune deficiency syndrome (AIDS) -defining illness and have CD4 cells of at
             least 350/mm3 are eligible. Patient HIV status must be known prior to registration.
             Patients must not be sero-positive for Hepatitis B (Hepatitis B surface antigen
             positive or anti-hepatitis B core antigen positive) or sero-positive for Hepatitis C
             (anti-Hepatitis C antibody positive). However, patients who are immune to hepatitis B
             (anti-Hepatitis B surface antibody positive) are eligible (e.g. patients immunized
             against hepatitis B). HIV-positive patients must not have multi-drug resistant HIV
             infection or other concurrent AIDS-defining conditions.

         14. Patient must provide study specific informed consent prior to study entry, including
             consent for mandatory submission of tissue for required, central p16 review and
             consent to participate in the computer-assisted self interview (CASI) survey questions
             regarding smoking history.

        Exclusion Criteria:

          1. Cancers considered to be from an oral cavity site (oral tongue, floor mouth, alveolar
             ridge, buccal or lip), nasopharynx, hypopharynx, or larynx, even if p16 positive, are
             excluded. Carcinoma of the neck of unknown primary site origin (even if p16 positive)
             are excluded from participation.

          2. Stage T1-2, N0-1;

          3. Distant metastasis or adenopathy below the clavicles;

          4. Gross total excision of both primary and nodal disease; this includes tonsillectomy,
             local excision of primary site, and nodal excision that removes all clinically and
             radiographically evident disease.

          5. Simultaneous primaries or bilateral tumors;

          6. Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free
             for a minimum of 3 years (For example, carcinoma in situ of the breast, oral cavity,
             or cervix are all permissible);

          7. Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a
             different cancer is allowable;

          8. Prior radiotherapy to the region of the study cancer that would result in overlap of
             radiation therapy fields;

          9. Severe, active co-morbidity, defined as follows:

               -  9.1 Unstable angina and/or congestive heart failure requiring hospitalization
                  within the last 6 months;

               -  9.2 Transmural myocardial infarction within the last 6 months;

               -  9.3 Acute bacterial or fungal infection requiring intravenous antibiotics at the
                  time of registration;

               -  9.4 Chronic Obstructive Pulmonary Disease exacerbation or other respiratory
                  illness requiring hospitalization or precluding study therapy within 30 days of
                  registration;

               -  9.5 Hepatic insufficiency resulting in clinical jaundice and/or coagulation
                  defects; note, however, that laboratory tests for liver function and coagulation
                  parameters are not required for entry into this protocol.

               -  9.6 Acquired Immune Deficiency Syndrome (AIDS) based upon current Centers for
                  Disease Control and Prevention (CDC) definition with immune compromise greater
                  than that noted in Section 3.1.13; 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.

         10. Pregnancy 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.

         11. Prior allergic reaction to cisplatin or cetuximab;

         12. Prior cetuximab or other anti-EGFR therapy.