Trial of Postoperative Radiation, Cisplatin, and Panitumumab in Locally Advanced Head and Neck Cancer
Condition: Cancer of Head; Cancer of Head and Neck; Cancer of Neck; Cancer of the Head; Cancer of the Head and Neck; Cancer of the Neck; Head and Neck Cancer; Head Cancer; Head Neoplasms; Head, Neck Neoplasms; Neck Cancer; Neck Neoplasms; Neoplasms, Head; Neoplasms, Head and Neck; Neoplasms, Neck; Neoplasms, Upper Aerodigestive Tract; UADT Neoplasms; Upper Aerodigestive Tract Neoplasms
MeSH terms: Neoplasms; Head and Neck Neoplasms
Intervention: Panitumumab; Cisplatin; Radiation Therapy
Intervention description: Panitumumab, starting dose, 2.5mg/kg will be given as an intravenous infusion (IV) through a vein in your arm, once a week before radiation and chemotherapy for 6 weeks; treatment takes about an hour.
The panitumumab dose will be calculated based on the subject's actual weekly body weight; Cisplatin, 30 mg/m2 will be given as an intravenous infusion (IV) through a vein in your arm, once a week before radiation therapy and after panitumumab for 6 weeks; treatment takes about an hour; Radiation Therapy 60-66 Gy/200 cGy/daily, five days a week, Monday through Friday, except on weekends and holidays, for six weeks; treatments take about 20 minutes.
Radiation will be administered either prior to chemo treatment or after chemo treatment as long as radiation is given on the same day.
Intervention MeSH terms: Cisplatin; Panitumumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 46.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: panitumumab; cisplatin; radiation

Summary:

      The objectives for this study is as follows:

        -  Primary:

             -  To evaluate the progression-free survival of locoregionally advanced (stages
                III/IV) SCCHN patients undergoing postoperative chemoradiotherapy with panitumumab.

        -  Secondary:

             -  To evaluate the overall survival, event-free survival, and toxicities.

             -  To correlate efficacy parameters with 1) EGFR and downstream pathway activation, 2)
                FcyR polymorphisms, and 3) serum cytokine profiles. More specifically, the aim is
                to demonstrate the usefulness of biomarkers (downstream signaling molecules, FcyR
                polymorphisms, or tumor and serum cytokine(s) in predicting progression-free
                survival in patients with SCCHN treated with the above treatment. Specific
                biomarkers that relate to Epidermal Growth Factor Receptor and angiogenesis,
                including EGFR, pEGFR, Src, pMAPK, pSTAT3, pSTAT5, pSTAT1, pAKT, p38, p21, p27,
                PARP, E-cadherin, p-ErbB3, Ki67, VEGF, and IL-8, using reverse phase protein
                microarrays (RPPA) will be tested in baseline archival paraffin-embedded tumor
                tissue. To collect tumor tissue from pretreatment biopsies for cytokine/chemokine
                and immune biomarker studies on tumor tissue. We plan to investigate the expression
                of pAKT, pMAPK, and other EGFR pathway-related markers as well angiogenesis
                biomarkers. In addition, EGFR polymorphisms will be studied in tumor tissue samples
                and serum. Additional studies may be performed in the future. Some of these studies
                may be performed by Amgen.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Pathologically staged squamous cell carcinoma of the head and neck, stage III or IVa
             (AJCC 6th edition 2002) of the oral cavity, larynx, or hypopharynx that is status post
             potentially curative surgical resection without gross residual tumor, except the
             following: a)T3N0 laryngeal primary and b) any T1N1, if there are no high-risk
             pathologic features (high risk defined as positive margins, extracapsular spread, and
             perineural or angiolymphatic invasion).

          -  Patients should not have gross residual disease.

          -  No prior chemotherapy, biologic/targeted therapy (including any prior therapy which
             specifically and directly targets the EGFR pathway), or radiotherapy for head and neck
             cancer. A brief course, up to 2 weeks, of prior neoadjuvant single-agent
             biologic/targeted therapy of any type (except EGFR monoclonal antibodies) prior to
             surgical resection is permitted.

          -  No more than 6 7 weeks (minimum of 3 weeks) should have elapsed between surgery and
             initiation of radiation.

          -  No prior radiation or chemotherapy for head and neck cancer.

          -  ECOG performance status of 0-1

          -  Patients must have normal organ and marrow function Absolute neutrophil count
             >/=1,500/uL Platelets >/=100,000/uL Hemoglobin >/= 10 g/dL Total bilirubin <1.5 x
             normal institutional limits Creatinine clearance > 60 mL/min

          -  No prior invasive malignancy unless the DFS is 3 years or more.

          -  Age > 18 years.

          -  Pregnant or breast-feeding women are excluded (see exclusion criteria).

          -  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.

          -  Patients who have tumor tissue available from previous diagnostic or therapeutic
             procedures should submit the specimen for assessment of EGFR and related biomarkers
             after signing informed consent.

        Exclusion Criteria:

          -  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, recent myocardial infarction (within prior
             6 months), uncontrolled congestive heart failure, and cardiomyopathy with decreased
             ejection fraction. All patients will have a baseline EKG. If abnormalities consistent
             with active coronary artery disease are detected, the patient will be referred to a
             cardiologist for appropriate evaluation and management prior to treatment on study..
             Patients with history of hypertension must be well-controlled upon study entry
             (≤150/90) on a stable regimen of anti-hypertensive therapy. Patients should not have
             any prior history of hypertensive crisis or hypertensive encephalopathy.

          -  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, or malignancy that has been
             treated with a curative intent with a 3-year disease-free survival.

          -  No patients with significant baseline sensory or motor neurologic deficits(> grade I
             neuropathy) will be treated on this study.

          -  Pregnant women are excluded from this study because chemotherapy and radiation therapy
             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 chemotherapy, breastfeeding should be discontinued if the
             mother is treated with chemotherapy.

          -  Prior to study enrollment, women of childbearing potential (WOCBP) must be advised of
             the importance of avoiding pregnancy during trial participation and the potential risk
             factors for an unintentional pregnancy. In addition, men enrolled on this study should
             understand the risks to any sexual partner of childbearing potential and should
             practice an effective method of birth control.

          -  All WOCBP MUST have a negative urine pregnancy test at baseline, or within 7 days
             prior to receiving investigational product. The minimum sensitivity of the pregnancy
             test must be 25 IU/L or equivalent units of HCG. If the urine pregnancy test is
             positive, a serum pregnancy test will then be performed to confirm the result. In the
             event that both the urine and serum pregnancy tests are positive, the subject must not
             receive investigational product and must not be enrolled in the study.

          -  In addition, all WOCBP should be instructed to contact the Investigator immediately if
             they suspect they might be pregnant (e.g., missed or late menstrual period) at any
             time during study participation.

        The Investigator must immediately notify Amgen in the event of a confirmed pregnancy in a
        patient participating in the study.

        -Prior severe infusion reaction to a human monoclonal antibody.