A Randomized Phase 2 Pharmacokinetic Trial of Chemotherapy With or Without Panitumumab in Patients With Metastatic and/or Recurrent Squamous Cell Carcinoma of the Head and Neck
Condition: Squamous Cell Carcinoma of Head and Neck
MeSH terms: Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck
Intervention: Panitumumab; Cisplatin; 5FU
Intervention description: This is a PK study comparing Panitumumab plus Chemotherapy to Chemotherapy alone; This is a PK study comparing Panitumumab plus Chemotherapy to Chemotherapy alone; This is a PK study comparing Panitumumab plus Chemotherapy to Chemotherapy alone
Intervention MeSH terms: Panitumumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 67.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: PK Study, Metastatic Recurrent

Summary:

      Study 20080008 was a PK sub-study to study 20050251[Japan 20050251A]. This PK protocol was
      amended 20-March-2009 and is now a Phase 2 stand alone study. There are no sites
      participating in the U.S.

      This study is designed to estimate the effect of panitumumab on the PK of cisplatin and 5-FU
      in subjects receiving cisplatin and 5-FU with or without panitumumab.

      To maximize any potential effect of panitumumab on the PK of cisplatin and 5-FU, the
      collection of PK samples of cisplatin and 5-FU will be taken during cycle 2 of the study, the
      point at which the PK of panitumumab is expected to be at steady-state after a dose of 9
      mg/kg given every 3 weeks.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically or cytologically confirmed squamous cell carcinoma of the head and neck
             (SCCHN) or its variants (eg, basaloid squamous cell carcinoma and adenosquamous cell
             carcinoma) of the oral cavity, oropharynx, hypopharynx, or larynx

          -  Diagnosis of metastatic disease and/or recurrent disease following locoregional
             therapy and determined to be incurable by surgery or radiotherapy

          -  Subjects who have received radiation as primary therapy are eligible if locoregional
             recurrence is in the field of radiation and has occurred ≥6 months after the
             completion of radiation therapy. Subjects whose locoregional recurrence is solely
             outside the field of radiation are eligible if the recurrence has occurred ≥ 3 months
             after the completion of radiation therapy.

          -  Measurable or non measurable disease. Target lesions must not be chosen from a
             previously irradiated field unless there has been radiographically and/or
             pathologically documented tumor progression in that lesion prior to randomization.

          -  Eastern cooperative oncology group (ECOG) performance status of 0 or 1

          -  Man or woman ≥ 18 years of age

          -  Hematological function, as follows (≤ 10 days prior to randomization):

        Absolute neutrophil count (ANC) ≥1.5 x 109/L Platelet count ≥ 100 x 109/L Hemoglobin ≥ 9
        g/dL - Renal function, as follows (≤ 10 days prior to randomization):

        Creatinine clearance (CrCl) ≥ 50 mL/min calculated by the Cockcroft Gault method as
        follows:

        Male creatinine clearance = (140 age) x (weight in Kg) / (serum Cr x 72) Female creatinine
        clearance = (140 age) x (weight in Kg) x 0.85 / (serum Cr x 72)

        - Hepatic function, as follows (≤ 10 days prior to randomization): Aspartate
        aminotransferase (AST) ≤ 3 x upper limit of normal (ULN) (≤ 5 x ULN if liver metastases)
        Alanine aminotransferase (ALT) ≤ 3 x ULN (≤ 5 x ULN if liver metastases) Total bilirubin ≤
        1.5 x ULN

        - Electrolytes, as follows (≤ 10 days prior to randomization): Magnesium ≥ lower limit of
        normal (LLN)

        - Negative pregnancy test ≤ 72 hours prior to randomization (females of childbearing
        potential only)

        Exclusion Criteria:

          -  Documented or symptomatic central nervous system metastases

          -  History of another primary cancer, except:

        Curatively treated in situ cervical cancer, or Curatively resected non melanoma skin
        cancer, or Other primary solid tumor curatively treated with no known active disease
        present and no treatment administered for ≥ 2 years prior to randomization

          -  Subjects whose only site of metastatic disease is a single spiculated lung nodule are
             assumed to have a second lung primary and are excluded unless there is unequivocal
             pathological confirmation of metastasis of the SCCHN primary

          -  Nasopharyngeal carcinoma

          -  Prior systemic treatment for metastatic and/or recurrent SCCHN Subjects with recurrent
             disease may have received re irradiation; however subjects who received chemotherapy
             concomitantly with re irradiation are excluded

          -  Prior systemic chemotherapy for SCCHN as part of the initial multimodality treatment
             for locally advanced disease if completed < 6 months prior to randomization

          -  Prior cisplatin containing induction chemotherapy followed by cisplatin containing
             chemoradiotherapy

          -  Prior anti EGFr antibody therapy (eg, cetuximab) or treatment with small molecule EGFr
             inhibitors (eg, gefitinib, erlotinib, lapatinib)

          -  Subjects requiring immunosuppressive agents (eg, methotrexate and cyclosporine),
             however corticosteroids are allowed

          -  Known allergy or hypersensitivity to any component of the study drugs

          -  Major surgery requiring general anesthesia and a significant incision (ie, larger than
             what is required for placement of central venous access, percutaneous feeding tube, or
             biopsy) ≤ 28 days or minor surgery (excluding central venous catheter placement,
             percutaneous feeding tube, and biopsy) ≤ 14 days prior to randomization. Subjects must
             have recovered from surgery related toxicities.

          -  Clinically significant cardiovascular disease (including myocardial infarction,
             unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac
             arrhythmia) ≤ 1 year prior to randomization

          -  History of interstitial lung disease eg, pneumonitis or pulmonary fibrosis or evidence
             of interstitial lung disease on baseline chest computerized tomography (CT) scan

          -  Symptomatic peripheral neuropathy grade ≥ 2 based on the Common Terminology Criteria
             for Adverse Events (CTCAE) v3.0

          -  Grade ≥ 3 hearing loss based on the CTCAE v3.0 Auditory/Ear (Hearing [without
             monitoring program])

          -  Subjects not recovered from all previous acute radiotherapy related toxicities

          -  Active infection requiring systemic treatment or any uncontrolled infection ≤ 14 days
             prior to randomization

          -  Known positive test for human immunodeficiency virus (HIV) infection, hepatitis C
             virus, chronic hepatitis B infection (testing is not required in the absence of
             clinical suspicion)

          -  Any co morbid condition that would increase risk of toxicity (eg, suspected or
             confirmed dihydropyrimidine deficiency)

          -  Other investigational procedures are excluded

          -  Subject currently is enrolled in or ≤ 30 days since ending other investigational
             device or drug study(s), or subject is receiving other investigational agents(s)

          -  Subject who is pregnant or breast feeding

          -  Man or woman of child bearing potential not consenting to use adequate contraceptive
             precautions ie, double barrier contraceptive methods (eg, diaphragm plus condom)
             during the course of the study and for 6 months after the last investigational
             product(s) administration for women, and 1 month for men

          -  Subject unwilling or unable to comply with study requirements

          -  Previously randomized into this study or Amgen study 20050251

          -  Subject has any kind of disorder that compromises the ability of the subject to give
             written informed consent and/or to comply with study procedures