Pemetrexed and Oxaliplatin in Treating Patients With Locally Advanced Head and Neck Cancer
Condition: Head and Neck Cancer
MeSH terms: Head and Neck Neoplasms
Intervention: oxaliplatin; pemetrexed disodium
Intervention description: Group I: Patients receive pemetrexed disodium IV and oxaliplatin IV over 2 hours on day 1. Treatment repeats every 14 days for up to 4 courses. If patient progresses before receiving 4 courses of treatment, treatment will be discontinued and patient will proceed to surgery.
Group II: Patients receive treatment as in group I. If patient progresses before receiving 4 courses of treatment, treatment will be discontinued and patient will proceed to concurrent chemoradiotherapy.; Group I: Patients receive pemetrexed disodium IV and oxaliplatin IV over 2 hours on day 1. Treatment repeats every 14 days for up to 4 courses. If patient progresses before receiving 4 courses of treatment, treatment will be discontinued and patient will proceed to surgery.
Group II: Patients receive treatment as in group I. If patient progresses before receiving 4 courses of treatment, treatment will be discontinued and patient will proceed to concurrent chemoradiotherapy.
Intervention MeSH terms: Oxaliplatin; Pemetrexed
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 42.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: stage III squamous cell carcinoma of the hypopharynx; stage III squamous cell carcinoma of the larynx; stage III squamous cell carcinoma of the lip and oral cavity; stage III squamous cell carcinoma of the oropharynx; stage III squamous cell carcinoma of the paranasal sinus and nasal cavity; stage IV squamous cell carcinoma of the hypopharynx; stage IV squamous cell carcinoma of the larynx; stage IV squamous cell carcinoma of the lip and oral cavity; stage IV squamous cell carcinoma of the oropharynx; stage IV squamous cell carcinoma of the paranasal sinus and nasal cavity; untreated metastatic squamous neck cancer with occult primary

Summary:

      RATIONALE: Pemetrexed may stop the growth of tumor cells by blocking some of the enzymes
      needed for cell growth. Drugs used in chemotherapy, such as oxaliplatin, work in different
      ways to stop the growth of tumor cells, either by killing the cells or by stopping them from
      dividing. Giving pemetrexed together with oxaliplatin may kill more tumor cells.

      PURPOSE: This phase II trial is studying how well giving pemetrexed together with oxaliplatin
      works in treating patients with locally advanced head and neck cancer.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

        Inclusion criteria:

        Patients must meet all of the following criteria in order to be eligible for entry into the
        trial:

          -  Histologically or cytologically confirmed stage III - IVB HNSCC (includes unknown
             primary and ParaNasal Sinus cancers)but excludes nasopharyngeal, salivary gland or
             skin primaries (No TNM staging required)

          -  Patients must have a measurable disease defined by RECIST criteria

          -  Age > 18 years

          -  ECOG Performance Score of 0, 1 or 2

          -  Adequate bone marrow as evidenced by:

               -  Absolute neutrophil count > 1,500/μL

               -  Platelet count > 100,000/μL

          -  Adequate renal function as evidenced by serum creatinine < 1.5 mg/dL and CrCl > 45
             mL/min as determined by calculated creatinine clearance using the Cockroft-Gault
             formula:

               -  CrCl = (140-age) x (weight in kg)/72 x serum creatinine

               -  Multiply by 0.85 (85%) for females

          -  Adequate hepatic function as evidenced by:

               -  Serum total bilirubin < 1.5 mg/dL

               -  Alkaline phosphatase < 3X the ULN for the reference lab

               -  SGOT/SGPT < 3X the ULN for the reference lab

          -  Patients or their legal representatives must be able to read, understand and provide
             informed consent to participate in the trial.

          -  Patients of childbearing potential and their partners must agree to use an effective
             form of contraception during the study and for 90 days following the last dose of
             study medication (an effective form of contraception is an oral contraceptive, double
             barrier method or surgical intervention resulting in sterility).

          -  Patients must be able to interupt NSAIDs at 2 days before (5 days for long-acting
             NSAIDs),the day of, and 2 days following administration of Pemetrexed.

          -  Patients must be willing and able to take Folic Acid (350-1000 μg) daily beginning 1
             week (7 days) prior to the first dose of Pemetrexed and continued daily until 3 weeks
             after the last dose of study therapy. In addition, patients must be willing to
             maintain a Pill Diary as part of study compliance.

          -  Patients must be willing and able to take Vitamin B12 (1000 μg) administered
             intramuscularly beginning 1 week (7 days) prior to the first dose of Pemetrexed and
             repeated at the planned End of Treatment visit (no later than 9 weeks from the first
             injection).

          -  Patients must be willing and able to take Dexamethasone (4 mg of oral or equivalent)
             that should be given twice daily on the day before, the day of, and the day after each
             dose of Pemetrexed for rash prophylaxis unless medically contraindicated.

        Exclusion Criteria:

        A patient may not be enrolled in the trial if any of the following criteria are met:

          -  Patients with an active infection or with a fever > 101.30 F within 3 days of the
             first scheduled day of protocol treatment

          -  History of prior malignancy within the past 3 years except for curatively treated
             basal cell carcinoma of the skin, cervical intra-epithelial neoplasia, or localized
             prostate cancer with a current PSA of < 1.0 mg/dL on 2 successive evaluations, at
             least 3 months apart, with the most recent evaluation no more than 4 weeks prior to
             entry

          -  Patients with known hypersensitivity to any of the components of Oxaliplatin and
             Pemetrexed

          -  Patients who received any chemotherapy, radiation therapy or surgical resection other
             than diagnostic biopsies for HNSCC prior to the first scheduled day of protocol
             treatment

          -  Patients who are receiving concurrent investigational therapy or who have received
             investigational therapy within 30 days of the first scheduled day of protocol
             treatment(investigational therapy is defined as treatment for which there is currently
             no regulatory authority approved indication)

          -  Peripheral neuropathy ≥ Grade 2

          -  Patients who are pregnant or lactating

          -  Any other medical condition, including mental illness or substance abuse, deemed by
             the Investigator to be likely to interfere with a patient's ability to sign informed
             consent,cooperate and participate in the study, or interferes with the interpretation
             of the results.

          -  History of allogeneic transplant

          -  Known HIV (active, previously treated or both)

          -  Presence of clinically detectable (by physical exam) third-space fluid collections,
             for example, ascites or pleural effusions that cannot be controlled by drainage or
             other procedures prior to study entry.