Pemetrexed and Oxaliplatin in Treating Patients With Locally Advanced Head and Neck Cancer

Study Overview
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Brief Summary
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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.

Detailed Description
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OBJECTIVES: Primary To evaluate the clinical response rate in patients with locally advanced squamous cell carcinoma of the head and neck treated with neoadjuvant pemetrexed disodium and oxaliplatin. Secondary To evaluate the pathological complete response in patients who undergo surgical resection or post-induction biopsy. To assess toxicity of therapy, including the assessment of quality of life, fatigue, and head and neck cancer-related symptoms. To predict response and toxicities based on pharmacogenomics, genomics, and proteomics. OUTLINE: This is a nonrandomized, open-label study. Patients are assigned to 1 of 2 groups based on resectability of disease (resectable vs nonresectable). Group I (resectable disease): 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. After completion of pemetrexed disodium and oxaliplatin, patients undergo surgical resection of disease. Group II (nonresectable disease): 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. After completion of pemetrexed disodium and oxaliplatin, patients undergo concurrent chemoradiotherapy. Blood samples are collected at baseline and periodically during study for biomarker and pharmacokinetic studies. Quality of life is assessed prior to each course of therapy and at 4-6 weeks after the last course. After completion of study treatment, patients are followed periodically for up to 3 years.

Official Title
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Phase II Trial: Efficacy and Toxicity of Induction Pemetrexed (ALIMTA) and Oxaliplatin (ELOXATIN) in Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma

Conditions
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Head and Neck Cancer

Intervention / Treatment
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* Drug: oxaliplatin
* Drug: pemetrexed disodium


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: drug therapy<br> | Drug: oxaliplatin<br>* 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.<br>* Other names: Eloxatin;Drug: pemetrexed disodium<br>* 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.<br>* Other names: Alimta;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient Response to Treatment Measured by RECIST Criteria | RECIST response categories: Progressive disease (PD): >=20% increase in sum of longest diameter (LD) of target lesion(s), taking as reference smallest sum LD recorded since treatment started. Complete response (CR): disappearance of all target lesions. Partial response (PR): >=30% decrease in sum of LD of target lesion(s), taking as reference baseline sum LD. Stable disease (SD): neither sufficient shrinkage to qualify as PR nor sufficient increase to qualify as PD. | at 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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