Fosaprepitant Dimeglumine, Palonosetron Hydrochloride, and Dexamethasone in Preventing Nausea and Vomiting Caused by Cisplatin in Patients With Stage III or Stage IV Head and Neck Cancer Undergoing Chemotherapy and Radiation Therapy

Study Overview
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Brief Summary
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RATIONALE: Fosaprepitant dimeglumine, palonosetron hydrochloride, and dexamethasone may help lessen or prevent nausea and vomiting caused by cisplatin in patients with head and neck cancer undergoing chemotherapy and radiation therapy. PURPOSE: This phase II trial is studying how well fosaprepitant dimeglumine together with palonosetron hydrochloride and dexamethasone works in preventing nausea and vomiting caused by cisplatin in patients with stage III or stage IV head and neck cancer undergoing chemotherapy and radiation therapy.

Detailed Description
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PRIMARY OBJECTIVES: I. To determine the complete response rate of anti-emetic therapy based on a single dose of intravenous fosaprepitant with multiple cycles of high dose cisplatin (complete response is defined as no emesis or rescue nausea medications needed in the 120 hours following cisplatin infusion). SECONDARY OBJECTIVES: I. To determine the complete response rate of anti-emetic therapy based on a single dose of intravenous fosaprepitant with multiple cycles of high dose cisplatin in the delayed period (25-120 hours following cisplatin infusion). II. To determine efficacy of anti-emetic therapy based on a single-dose of intravenous fosaprepitant to achieve adequate control of nausea following multiple cycles of high-dose cisplatin as defined by a score on the visual analog scale of < 25mm in the 120 hours following cisplatin infusion. III. To determine the functional impact of cisplatin induced nausea and vomiting (CINV) on daily life as measured by the Functional Living Index-Emesis (FLIE) Questionnaire total score. OUTLINE: Patients receive cisplatin IV on day 1. Treatment repeats every 21 days for up to 3 courses. Patients also undergo 3-D conformal radiotherapy or intensity-modulated radiotherapy once daily 5 days a week for up to 7 weeks. Patients receive fosaprepitant dimeglumine IV, palonosetron hydrochloride IV, and dexamethasone IV on day 1 (prior to cisplatin infusion). Patients then receive oral dexamethasone on days 2-4. Patients with no emesis or requirement for rescue anti-emetics in the first 120 hours after cisplatin infusion continue to receive the anti-emetic regimen as above with the second and third courses of cisplatin. Patients complete an emesis diary (that includes a nausea visual analog scale) daily for 5 days after each cisplatin infusion. Patients also complete a Functional Living Index-Emesis Questionnaire on day 8 of each course of chemotherapy.

Official Title
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A Phase II Clinical Trial Investigating the Efficacy of Single-Dose Fosaprepitant for the Prevention of Cisplatin-Induced Nausea and Vomiting (CINV) in Patients With Head & Neck Cancer Undergoing Concurrent Chemotherapy and Radiation

Conditions
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Nausea and Vomiting, 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 Nasopharynx, Stage III Squamous Cell Carcinoma of the Oropharynx, 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 Nasopharynx, Stage IV Squamous Cell Carcinoma of the Oropharynx

Intervention / Treatment
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* Drug: fosaprepitant dimeglumine
* Drug: cisplatin
* Drug: palonosetron hydrochloride
* Drug: dexamethasone
* Other: Functional Living Index-Emesis Questionnaire
* Behavioral: Emesis Diary
* Radiation: Radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Cytologically or pathologically documented squamous cell carcinoma of the oral cavity, oropharynx, larynx, hypopharynx, or nasopharynx Stage III or IV disease according to the AJCC Cancer Staging Handbook Sixth Edition Planned definitive or adjuvant radiation with concurrent cisplatin (100 mg/m2 every 3 weeks for three cycles) ECOG Performance Status of 0-2 Adequate Organ Function (Hepatic: bilirubin =< 1.5 x ULN; AST and ALT =< 3 x ULN; Renal: calculated creatinine clearance >= 55ml/min (using the Cockcroft-Gault Formula); Bone Marrow: platelet count >= 100 x 10^9/L; absolute neutrophil count >= 1.25 x 10^9/L) Signed Informed Consent Male and female patients with reproductive potential must use an acceptable contraceptive method (with double barrier protection for pre-menopausal women) Predicted life expectancy > 12 weeks Willingness to complete patient diary and questionnaires Exclusion Criteria: Inability or unwillingness to comply with radiotherapy or chemotherapy Use of illicit drugs or on-going alcohol use Vomiting within the 24 hours prior to cisplatin infusion Evidence of clinically significant congestive heart failure (Patients must be able to tolerate hydration with cisplatin) Peripheral Neuropathy > Grade 2 Significant hearing loss Pregnant or breast-feeding women Patients may be enrolled in additional clinical trials, as long as no additional investigational agents are being used Patients with a hypersensitivity to fosaprepitant, aprepitant, polysorbate, and any other components of the EMEND product The following therapies are excluded during the treatment phase of the study: investigational agents; anti-neoplastic or anti-tumor agents, including immunotherapy, and hormonal anti-cancer therapy; additional scheduled anti-emetic medications, unless needed as rescue medications for acute or delayed nausea/vomiting Strong Inhibitors of CYP3A4: ketoconazole, itraconazole, clarithromycin, ritonavir, and nelfinavir; strong Inducers of CYP3A4: rifampin, carbamazepine, and phenytoin

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Supportive Care
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>Patients receive cisplatin IV on day 1. Treatment repeats every 21 days for up to 3 courses. Patients also undergo radiotherapy once daily 5 days a week for up to 7 weeks. Patients receive fosaprepitant dimeglumine IV, palonosetron hydrochloride IV, and dexamethasone IV on day 1.Patients then receive oral dexamethasone on days 2-4. Patients with no emesis or requirement for rescue anti-emetics in the first 120 hours after cisplatin infusion continue to receive the anti-emetic regimen as above with the second and third courses of cisplatin. Patients complete an emesis diary daily for 5 days after each cisplatin infusion. Patients also complete a Functional Living Index-Emesis Questionnaire on day 8 after each cisplatin infusion. | Drug: fosaprepitant dimeglumine<br>* Given IV<br>Drug: cisplatin<br>* Given IV<br>* Other names: Neoplatin;Drug: palonosetron hydrochloride<br>* Given IV<br>* Other names: RS 25259-197;Drug: dexamethasone<br>* Given IV and orally<br>* Other names: DXM;Other: Functional Living Index-Emesis Questionnaire<br>* Ancillary studies<br>Behavioral: Emesis Diary<br>* Ancillary studies<br>Radiation: Radiotherapy<br>* Undergo radiotherapy<br>* Other names: 3-D conformal radiotherapy or IMRT;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Patients With a Complete Response to the Anti-emetic Medication Regimen | Complete response is defined as no emesis or rescue nausea medications needed in the first 120 hours following cisplatin infusion. | 120 hours following cisplatin infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Complete Response to Anti-emetic Therapy in the Delayed Setting (25-120 Hours After Cisplatin Infusion) |  | 25-120 hours following cisplatin infusion | 
| Control of Nausea for 120 Hours Following Each Cisplatin Infusion for Multiple Cycles of Therapy as Measured by the Visual Analog Scale | The visual analog scale ranges from 0-100. 0 is labeled as no nausea and 100 is labeled as nausea as bad as it could be A score of < 25 is considered to indicate no significant nausea. All patients discontinued trial after only one cisplatin infusion. | 120 hours following cisplatin infusion | 
| Impact of Cisplatin-induced Nausea and Vomiting on Daily Life During the 5 Day Period Following Cisplatin Infusion for Multiple Cycles as Measured by the Functional Living Index-Emesis Questionnaire | FLIE is a patient-completed quality of life assessment modified from the original Functional Living Index - Cancer questionnaire. FLIE contains two domains: nausea and vomiting with nine items in each domain. The first item asks the patient to rate how much nausea (or vomiting) has occurred over a 5 day period. The remaining eight items ask patients to rate the impact of nausea (or vomiting) on various aspects of a patient's life (for example, ability to enjoy meals/liquids). Each item is answered using a 7 point visual analog scale with 7 being none /not at all and 1 being a great deal. The two domains are summed for a total score with a possible range of 18-126. Higher scores indicate a more favorable quality of life. A total score of >108 defines those patients who had a minimal impact of CINV on quality of life. All particpants discontinued the trial after one cycle of cisplatin. | 5 days following cisplatin infusion |