Clinical trial NCT00895245: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: 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
Lead sponsor: University of Washington
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2009-05-08
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: SUPPORTIVE_CARE

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Proportion of Patients With a Complete Response to the Anti-emetic Medication Regimen
timeFrame: 120 hours following cisplatin infusion
Secondary outcomes:
measure: Rate of Complete Response to Anti-emetic Therapy in the Delayed Setting (25-120 Hours After Cisplatin Infusion)
timeFrame: 25-120 hours following cisplatin infusion
measure: Control of Nausea for 120 Hours Following Each Cisplatin Infusion for Multiple Cycles of Therapy as Measured by the Visual Analog Scale
timeFrame: 120 hours following cisplatin infusion
measure: 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
timeFrame: 5 days following cisplatin infusion
Other outcomes:
Locations:
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
state: Washington
Study officials:
affiliation: Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
name: Keith Eaton
role: PRINCIPAL_INVESTIGATOR
References: