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

Nausea and Vomiting Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00895245
• Other study ID #: 6862
• Secondary ID: NCI-2009-01669
• Status: Terminated
• Phase: Phase 2
• First received: May 7, 2009
• Last updated: May 7, 2013
• Start date: February 2009

Study information

• Verified date: May 2013
• Source: University of Washington
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 6
• Est. primary completion date: September 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Supportive Care

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Laryngeal Neoplasms
• Nasopharyngeal Neoplasms
• Nausea
• Nausea and Vomiting
• Oropharyngeal Neoplasms
• 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
• Vomiting

Intervention

Drug:
• fosaprepitant dimeglumine
Given IV
• cisplatin
Given IV
• palonosetron hydrochloride
Given IV
• dexamethasone
Given IV and orally

Other:
• questionnaire administration
Ancillary studies

Procedure:
• quality-of-life assessment
Ancillary studies

Radiation:
• 3-dimensional conformal radiation therapy
Undergo radiotherapy
• intensity-modulated radiation therapy
Undergo radiotherapy

Locations

Country	Name	City	State
United States	Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
University of Washington	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of patients with a complete response to the anti-emetic medication regimen		Up to day 27	No
Secondary	Rate of complete response to anti-emetic therapy in the delayed setting (25-120 hours after cisplatin infusion)		Up to day 27	No
Secondary	Control of nausea for 120 hours following each cisplatin infusion for multiple cycles of therapy as measured by the visual analog scale		Up to 7 weeks	No
Secondary	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		Up to 7 weeks	No