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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

Primary Purpose

Nausea and Vomiting, Stage III Squamous Cell Carcinoma of the Hypopharynx, Stage III Squamous Cell Carcinoma of the Larynx

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
fosaprepitant dimeglumine
cisplatin
palonosetron hydrochloride
dexamethasone
Functional Living Index-Emesis Questionnaire
Emesis Diary
Radiotherapy
Sponsored by
University of Washington
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional supportive care trial for Nausea and Vomiting

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Arm I

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Rate of Complete Response to Anti-emetic Therapy in the Delayed Setting (25-120 Hours After 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.
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.

Full Information

First Posted
May 7, 2009
Last Updated
April 13, 2017
Sponsor
University of Washington
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00895245
Brief Title
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

2. Study Status

Record Verification Date
April 2017
Overall Recruitment Status
Terminated
Why Stopped
Study stopped due to lack of efficacy in first 6 patients
Study Start Date
February 2009 (undefined)
Primary Completion Date
September 2010 (Actual)
Study Completion Date
February 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Washington
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Supportive Care
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
6 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm I
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
fosaprepitant dimeglumine
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
cisplatin
Other Intervention Name(s)
CACP, CDDP, CPDD, DDP, Neoplatin
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
palonosetron hydrochloride
Other Intervention Name(s)
Aloxi, RS 25259-197
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
dexamethasone
Other Intervention Name(s)
Aeroseb-Dex, Decaderm, Decadron, Decaspray, DM, DXM
Intervention Description
Given IV and orally
Intervention Type
Other
Intervention Name(s)
Functional Living Index-Emesis Questionnaire
Intervention Description
Ancillary studies
Intervention Type
Behavioral
Intervention Name(s)
Emesis Diary
Intervention Description
Ancillary studies
Intervention Type
Radiation
Intervention Name(s)
Radiotherapy
Other Intervention Name(s)
3-D conformal radiotherapy or IMRT
Intervention Description
Undergo radiotherapy
Primary Outcome Measure Information:
Title
Proportion of Patients With a Complete Response to the Anti-emetic Medication Regimen
Description
Complete response is defined as no emesis or rescue nausea medications needed in the first 120 hours following cisplatin infusion.
Time Frame
120 hours following cisplatin infusion
Secondary Outcome Measure Information:
Title
Rate of Complete Response to Anti-emetic Therapy in the Delayed Setting (25-120 Hours After Cisplatin Infusion)
Time Frame
25-120 hours following cisplatin infusion
Title
Control of Nausea for 120 Hours Following Each Cisplatin Infusion for Multiple Cycles of Therapy as Measured by the Visual Analog Scale
Description
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.
Time Frame
120 hours following cisplatin infusion
Title
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
Description
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.
Time Frame
5 days following cisplatin infusion

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Keith Eaton
Organizational Affiliation
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Official's Role
Principal Investigator
Facility Information:
Facility Name
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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