Fosaprepitant Dimeglumine and Granisetron Transdermal System in Preventing Nausea and Vomiting in Patients With Breast Cancer Undergoing Chemotherapy

A Pilot Study to Evaluate the Efficacy of Fosaprepitant and Granisetron Transdermal System for the Prevention of Acute and Delayed Nausea and Vomiting in Breast Cancer Patients and to Identify Predictors of Response

This clinical trial studies how well fosaprepitant dimeglumine and granisetron transdermal system work in preventing nausea and vomiting in patients with breast cancer undergoing chemotherapy. Antiemetic drugs may help lessen or prevent nausea and vomiting in patients treated with chemotherapy

Study Overview

• Status: Terminated
• Conditions: Breast Cancer; Nausea; Vomiting
• Intervention / Treatment: Other: laboratory biomarker analysis; Drug: fosaprepitant dimeglumine; Drug: granisetron transdermal system

Detailed Description

PRIMARY OBJECTIVE:

I. To evaluate the efficacy of the combination of fosaprepitant (fosaprepitant dimeglumine) and granisetron transdermal system in the prevention of acute and delayed chemotherapy induced nausea and vomiting in breast cancer patients undergoing adjuvant or neoadjuvant chemotherapy.

SECONDARY OBJECTIVE:

I. To evaluate the safety of the combination of fosaprepitant and granisetron transdermal system in breast cancer patients undergoing adjuvan or neoadjuvant chemotherapy.

EXPLORATORY OBJECTIVE:

I. To explore the use of single nucleotide polymorphisms (SNPs) in the 5âhydroxytryptamine-3 (5HT3) and neurokinin-1 (NK-1) receptors as potential markers of efficacy.

OUTLINE: Patients receive granisetron transdermal system patch 24-48 hrs before the initiation of chemotherapy. Patients wear the granisetron transdermal system patch for 7 days. Patients receive fosaprepitant dimeglumine intravenously (IV) over 15 minutes on day 1 of chemotherapy. Treatment repeats every 2 or 3 weeks for up to 4 courses in the absence of unacceptable toxicity.

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90033
      • USC Norris Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with histologically confirmed breast cancer scheduled to receive chemotherapy with doxorubicin and cyclophosphamide (adjuvant or neoadjuvant)
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• Projected life expectancy of at least 3 months
• Provision of informed consent prior to any study-related procedures
• Negative pregnancy test for women of childbearing potential
• Absolute neutrophil count (ANC) >= 1500/mm^3
• Platelet count >= 100,000 cells/mm^3
• Hemoglobin >= 9.0g/dL
• Serum creatinine =< 1.5 mg/dl
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =< 2.5 X upper limit of normal (ULN)
• Alkaline phosphatase =< 2.5 X upper limit of normal; in patients with bone metastasis and no evidence of liver metastasis and bilirubin =< upper limit of normal an alkaline phosphatase =< 5 ULN will be allowed
• Serum bilirubin =< 1.0 mg/dL
• No other concomitant therapy directed at the cancer is allowed

Exclusion Criteria:

• Allergy or intolerance to 5HT3 or NK-1 antagonists and dexamethasone
• Use of another antiemetic agent (5HT3 antagonists, phenothiazines, butyrophenones, cannabinoids, metoclopramide, or corticosteroids) within 72 hours prior to day 1 of the study
• Use of anticoagulant agent (Warfarin, Coumadin, Jantoven, Marevan, Lawarin, Waran, or Warfant)
• An episode of vomiting or retching within 24 hours before the start of the initial treatment with chemotherapy
• Severe concurrent illness other than neoplasia
• Gastrointestinal obstruction or an active peptic ulcer
• Patients who are pregnant or breast feeding because aprepitant may be harmful to the developing fetus and newborn

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Supportive care (antiemetics); Patients receive granisetron transdermal system patch 24-48 hrs before the initiation of chemotherapy. Patients wear the granisetron transdermal system patch for 7 days. Patients receive fosaprepitant dimeglumine IV over 15 minutes on day 1 of chemotherapy. Treatment repeats every 2 or 3 weeks for up to 4 courses in the absence of unacceptable toxicity.

Other: laboratory biomarker analysis; Correlative studies; Drug: fosaprepitant dimeglumine; Given IV; Drug: granisetron transdermal system; Given granisetron transdermal system patch; Other Names: Sancuso; granisetron transdermal patch

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients with complete response, defined as no emesis and no use of rescue medication in acute phase (within first 24 hours of treatment)	The complete response rate with the exact 95% confidence intervals (CIs) will be calculated. The associations between the complete response rate and patient characteristics and biomarkers will be examined using Fisherâs exact test or Mann-Whitney U test whenever appropriate.	Within the first 24 hours of treatment
Proportion of patients with complete response, defined as no emesis and no use of rescue medication in delayed phase (within 2-4 days of treatment)	The complete response rate with the exact 95% CIs will be calculated. The associations between the complete response rate and patient characteristics and biomarkers will be examined using Fisherâs exact test or Mann-Whitney U test whenever appropriate.	Up to day 4

Collaborators and Investigators

• Sponsor: University of Southern California
• Collaborators: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start (Actual): September 4, 2012
• Primary Completion (Actual): May 22, 2017
• Study Completion (Actual): September 30, 2017

Study Registration Dates

• First Submitted: July 20, 2012
• First Submitted That Met QC Criteria: July 20, 2012
• First Posted (Estimate): July 25, 2012

Study Record Updates

• Last Update Posted (Actual): November 17, 2017
• Last Update Submitted That Met QC Criteria: November 15, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Signs and Symptoms, Digestive; Breast Diseases; Breast Neoplasms; Nausea; Vomiting; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Antiemetics; Gastrointestinal Agents; Serotonin Agents; Serotonin Antagonists; Neurokinin-1 Receptor Antagonists; Granisetron; Aprepitant; Fosaprepitant
• Other Study ID Numbers: 1B-11-5; NCI-2012-01170 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes