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

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by University of Southern California
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Southern California
ClinicalTrials.gov Identifier:
NCT01649258
First received: July 20, 2012
Last updated: June 2, 2014
Last verified: June 2014
  Purpose

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


Condition Intervention
Breast Cancer
Nausea
Vomiting
Drug: granisetron transdermal system
Drug: fosaprepitant dimeglumine
Other: laboratory biomarker analysis

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Supportive Care
Official Title: 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

Resource links provided by NLM:


Further study details as provided by University of Southern California:

Primary Outcome Measures:
  • 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) [ Time Frame: Within the first 24 hours of treatment ] [ Designated as safety issue: No ]
    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.

  • 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) [ Time Frame: Up to day 4 ] [ Designated as safety issue: No ]
    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.

  • Proportion of patients with complete response, defined as no nausea, defined as Visual Analog Scale (VAS) less than 5 mm on a 0-100mm horizontal scale in acute phase (within 24 hours of treatment) [ Time Frame: Within the first 24 hours of treatment ] [ Designated as safety issue: No ]
    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.

  • Proportion of patients with complete response, defined as no nausea, defined as VAS less than 5 mm on a 0-100mm horizontal scale in delayed phase (within 2-4 days of treatment) [ Time Frame: Up to day 4 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Proportion of patients with partial response, defined as 2 or fewer episodes of emesis (Common Terminology Criteria for Adverse Events [CTCAE] version 4.0 grade 1-2), regardless of the use of rescue antiemetic medications (in acute and delayed phase) [ Time Frame: Up to day 4 ] [ Designated as safety issue: No ]
    Standard descriptive statistics will be used to display associations and test these associations (Fisherâs exact, Spearman correlations or the Kruskall-Walis test) between these measures of emesis and patient information, such as age, history of alcohol use, history of motion/morning sickness, stage of disease, treatment setting (neoadjuvant versus adjuvant), emesis experienced with prior exposure to chemotherapy, concomitant medication in detail, and whether or not rescue medications were used.

  • Proportion of patients with treatment failures, defined as more than 2 episodes of emesis (CTCAE version 4.0 grade 2 or greater), regardless of the use of rescue antiemetic medications [ Time Frame: Up to 12 weeks ] [ Designated as safety issue: No ]
    Standard descriptive statistics will be used to display associations and test these associations (Fisherâs exact, Spearman correlations or the Kruskall-Walis test) between these measures of emesis and patient information, such as age, history of alcohol use, history of motion/morning sickness, stage of disease, treatment setting (neoadjuvant versus adjuvant), emesis experienced with prior exposure to chemotherapy, concomitant medication in detail, and whether or not rescue medications were used.

  • Proportion of patients with partial response, defined as no significant nausea, defined as VAS less than 25 mm on a 0-100mm horizontal scale (in acute and delayed phase) [ Time Frame: Up to day 4 ] [ Designated as safety issue: No ]
    Standard descriptive statistics will be used to display associations and test these associations (Fisherâs exact, Spearman correlations or the Kruskall-Walis test) between these measures of emesis and patient information, such as age, history of alcohol use, history of motion/morning sickness, stage of disease, treatment setting (neoadjuvant versus adjuvant), emesis experienced with prior exposure to chemotherapy, concomitant medication in detail, and whether or not rescue medications were used.

  • Proportion of patients who developed nausea and vomiting in the first course of treatment out of all enrolled patients [ Time Frame: Up to 3 weeks ] [ Designated as safety issue: No ]
    Standard descriptive statistics will be used to display associations and test these associations (Fisherâs exact, Spearman correlations or the Kruskall-Walis test) between these measures of emesis and patient information, such as age, history of alcohol use, history of motion/morning sickness, stage of disease, treatment setting (neoadjuvant versus adjuvant), emesis experienced with prior exposure to chemotherapy, concomitant medication in detail, and whether or not rescue medications were used.

  • Proportion of patients who developed grade 1, 2, 3, or 4 nausea and vomiting with all courses of treatment out of all patients who developed nausea and vomiting [ Time Frame: Up to 12 weeks ] [ Designated as safety issue: No ]
    Standard descriptive statistics will be used to display associations and test these associations (Fisherâs exact, Spearman correlations or the Kruskall-Walis test) between these measures of emesis and patient information, such as age, history of alcohol use, history of motion/morning sickness, stage of disease, treatment setting (neoadjuvant versus adjuvant), emesis experienced with prior exposure to chemotherapy, concomitant medication in detail, and whether or not rescue medications were used.

  • Proportion of patients who developed nausea and vomiting on all courses [ Time Frame: Up to 12 weeks ] [ Designated as safety issue: No ]
    Standard descriptive statistics will be used to display associations and test these associations (Fisherâs exact, Spearman correlations or the Kruskall-Walis test) between these measures of emesis and patient information, such as age, history of alcohol use, history of motion/morning sickness, stage of disease, treatment setting (neoadjuvant versus adjuvant), emesis experienced with prior exposure to chemotherapy, concomitant medication in detail, and whether or not rescue medications were used.

  • Proportion of patients who experience grade 1, 2, 3, or 4 adverse events out of all patients who have received study drugs [ Time Frame: Up to 30 days after the last dose of study drug ] [ Designated as safety issue: No ]
    All toxicities will be summarized on an on-going basis. Standard descriptive statistics will be used to display associations and test these associations (Fisherâs exact, Spearman correlations or the Kruskall-Walis test) between these measures of emesis and patient information, such as age, history of alcohol use, history of motion/morning sickness, stage of disease, treatment setting (neoadjuvant versus adjuvant), emesis experienced with prior exposure to chemotherapy, concomitant medication in detail, and whether or not rescue medications were used.

  • Proportion of patients who missed 0, 1, or more than 2 doses of scheduled antiemetic medication at home on days 2 to 3, out of all patients [ Time Frame: Up to day 3 ] [ Designated as safety issue: No ]
    Standard descriptive statistics will be used to display associations and test these associations (Fisherâs exact, Spearman correlations or the Kruskall-Walis test) between these measures of emesis and patient information, such as age, history of alcohol use, history of motion/morning sickness, stage of disease, treatment setting (neoadjuvant versus adjuvant), emesis experienced with prior exposure to chemotherapy, concomitant medication in detail, and whether or not rescue medications were used.


Estimated Enrollment: 40
Study Start Date: September 2012
Estimated Study Completion Date: September 2016
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: granisetron transdermal system
Given granisetron transdermal system patch
Other Names:
  • granisetron transdermal patch
  • Sancuso
Drug: fosaprepitant dimeglumine
Given IV
Other: laboratory biomarker analysis
Correlative studies

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01649258

Locations
United States, California
USC Norris Comprehensive Cancer Center Recruiting
Los Angeles, California, United States, 90033
Contact: Agustin A. Garcia    323-865-0451    aagarcia@usc.edu   
Principal Investigator: Agustin A. Garcia         
Sponsors and Collaborators
University of Southern California
Investigators
Principal Investigator: Agustin Garcia University of Southern California
  More Information

No publications provided

Responsible Party: University of Southern California
ClinicalTrials.gov Identifier: NCT01649258     History of Changes
Other Study ID Numbers: 1B-11-5, NCI-2012-01170
Study First Received: July 20, 2012
Last Updated: June 2, 2014
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Granisetron
Breast Neoplasms
Nausea
Vomiting
Breast Diseases
Neoplasms
Neoplasms by Site
Signs and Symptoms
Signs and Symptoms, Digestive
Skin Diseases
Aprepitant
Fosaprepitant
Antiemetics
Autonomic Agents
Central Nervous System Agents
Gastrointestinal Agents
Molecular Mechanisms of Pharmacological Action
Neurokinin-1 Receptor Antagonists
Neurotransmitter Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Serotonin Agents
Serotonin Antagonists
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014