Fosaprepitant + 5HT3 Receptor Antagonists + Dexamethasone in Germ Cell Tumors

April 18, 2016 updated by: Lawrence Einhorn

Phase II Study of Fosaprepitant + 5HT3 Receptor Antagonists + Dexamethasone in Patients With Germ Cell Tumors Undergoing 5 Day Cisplatin-based Chemotherapy: Hoosier Oncology Group Study QL12-153

The hypothesis is that the substitution of multi-day oral aprepitant with (intravenous) IV fosaprepitant, in combination with a 5-HT3 receptor antagonists (5HT3RA) + dexamethasone will provide comparable protection from 5 day cisplatin chemotherapy induced nausea and vomiting, compared to the results of our prior study of aprepitant. This study will be the first clinical trial evaluating fosaprepitant in patients receiving multi-day cisplatin. This will be a single arm, phase II study. The investigators propose to utilize intravenous (IV) fosaprepitant on days 3 and 5 of the 5-day cisplatin chemotherapy regimen. It is anticipated that fosaprepitant can suppress delayed chemo-induced nausea and vomiting for 2-5 days after therapy. This study will test the value of fosaprepitant in this patient population.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OUTLINE: This is a multi-center study.

Treatment Regimen:

Patients must have no nausea and/or vomiting for 24 hours and must not have used other anti-emetics for 72 hours prior to starting protocol treatment. Treatment must not start until this criteria is satisfied.

Any germ cell chemotherapy regimen utilizing cisplatin (20mg/m^2 x 5 days). This will usually be combined with bleomycin (BEP), etoposide (EP), ifosfamide (VIP), vinblastine (VeIP), paclitaxel (TIP) or epirubicin. All of these regimens get the identical cisplatin, which is the only highly emetic drug in any of the chemo regimens.

Acute emesis prophylaxis (administered per institutional standards prior to chemotherapy):

  • Any 5HT3 receptor antagonist may be used days 1 through 5 or days 1, 3 and 5 if palonosetron is used per institutional standards.
  • Dexamethasone 20mg PO (orally) daily, days 1 and 2
  • Fosaprepitant 150mg IV on day 3

Delayed emesis prophylaxis:

  • Fosaprepitant 150mg IV on day 5
  • Dexamethasone 4mg PO BID (twice a day) on days 6, 7 and 8

PRN (as needed) antiemetics allowed at the discretion of the treating investigator

  • No additional doses of 5HT3 receptor antagonist, dexamethasone, or fosaprepitant will be given during the acute or delayed treatment periods

ECOG Performance Status of 0-2

Life Expectancy: Not specified

Hematopoietic:

  • White blood cell count (WBC) > 3.0 K/mm3
  • Absolute neutrophil count ≥ 1.5 K/mm3
  • Hemoglobin (Hgb) > 10 g/dL
  • Platelets > 100 K/mm3

Hepatic:

  • Bilirubin < 1.5 x ULN (upper limit of normal)
  • Aspartate aminotransferase (AST, SGOT) ≤ 3 x ULN
  • Alanine aminotransferase (ALT, SGPT) ≤ 3 x ULN

Renal:

  • Creatinine ≤ 2 mg/dl

Study Type

Interventional

Enrollment (Actual)

65

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Indiana University Melvin and Bren Simon Cancer Center
    • Missouri
      • St. Louis, Missouri, United States, 63110
        • Siteman Cancer Center
    • Nebraska
      • Omaha, Nebraska, United States, 68114
        • Nebraska Cancer Specialists
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • MUSC Hollings Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

15 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  • Male patients ≥15 years of age with histologically or cytologically confirmed diagnosis of germ cell tumor receiving a standard 5 day cisplatin based chemotherapy regimen. Prior chemotherapy is allowed. Patients do not have to be chemo naïve.
  • Written informed consent and HIPAA authorization for release of personal health information.
  • Patients must have had no nausea or vomiting for 24 hours and no anti-emetic use for 72 hours prior to starting protocol therapy. Treatment must not start in registered patients until this criteria is met.

Exclusion Criteria:

  • No active central nervous system (CNS) metastases. Patients with neurological symptoms must undergo a head CT scan or brain MRI to exclude brain metastasis. NOTE: A patient with prior brain metastasis may be considered if they have completed their treatment for brain metastasis, no longer require corticosteroids, and are asymptomatic.
  • No prior malignancy is allowed except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, Gleason < grade 7 prostate cancers, or other cancer for which the patient has been disease-free for at least 1 year.
  • No previous treatment with any investigational agent within 30 days prior to registration for protocol therapy.
  • No concurrent participation in a clinical trial which involves another investigational agent.
  • No use of agents expected to induce the metabolism of fosaprepitant which include: rifampin, rifabutin, phenytoin, carbamazepine, and barbiturates.
  • No concurrent use of agents which may inhibit metabolism of fosaprepitant which include: cisapride, macrolide antibiotics (erythromycin, clarithromycin, azithromycin), azole antifungal agents (ketoconazole, itraconazole, voriconazole, fluconazole), amifostine, nelfinavir, calcium channel antagonists such as verapamil and diltiazem, and ritonavir.
  • No concurrent use of warfarin while on study.
  • No known history of anticipatory nausea or vomiting.
  • No clinically significant infections as judged by the treating investigator.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Fosaprepitant + 5HT3 Receptor Antagonists + Dexamethasone

Patients must have no nausea and/or vomiting for 24 hours and must not have used other anti-emetics for 72 hours prior to starting protocol treatment. Treatment must not start until this criteria is satisfied.

  • Any germ cell chemotherapy regimen utilizing Cisplatin (20mg/m2 x 5 days).

Acute emesis prophylaxis:

  • Any 5HT3 receptor antagonist may be used D1 - 5 or D1, 3 and 5 if palonosetron is used per institutional standards.
  • Dexamethasone 20mg PO (orally) daily, D1 and 2
  • Fosaprepitant 150mg IV on day 3

Delayed emesis prophylaxis:

  • Fosaprepitant 150mg IV on D5
  • Dexamethasone 4mg PO BID (twice a day) on D6, 7 and 8

PRN antiemetics allowed at the discretion of the treating investigator

  • No additional doses of 5HT3 receptor antagonist, dexamethasone, or fosaprepitant will be given during the acute or delayed treatment periods
Drug: Fosaprepitant
Fosaprepitant 150mg IV D3 for acute prophylaxis Fosaprepitant 150mg IV on Day 5 for delayed prophylaxis
Drug: Dexamethasone
Dexamethasone 20mg PO daily on D1 and 2 for acute prophylaxis Dexamethasone 4mg PO BID on Days 6 through 8
Drug: 5HT3
Any 5HT3RA on D1-5; D1, 3 and 5 if palonosetron is used.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants With Complete Response of Acute and Delayed Chemotherapy Induced Nausea and Vomiting
Time Frame: Days 1-8 of chemotherapy regimen
complete response (CR) of both acute (days 1 through 5) and delayed (days 6 through 8) CINV, defined by no emetic episodes or use of rescue medications
Days 1-8 of chemotherapy regimen

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Total Number of Emetic Episodes
Time Frame: Days 1-8 of chemotherapy regimen
total number of emetic episodes
Days 1-8 of chemotherapy regimen
Use of Rescue Medications.
Time Frame: Days 1-8 of chemotherapy regimen
Total number of patients who received rescue medications.
Days 1-8 of chemotherapy regimen
Self-Reported Assessment of Nausea
Time Frame: Days 1-8 of chemotherapy regimen

the patient's self-reported assessment of nausea Days 1-8 using a 0-100mm visual analog scale (VAS) median.

The Visual Analouge (VAS) 100mm Scale Score for Chemotherapy Induced Nausea and Vomiting (CINV). Participants were asked to mark a linear scale 100mm in length representing their level of nausea with 0mm indicating no nausea and 100mm indicating severe nausea. Median VAS scores (in mm) are reported, per day.
Days 1-8 of chemotherapy regimen

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Lawrence Einhorn

Collaborators

Merck Sharp & Dohme LLC
Hoosier Cancer Research Network

Investigators

  • Study Chair: Lawrence Einhorn, M.D., Hoosier Cancer Research Network

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2013

Primary Completion (Actual)

March 1, 2015

Study Completion (Actual)

June 1, 2015

Study Registration Dates

First Submitted

November 21, 2012

First Submitted That Met QC Criteria

November 26, 2012

First Posted (Estimate)

November 29, 2012

Study Record Updates

Last Update Posted (Estimate)

May 25, 2016

Last Update Submitted That Met QC Criteria

April 18, 2016

Last Verified

April 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • QL12-153

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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