Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01736917
Recruitment Status : Completed
First Posted : November 29, 2012
Results First Posted : May 25, 2016
Last Update Posted : May 25, 2016
Sponsor:
Collaborators:
Hoosier Cancer Research Network
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Lawrence Einhorn, Hoosier Cancer Research Network

Tracking Information
First Submitted Date  ICMJE November 21, 2012
First Posted Date  ICMJE November 29, 2012
Results First Submitted Date  ICMJE March 1, 2016
Results First Posted Date  ICMJE May 25, 2016
Last Update Posted Date May 25, 2016
Study Start Date  ICMJE January 2013
Actual Primary Completion Date March 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 18, 2016)
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
Original Primary Outcome Measures  ICMJE
 (submitted: November 26, 2012)
Determine the Complete Response (CR) Rate of No Emetic Episodes or Use of Rescue Medications [ Time Frame: 1 month ]
This will determine the Complete Response (CR) rate (no emetic episodes or use of rescue medications) in germ cell tumor patients treated with IV fosaprepitant in combination with a 5HT3RA plus dexamethasone during a 5 day cisplatin regimen
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 18, 2016)
  • Total Number of Emetic Episodes [ Time Frame: Days 1-8 of chemotherapy regimen ]
    total number of emetic episodes
  • Use of Rescue Medications. [ Time Frame: Days 1-8 of chemotherapy regimen ]
    Total number of patients who received rescue medications.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: November 26, 2012)
  • Measure the Incidence of Vomiting or Retching [ Time Frame: 1 month ]
    This will measure the incidence of vomiting or retching via patient log Days 1-8.
  • Describe Detailed Use of Rescue Medications. [ Time Frame: 1 month ]
    This will describe the detailed use of rescue medications for patients via patient log.
  • Describe the Patient's Self-Reported Assessment of Nausea [ Time Frame: 1 month ]
    This will describe the patient's self-reported assessment of nausea Days 1-8 using a 0-100mm visual analog scale (VAS).
  • Determine the Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: 1 month ]
    This will determine the safety and toxicity of the treatment regimen utilizing CTCAE V4.0
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Fosaprepitant + 5HT3 Receptor Antagonists + Dexamethasone in Germ Cell Tumors
Official Title  ICMJE 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
Brief Summary 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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Chemotherapy-Induced Nausea and Vomiting
Intervention  ICMJE
  • 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.
Study Arms  ICMJE 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
Interventions:
  • Drug: Fosaprepitant
  • Drug: Dexamethasone
  • Drug: 5HT3
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 18, 2016)
65
Original Estimated Enrollment  ICMJE
 (submitted: November 26, 2012)
64
Actual Study Completion Date  ICMJE June 2015
Actual Primary Completion Date March 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 15 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01736917
Other Study ID Numbers  ICMJE QL12-153
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Lawrence Einhorn, Hoosier Cancer Research Network
Study Sponsor  ICMJE Lawrence Einhorn
Collaborators  ICMJE
  • Hoosier Cancer Research Network
  • Merck Sharp & Dohme Corp.
Investigators  ICMJE
Study Chair: Lawrence Einhorn, M.D. Hoosier Cancer Research Network
PRS Account Hoosier Cancer Research Network
Verification Date April 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP