Trial record 1 of 1 for:    NCT01736917
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Fosaprepitant + 5HT3 Receptor Antagonists + Dexamethasone in Germ Cell Tumors

This study has been completed.
Sponsor:
Collaborators:
Hoosier Cancer Research Network
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Lawrence Einhorn, Hoosier Cancer Research Network
ClinicalTrials.gov Identifier:
NCT01736917
First received: November 21, 2012
Last updated: July 23, 2015
Last verified: July 2015
  Purpose

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.


Condition Intervention Phase
Chemotherapy-Induced Nausea and Vomiting
Drug: Fosaprepitant
Drug: Dexamethasone
Drug: 5HT3
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Hoosier Cancer Research Network:

Primary Outcome Measures:
  • Determine the Complete Response (CR) Rate of No Emetic Episodes or Use of Rescue Medications [ Time Frame: 1 month ] [ Designated as safety issue: No ]
    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


Secondary Outcome Measures:
  • Measure the Incidence of Vomiting or Retching [ Time Frame: 1 month ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
    This will determine the safety and toxicity of the treatment regimen utilizing CTCAE V4.0


Enrollment: 64
Study Start Date: January 2013
Study Completion Date: June 2015
Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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/m2 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
  Eligibility

Ages Eligible for Study:   15 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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.
  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: NCT01736917

Locations
United States, Indiana
Indiana University Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, United States, 46202
United States, Missouri
Siteman Cancer Center
St. Louis, Missouri, United States, 63110
United States, Nebraska
Nebraska Cancer Specialists
Omaha, Nebraska, United States, 68114
United States, South Carolina
MUSC Hollings Cancer Center
Charleston, South Carolina, United States, 29425
Sponsors and Collaborators
Lawrence Einhorn
Hoosier Cancer Research Network
Merck Sharp & Dohme Corp.
Investigators
Study Chair: Lawrence Einhorn, M.D. Hoosier Cancer Research Network
  More Information

Additional Information:
Publications:
Brames MJ, Case-Eads S, Hanna NH, Fausel CA, Breen T, Einhorn LH. Phase II study of fosaprepitant +5HT3 receptor antagonist + dexamethasone in patients with germ cell tumors undergoing 5-day cisplatin-based chemotherapy: A Hoosier Cancer Research Network Study. J Clin Oncol 33:5s, 2015 (suppl; abstr e20737)
Costantine Albany, Nasser H. Hanna, Joel Picus, Ralph J. Hauke, Christopher A. Fausel, Ziyue Liu, Mary J. Brames, Lawrence H. Einhorn. Phase II study of fosaprepitant plus 5HT3 receptor antagonists plus dexamethasone in patients with germ cell tumors undergoing 5-day cisplatin-based chemotherapy: Hoosier Oncology Group QL12-153. J Clin Oncol 32:5s, 2014 (suppl; abstr TPS4594)

Responsible Party: Lawrence Einhorn, Sponsor-Investigator, Hoosier Cancer Research Network
ClinicalTrials.gov Identifier: NCT01736917     History of Changes
Other Study ID Numbers: QL12-153
Study First Received: November 21, 2012
Last Updated: July 23, 2015
Health Authority: United States: Institutional Review Board

Keywords provided by Hoosier Cancer Research Network:
Fosaprepitant
5HT3 Receptor Antagonists
Dexamethasone
Germ Cell Tumors
Testis Cancer
Rescue Medications

Additional relevant MeSH terms:
Aprepitant
BB 1101
Dexamethasone
Dexamethasone 21-phosphate
Dexamethasone acetate
Fosaprepitant
Anti-Inflammatory Agents
Antiemetics
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Autonomic Agents
Central Nervous System Agents
Enzyme Inhibitors
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Molecular Mechanisms of Pharmacological Action
Neurokinin-1 Receptor Antagonists
Neurotransmitter Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Protease Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on August 27, 2015