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

• 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: Lawrence Einhorn
• Collaborators: Hoosier Cancer Research Network; Merck Sharp & Dohme Corp.
• Information provided by (Responsible Party): Lawrence Einhorn, Hoosier Cancer Research Network

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Chemotherapy-Induced Nausea and Vomiting	Drug: Fosaprepitant; Drug: Dexamethasone; Drug: 5HT3	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 65 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (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
• Study Start Date: January 2013
• Actual Primary Completion Date: March 2015
• Actual Study Completion Date: June 2015

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. 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

Secondary Outcome Measures :

1. Total Number of Emetic Episodes [ Time Frame: Days 1-8 of chemotherapy regimen ]
   total number of emetic episodes
2. Use of Rescue Medications. [ Time Frame: Days 1-8 of chemotherapy regimen ]
   Total number of patients who received rescue medications.
3. 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.

Eligibility Criteria

• Ages Eligible for Study: 15 Years and older (Child, Adult, Older Adult)
• Sexes 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

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:

Hoosier Cancer Research Network Website 

Publications of Results:

Adra N, Albany C, Brames MJ, Case-Eads S, Johnson CS, Liu Z, Fausel CA, Breen T, Hanna NH, Hauke RJ, Picus J, 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. Support Care Cancer. 2016 Jul;24(7):2837-42. doi: 10.1007/s00520-016-3100-y. Epub 2016 Feb 2.

Other Publications:

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
• Other Study ID Numbers: QL12-153
• First Posted: November 29, 2012
• Results First Posted: May 25, 2016
• Last Update Posted: May 25, 2016
• Last Verified: April 2016

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Lawrence Einhorn, Hoosier Cancer Research Network:

Fosaprepitant; 5HT3 Receptor Antagonists; Dexamethasone; Germ Cell Tumors; Testis Cancer; Rescue Medications

Additional relevant MeSH terms:

Neoplasms, Germ Cell and Embryonal; Vomiting; Signs and Symptoms, Digestive; Neoplasms by Histologic Type; Neoplasms; Dexamethasone; Fosaprepitant; Aprepitant; Anti-Inflammatory Agents; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents; Neurokinin-1 Receptor Antagonists; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action