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

Study Overview
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Brief Summary
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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
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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

Official Title
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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

Conditions
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Chemotherapy-Induced Nausea and Vomiting

Intervention / Treatment
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* Drug: Fosaprepitant
* Drug: Dexamethasone
* Drug: 5HT3


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 15 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fosaprepitant + 5HT3 Receptor Antagonists + Dexamethasone<br>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<br>* Fosaprepitant 150mg IV D3 for acute prophylaxis Fosaprepitant 150mg IV on Day 5 for delayed prophylaxis<br>Drug: Dexamethasone<br>* Dexamethasone 20mg PO daily on D1 and 2 for acute prophylaxis Dexamethasone 4mg PO BID on Days 6 through 8<br>Drug: 5HT3<br>* Any 5HT3RA on D1-5; D1, 3 and 5 if palonosetron is used.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Complete Response of Acute and Delayed Chemotherapy Induced Nausea and Vomiting | 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 | total number of emetic episodes | Days 1-8 of chemotherapy regimen | 
| Use of Rescue Medications. | Total number of patients who received rescue medications. | Days 1-8 of chemotherapy regimen | 
| Self-Reported Assessment of Nausea | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fosaprepitant, 5HT3 Receptor Antagonists, Dexamethasone, Germ Cell Tumors, Testis Cancer, Rescue Medications