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

Lawrence Einhorn

Status and phase: Completed; Phase 2

Conditions: Chemotherapy-Induced Nausea and Vomiting

Treatments: Drug: Fosaprepitant; Drug: Dexamethasone; Drug: 5HT3

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT01736917

QL12-153

Details and patient eligibility

About

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.

Full 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

Enrollment: 65 patients

Sex: Male

Ages: 15+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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65 participants in 1 patient group

Fosaprepitant + 5HT3 Receptor Antagonists + Dexamethasone

Experimental group

Description:

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

Treatment:

Drug: 5HT3

Drug: Dexamethasone

Drug: Fosaprepitant