Clinical trial NCT01736917: Fosaprepitant + 5HT3 Receptor Antagonists + Dexamethasone in Germ Cell Tumors
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chemotherapy-Induced Nausea and Vomiting
Keywords: Fosaprepitant
5HT3 Receptor Antagonists
Dexamethasone
Germ Cell Tumors
Testis Cancer
Rescue Medications
Lead sponsor: Hoosier Cancer Research Network
Sponsor class: OTHER
Collaborators: name: Hoosier Cancer Research Network
name: Merck Sharp & Dohme LLC
First posted: 2012-11-29
Enrollment: 65
Sex: MALE
Minimum age (years): 15
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

Eligibility 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.

Primary outcomes:
measure: Percentage of Participants With Complete Response of Acute and Delayed Chemotherapy Induced Nausea and Vomiting
timeFrame: Days 1-8 of chemotherapy regimen
Secondary outcomes:
measure: Total Number of Emetic Episodes
timeFrame: Days 1-8 of chemotherapy regimen
measure: Use of Rescue Medications.
timeFrame: Days 1-8 of chemotherapy regimen
measure: Self-Reported Assessment of Nausea
timeFrame: Days 1-8 of chemotherapy regimen
Other outcomes:
Locations:
city: Indianapolis
country: United States
facility: Indiana University Melvin and Bren Simon Cancer Center
state: Indiana
city: St. Louis
country: United States
facility: Siteman Cancer Center
state: Missouri
city: Omaha
country: United States
facility: Nebraska Cancer Specialists
state: Nebraska
city: Charleston
country: United States
facility: MUSC Hollings Cancer Center
state: South Carolina
Study officials:
affiliation: Hoosier Cancer Research Network
name: Lawrence Einhorn, M.D.
role: STUDY_CHAIR
References:
citation: 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)
citation: 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)
citation: 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.