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

Chemotherapy-Induced Nausea and Vomiting Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01736917
• Other study ID #: QL12-153
• Status: Completed
• Phase: Phase 2
• First received: November 21, 2012
• Last updated: July 23, 2015
• Start date: January 2013
• Est. completion date: June 2015

Study information

• Verified date: July 2015
• Source: Hoosier Cancer Research Network
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 64
• Est. completion date: June 2015
• Est. primary completion date: March 2015
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 15 Years and older

Eligibility

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.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chemotherapy-Induced Nausea and Vomiting

Intervention

Drug:
• Fosaprepitant
Fosaprepitant 150mg IV D3 for acute prophylaxis Fosaprepitant 150mg IV on Day 5 for delayed prophylaxis
• Dexamethasone
Dexamethasone 20mg PO daily on D1 and 2 for acute prophylaxis Dexamethasone 4mg PO BID on Days 6 through 8
• 5HT3
Any 5HT3RA on D1-5; D1, 3 and 5 if palonosetron is used.

Locations

Country	Name	City	State
United States	MUSC Hollings Cancer Center	Charleston	South Carolina
United States	Indiana University Melvin and Bren Simon Cancer Center	Indianapolis	Indiana
United States	Nebraska Cancer Specialists	Omaha	Nebraska
United States	Siteman Cancer Center	St. Louis	Missouri

Sponsors (3)

Lead Sponsor	Collaborator
Lawrence Einhorn	Hoosier Cancer Research Network, Merck Sharp & Dohme Corp.

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 Feb 2. [Epub ahead of print] — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determine the Complete Response (CR) Rate of No Emetic Episodes or Use of Rescue Medications	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	1 month	No
Secondary	Measure the Incidence of Vomiting or Retching	This will measure the incidence of vomiting or retching via patient log Days 1-8.	1 month	No
Secondary	Describe Detailed Use of Rescue Medications.	This will describe the detailed use of rescue medications for patients via patient log.	1 month	No
Secondary	Describe the Patient's Self-Reported Assessment of Nausea	This will describe the patient's self-reported assessment of nausea Days 1-8 using a 0-100mm visual analog scale (VAS).	1 month	No
Secondary	Determine the Number of Participants with Adverse Events as a Measure of Safety and Tolerability	This will determine the safety and toxicity of the treatment regimen utilizing CTCAE V4.0	1 month	Yes

External Links

•   Hoosier Cancer Research Network Website