Aprepitant + a 5HT3 + Dexamethasone in Patients With Germ Cell Tumors

Germ Cell Tumors Clinical Trial

Official title:

Phase III, Double-Blind, Placebo-Controlled, Crossover Study Evaluating Aprepitant in Combination With a 5HT3 & Dexamethasone in Patients With Germ Cell Tumors Undergoing 5 Day Cisplatin-Based Chemotherapy Regimen

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00572572
• Other study ID #: QL05-37
• Status: Completed
• Phase: Phase 3
• First received: December 11, 2007
• Last updated: November 19, 2012
• Start date: December 2007
• Est. completion date: February 2011

Study information

• Verified date: November 2012
• Source: Hoosier Cancer Research Network
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Aprepitant is currently approved for prophylaxis of acute and delayed CINV for highly emetogenic chemotherapy regimens, including cisplatin; however, it has not yet been studied in multiple-day chemotherapy treatment programs. This study will compare the addition of aprepitant compared to placebo administered on days 3,4,5 of chemotherapy administration for acute CINV prophylaxis with standard antiemetic prophylaxis and days 6 and 7 for delayed CINV prophylaxis in a double-blind, randomized, crossover study design.

Description:

OUTLINE: This is a multi-center trial.

Subjects will be stratified prior to randomization based on previous administration of chemotherapy.

Subjects will randomize to aprepitant versus placebo with their first study cycle of chemotherapy and then cross over to opposite arm with the second study cycle.

Arm A, Study Cycle 1:

Aprepitant 125mg PO day 3 then 80mg on days 4 through 7

Arm A, Study Cycle 2:

Matched placebo PO daily on days 3 through 7

Arm B, Study Cycle 1:

Matched placebo PO daily on days 3 through 7

Arm B, Study Cycle 2:

Aprepitant 125mg PO day 3 then 80mg on days 4 through 7

Cisplatin-based regimen for germ cell tumors containing 20mg/m2/day IV days 1 through 5, first day of chemotherapy administration is day 1. Permitted treatment regimens:

Regimen 1 (BEP) Cisplatin (20mg/m2/day) IV on days 1 to 5 Etoposide (100 mg/m2/day) IV on days 1 to 5 Bleomycin 30 U/IV on days 1, 8, 15

Regimen 2 (EP) Cisplatin (20mg/m2/day) IV on days 1 to 5 Etoposide (100 mg/m2/day) IV on days 1 to 5

Regimen 3 (VIP) Cisplatin (20mg/m2/day) IV on days 1 to 5 Ifosfamide (1200 mg/m2/day) IV on days 1 to 5 (with mesna uroprophylaxis at 100% ifosfamide dosing) Etoposide (75 mg/m2/day) IV on days 1 to 5

Regimen 4 (VeIP) Cisplatin (20mg/m2/day) IV on days 1 to 5 Ifosfamide (1200 mg/m2/day) IV on days 1 to 5 (with mesna uroprophylaxis at 100% ifosfamide dosing) Vinblastine (0.11 mg/kg/day) IV on days 1 and 2

Regimen 5 (EC) Cisplatin (20mg/m2/day) IV on days 1 to 5 Epirubicin (90 mg/m2/day) IV on day 1

Patients are treated on study for two cycles. At the completion of protocol therapy patients will receive additional chemotherapy at the discretion of the treating investigator.

If a patient requires discontinuation of one medication or more on a regimen, the patient must be discontinued from the study.

Performance Status:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• Bilirubin < 3 x upper limit of normal

• Aspartate aminotransferase (AST, SGOT) < 3 x upper limit of normal

• Alanine aminotransferase (ALT, SGPT) < 3 x upper limit of normal

• Alk Phos < 3 x upper limit of normal

Renal:

• Serum Creatinine <2 mg/dL

Pulmonary:

• Not specified

Recruitment information / eligibility

• Status: Completed
• Enrollment: 71
• Est. completion date: February 2011
• Est. primary completion date: December 2010
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 15 Years and older

Eligibility

Inclusion Criteria:

• Histologic, serologic or clinical evidence of germ cell tumor.

• Patients scheduled to receive a 5 day fractionated cisplatin-based combination chemotherapy on permitted regimens

• Prior chemotherapy is allowed. Patients will be stratified based on previous treatment.

• Male patients 15 years of age or older at time of registration.

• Patient will provide written informed consent and authorization to release personal health information.

Exclusion Criteria:

• No known history of anticipatory nausea or vomiting.

• No use of another antiemetic agent within 72 hours prior to beginning chemotherapy.

• No known CNS metastasis.

• No known hypersensitivity to any component of study regimen.

• No concurrent participation in a clinical trial which involves another investigational agent.

• No use of warfarin while on study.

• No use of agents expected to induce the metabolism of aprepitant which include:

Rifampin, Rifabutin, Phenytoin, Carbamazepine, and barbiturates.

• No use of agents which may impair metabolism of aprepitant which include: Cisapride, macrolide antibiotics (Erythromycin, Clarithromycin, Azithromycin), azole antifungal agents (Ketoconazole, Itraconazole, Voriconazole, Fluconazole), Amifostine, Nelfinavir and Ritonavir.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Germ Cell Tumors
• Neoplasms, Germ Cell and Embryonal

Intervention

Drug:
• Aprepitant
Aprepitant 125mg PO day 3 then 80mg on days 4 through 7 Subjects will be stratified prior to randomization based on previous administration of chemotherapy. Subjects will randomize to aprepitant versus placebo with their first study cycle of chemotherapy and then cross over to opposite arm with the second study cycle. Arm A, Study Cycle 1 Arm B, Study Cycle 2
• Placebo
Matched placebo PO daily on days 3 through 7 Subjects will be stratified prior to randomization based on previous administration of chemotherapy. Subjects will randomize to aprepitant versus placebo with their first study cycle of chemotherapy and then cross over to opposite arm with the second study cycle. Arm A, Study Cycle 2 Arm B, Study Cycle 1

Locations

Country	Name	City	State
United States	Indiana University Simon Cancer Center	Indianapolis	Indiana
United States	Froedtert/Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Medical Consultants, P.C.	Muncie	Indiana
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Providence Portland Medical Center	Portland	Oregon
United States	Siteman Cancer Center	St. Louis	Missouri

Sponsors (2)

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

Country where clinical trial is conducted

United States, 

References & Publications (1)

Albany C, Brames MJ, Fausel C, Johnson CS, Picus J, Einhorn LH. Randomized, double-blind, placebo-controlled, phase III cross-over study evaluating the oral neurokinin-1 antagonist aprepitant in combination with a 5HT3 receptor antagonist and dexamethason — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To compare aprepitant with placebo in addition to standard antiemetic prophylaxis in preventing acute (days 1 through 5) and delayed (days 6 through 8) CINV measured by the proportion of patients with a Complete Response.		2 months	No
Secondary	To compare aprepitant with placebo in addition to standard antiemetic prophylaxis in preventing acute and delayed CINV measured by the proportion of patients with no emesis.		2 months	No
Secondary	To compare aprepitant with placebo in addition to standard antiemetic prophylaxis in preventing acute (days 1 through 5) and delayed (days 6 through 8) CINV measured by the proportion of patients with no nausea.		2 months	No
Secondary	To compare aprepitant with placebo in addition to standard antiemetic prophylaxis in preventing acute (days 1 through 5) and delayed (days 6 through 8) CINV measured by presence of symptoms measured by the MD Anderson Symptom Inventory.		2 months	No
Secondary	To compare aprepitant with placebo in addition to standard antiemetic prophylaxis in preventing acute and delayed CINV measured by the proportion of patients who state a preference for either aprepitant or placebo.		2 months	No
Secondary	To explore prevalence of polymorphisms of genes that encode for drug metabolizing enzymes, receptors, and drug transporters involved in the activity of anti-emetics used in the prophylaxis of CINV in patients with GCT.		2 months	No

External Links

•   Hoosier Oncology Group Home Page