Germ Cell Tumors
Conditions
Brief 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.
Detailed 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 or placebo with their first study cycle of chemotherapy and then cross over to opposite treatment with the second study cycle. 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
Interventions
DRUGAprepitant
Subjects will be randomized to receive aprepitant 125mg PO day 3 then 80mg on days 4-7 on either cycle 1 or cycle 2.
DRUGPlacebo
Subjects will be randomized to receive placebo on days 3-7 on either cycle 1 or cycle 2.
Sponsors
Merck Sharp & Dohme LLC
Hoosier Cancer Research Network
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
SUPPORTIVE_CARE
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
MALE
Age
15 Years to No maximum
Healthy volunteers
No
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 central nervous system (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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete Response. | Participants were evaluated from start of treatment through day 8 of cycle 2. | Participants were followed for chemotherapy induced nausea and vomiting (CINV) through day 8 of cycle 2. Complete response is defined as no emetic episodes and no use of rescue medication. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Patients With no Emesis During the Acute CINV Time Period (Cycle Days 1-5) | Participants were evaluated from cycle days 1-5. | Proportion of patients with no emesis regardless of use of rescue medication during cycle days 1-5. |
| Proportion of Patients With no Emesis During the Delayed CINV Time Period (Cycle Days 6-8) | Participants were evaluated from cycle days 6-8. | Proportion of patients with no emesis regardless of use of rescue medication during cycle days 6-8. |
| Visual Analouge (VAS) 100mm Scale Score | Days 1-8 | 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. The mean VAS scores for days 1-8 combined, by treatment (Aprepitant vs. Placebo) were reported. |
| MD Anderson Symptom Inventory Score | Days 1-8 | The MD Anderson Symptom Inventory (MDASI) is a brief measure of the severity and impact of cancer-related symptoms. Thirteen core items measure the severity of symptoms and six additional items measure the impact of symptoms. All items are rated on a scale from 0 (not present or did not interfere) to 10 (maximal severity or interference). The mean value of the total nineteen items ranges from 0 to 10. |
| Preferred Treatment Cycle | 2 months | Participants were asked which treatment cycles was preferable - aprepitant or placebo cycle. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm A: Aprepitant, Then Placebo Participants first received Aprepitant 125mg PO day 3 then 80mg on days 4 and 7 during study cycle 1, then received matched placebo PO daily on days 3 through 7 during study cycle 2
Aprepitant: Subjects will be randomized to receive aprepitant 125mg PO day 3 then 80mg on days 4-7 on either cycle 1 or cycle 2.
Placebo: Subjects will be randomized to receive placebo on days 3-7 on either cycle 1 or cycle 2. | 35 |
| Arm B: Placebo, Then Aprepitant Participants first received matched placebo PO daily on days 3 through 7 during study cycle 1, then received Aprepitant 125mg PO day 3 then 80mg on days 4 and 7 during study cycle 2
Aprepitant: Subjects will be randomized to receive aprepitant 125mg PO day 3 then 80mg on days 4-7 on either cycle 1 or cycle 2.
Placebo: Subjects will be randomized to receive placebo on days 3-7 on either cycle 1 or cycle 2. | 34 |
| Total | 69 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 3 | 6 |
Baseline characteristics
| Characteristic | Arm A: Aprepitant, Then Placebo | Arm B: Placebo, Then Aprepitant | Total |
|---|---|---|---|
| Age, Continuous | 34 years STANDARD_DEVIATION 11.2 | 30 years STANDARD_DEVIATION 8.6 | 31 years STANDARD_DEVIATION 10.16 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 34 Participants | 33 Participants | 67 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Prior Therapies Chemotherapy Multiple Agent Systemic (CMAS) | 5 participants | 5 participants | 10 participants |
| Prior Therapies CMAS and Surgery | 1 participants | 1 participants | 2 participants |
| Prior Therapies No Prior Therapy | 29 participants | 28 participants | 57 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 35 Participants | 32 Participants | 67 Participants |
| Region of Enrollment United States | 35 participants | 34 participants | 69 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 35 Participants | 34 Participants | 69 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 34 / 35 | 32 / 34 |
| serious Total, serious adverse events | 7 / 35 | 9 / 34 |
Outcome results
Primary
Complete Response.
Participants were followed for chemotherapy induced nausea and vomiting (CINV) through day 8 of cycle 2. Complete response is defined as no emetic episodes and no use of rescue medication.
Time frame: Participants were evaluated from start of treatment through day 8 of cycle 2.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aprepitant | Complete Response. | 47 percentage of evaluable subjects |
| Placebo | Complete Response. | 15 percentage of evaluable subjects |
Secondary
MD Anderson Symptom Inventory Score
The MD Anderson Symptom Inventory (MDASI) is a brief measure of the severity and impact of cancer-related symptoms. Thirteen core items measure the severity of symptoms and six additional items measure the impact of symptoms. All items are rated on a scale from 0 (not present or did not interfere) to 10 (maximal severity or interference). The mean value of the total nineteen items ranges from 0 to 10.
Time frame: Days 1-8
Population: There were 64 subjects during the Aprepitant treatment and 62 subjects during the Placebo treatment for days 1-8 that had complete data for the analysis of the M.D. Anderson Symptom Inventory. The mean MDASI scores for days 1-8 combined, by treatment (Aprepitant vs. Placebo) were reported.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aprepitant | MD Anderson Symptom Inventory Score | 3.2 units on a scale | Standard Deviation 3.4 |
| Placebo | MD Anderson Symptom Inventory Score | 2.9 units on a scale | Standard Deviation 2.6 |
Secondary
Preferred Treatment Cycle
Participants were asked which treatment cycles was preferable - aprepitant or placebo cycle.
Time frame: 2 months
Population: There were 49 subjects during the Aprepitant treatment and the Placebo treatment for each cycle that had complete data for the analysis of the preferred treatment cycle.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aprepitant | Preferred Treatment Cycle | 78 percentage of subjects with a preference |
| Placebo | Preferred Treatment Cycle | 22 percentage of subjects with a preference |
Secondary
Proportion of Patients With no Emesis During the Acute CINV Time Period (Cycle Days 1-5)
Proportion of patients with no emesis regardless of use of rescue medication during cycle days 1-5.
Time frame: Participants were evaluated from cycle days 1-5.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aprepitant | Proportion of Patients With no Emesis During the Acute CINV Time Period (Cycle Days 1-5) | 80 percentage of evaluable subjects |
| Placebo | Proportion of Patients With no Emesis During the Acute CINV Time Period (Cycle Days 1-5) | 52 percentage of evaluable subjects |
Secondary
Proportion of Patients With no Emesis During the Delayed CINV Time Period (Cycle Days 6-8)
Proportion of patients with no emesis regardless of use of rescue medication during cycle days 6-8.
Time frame: Participants were evaluated from cycle days 6-8.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aprepitant | Proportion of Patients With no Emesis During the Delayed CINV Time Period (Cycle Days 6-8) | 92 percentage of evaluable subjects |
| Placebo | Proportion of Patients With no Emesis During the Delayed CINV Time Period (Cycle Days 6-8) | 78 percentage of evaluable subjects |
Secondary
Visual Analouge (VAS) 100mm Scale Score
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. The mean VAS scores for days 1-8 combined, by treatment (Aprepitant vs. Placebo) were reported.
Time frame: Days 1-8
Population: There were 54 subjects during the Aprepitant treatment and 61 subjects during the Placebo treatment for days 1-8 that had complete data for the analysis of the visual analouge scale for nausea and vomiting.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aprepitant | Visual Analouge (VAS) 100mm Scale Score | 22.6 mm | Standard Deviation 18.7 |
| Placebo | Visual Analouge (VAS) 100mm Scale Score | 27.1 mm | Standard Deviation 22.1 |