Chemotherapy-Induced Nausea and Vomiting
Conditions
Keywords
Fosaprepitant, 5HT3 Receptor Antagonists, Dexamethasone, Germ Cell Tumors, Testis Cancer, Rescue Medications
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
Interventions
DRUGFosaprepitant
Fosaprepitant 150mg IV D3 for acute prophylaxis Fosaprepitant 150mg IV on Day 5 for delayed prophylaxis
DRUGDexamethasone
Dexamethasone 20mg PO daily on D1 and 2 for acute prophylaxis Dexamethasone 4mg PO BID on Days 6 through 8
DRUG5HT3
Any 5HT3RA on D1-5; D1, 3 and 5 if palonosetron is used.
Sponsors
Hoosier Cancer Research Network
Merck Sharp & Dohme LLC
Lawrence Einhorn
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
15 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Complete Response of Acute and Delayed Chemotherapy Induced Nausea and Vomiting | Days 1-8 of chemotherapy regimen | complete response (CR) of both acute (days 1 through 5) and delayed (days 6 through 8) CINV, defined by no emetic episodes or use of rescue medications |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total Number of Emetic Episodes | Days 1-8 of chemotherapy regimen | total number of emetic episodes |
| Use of Rescue Medications. | Days 1-8 of chemotherapy regimen | Total number of patients who received rescue medications. |
| Self-Reported Assessment of Nausea | Days 1-8 of chemotherapy regimen | the patient's self-reported assessment of nausea Days 1-8 using a 0-100mm visual analog scale (VAS) median. 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. Median VAS scores (in mm) are reported, per day. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Fosaprepitant + 5HT3 Receptor Antagonists + Dexamethasone 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).
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
Fosaprepitant: Fosaprepitant 150mg IV D3 for acute prophylaxis Fosaprepitant 150mg IV on Day 5 for delayed prophyl | 64 |
| Total | 64 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Protocol Violation | 10 |
Baseline characteristics
| Characteristic | Fosaprepitant + 5HT3 Receptor Antagonists + Dexamethasone |
|---|---|
| Age, Continuous | 33 years |
| Cancer Stage Cancer Stage I | 27 participants |
| Cancer Stage Cancer Stage II | 24 participants |
| Cancer Stage Cancer Stage III | 11 participants |
| Cancer Stage Cancer Stage IS | 1 participants |
| Cancer Stage Cancer Stage Unknown | 1 participants |
| Chemotherapy Regimen Bleomycin, etoposide, cisplatin | 51 participants |
| Chemotherapy Regimen Cisplatin, Epirubicin | 1 participants |
| Chemotherapy Regimen Etoposide, cisplatin | 10 participants |
| Chemotherapy Regimen Vinblastine, ifosfamide, cisplatin | 2 participants |
| Eastern Cooperative Oncology Group (ECOG) performance status ECOG PS 0 | 59 participants |
| Eastern Cooperative Oncology Group (ECOG) performance status ECOG PS 1 | 4 participants |
| Eastern Cooperative Oncology Group (ECOG) performance status ECOG PS 2 | 1 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 61 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Prior Chemotherapy Participants without Prior Chemotherapy | 59 participants |
| Prior Chemotherapy Participants with Prior Chemotherapy | 5 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 64 Participants |
| Region of Enrollment United States | 64 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 64 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 65 / 65 |
| serious Total, serious adverse events | 9 / 65 |
Outcome results
Primary
Percentage of Participants With Complete Response of Acute and Delayed Chemotherapy Induced Nausea and Vomiting
complete response (CR) of both acute (days 1 through 5) and delayed (days 6 through 8) CINV, defined by no emetic episodes or use of rescue medications
Time frame: Days 1-8 of chemotherapy regimen
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Fosaprepitant + 5HT3 Receptor Antagonists + Dexamethasone | Percentage of Participants With Complete Response of Acute and Delayed Chemotherapy Induced Nausea and Vomiting | acute phase(days 1 through 5) | 29.6 percentage of participants |
| Fosaprepitant + 5HT3 Receptor Antagonists + Dexamethasone | Percentage of Participants With Complete Response of Acute and Delayed Chemotherapy Induced Nausea and Vomiting | delayed phase (days 6 through 8) | 46.3 percentage of participants |
| Fosaprepitant + 5HT3 Receptor Antagonists + Dexamethasone | Percentage of Participants With Complete Response of Acute and Delayed Chemotherapy Induced Nausea and Vomiting | overall | 24.1 percentage of participants |
Secondary
Self-Reported Assessment of Nausea
the patient's self-reported assessment of nausea Days 1-8 using a 0-100mm visual analog scale (VAS) median. 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. Median VAS scores (in mm) are reported, per day.
Time frame: Days 1-8 of chemotherapy regimen
Population: 54 patients completed the VAS on all 8 days and were eligible for analysis.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Fosaprepitant + 5HT3 Receptor Antagonists + Dexamethasone | Self-Reported Assessment of Nausea | median VAS score - day 8 | 3 millimeters |
| Fosaprepitant + 5HT3 Receptor Antagonists + Dexamethasone | Self-Reported Assessment of Nausea | median VAS score - day 1 | 0 millimeters |
| Fosaprepitant + 5HT3 Receptor Antagonists + Dexamethasone | Self-Reported Assessment of Nausea | median VAS score - day 2 | 0 millimeters |
| Fosaprepitant + 5HT3 Receptor Antagonists + Dexamethasone | Self-Reported Assessment of Nausea | median VAS score - day 3 | 4.5 millimeters |
| Fosaprepitant + 5HT3 Receptor Antagonists + Dexamethasone | Self-Reported Assessment of Nausea | median VAS score - day 4 | 18.5 millimeters |
| Fosaprepitant + 5HT3 Receptor Antagonists + Dexamethasone | Self-Reported Assessment of Nausea | median VAS score - day 5 | 23.5 millimeters |
| Fosaprepitant + 5HT3 Receptor Antagonists + Dexamethasone | Self-Reported Assessment of Nausea | median VAS score - day 6 | 12.5 millimeters |
| Fosaprepitant + 5HT3 Receptor Antagonists + Dexamethasone | Self-Reported Assessment of Nausea | median VAS score - day 7 | 7 millimeters |
Secondary
Total Number of Emetic Episodes
total number of emetic episodes
Time frame: Days 1-8 of chemotherapy regimen
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fosaprepitant + 5HT3 Receptor Antagonists + Dexamethasone | Total Number of Emetic Episodes | 29 episodes |
Secondary
Use of Rescue Medications.
Total number of patients who received rescue medications.
Time frame: Days 1-8 of chemotherapy regimen
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fosaprepitant + 5HT3 Receptor Antagonists + Dexamethasone | Use of Rescue Medications. | 37 participants |