Malignant Neoplasm
Conditions
Brief summary
This phase II trial studies how well netupitant and palonosetron hydrochloride work in preventing chemotherapy induced nausea and vomiting in patients with cancer undergoing BEAM conditioning regimen before stem cell transplant. Chemotherapy, such as carmustine, cytarabine, etoposide, and melphalan (BEAM), makes people feel sick to their stomach and causes vomiting. Netupitant and palonosetron hydrochloride may reduce the nausea and vomiting caused by the BEAM treatment.
Detailed description
PRIMARY OBJECTIVES: I. To assess the efficacy of netupitant and palonosetron hydrochloride (NEPA) to prevent nausea and vomiting both during and after a highly emetogenic (BEAM) conditioning regimen for hematopoietic stem cell transplantation (HSCT). SECONDARY OBJECTIVES: I. To differentiate response to NEPA over different phases of chemotherapy-induced nausea. OUTLINE: Within 60 minutes before standard of care BEAM treatment, patients receive netupitant and palonosetron hydrochloride orally (PO) on days 1, 3, and 6. After completion of study treatment, patients are followed up at 14 days.
Interventions
0.5 mg, Given PO, QD
OTHERQuestionnaire Administration
Ancillary studies
DRUGNetupitant
300 mg, Given PO, QD
Sponsors
Helsinn Therapeutics (U.S.), Inc
Oregon Health and Science University
OHSU Knight Cancer Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects must be undergoing autologous or allogeneic hematopoietic stem cell transplant (HSCT) with the BEAM conditioning regimen prior to HSCT * Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 or Karnofsky Performance Score \>= 60% * Able to swallow oral medications * Ability to understand and the willingness to sign a written informed consent document
Exclusion criteria
* Subjects with known hypersensitivity or other allergic reactions attributed to compounds of similar biologic composition to netupitant, palonosetron, dexamethasone, or other agents used in the study * Subjects who are receiving any other investigational agents or have received another investigational drug in the last 30 days * Subjects who have had emesis or required antiemetics in the 48 hours prior to starting the BEAM conditioning regimen; patients required to take antipsychotics, appetite stimulants, or other medications with antiemetic effects will also be excluded if those medications cannot be replaced by therapeutic equivalents * Female subjects who are pregnant, have a positive serum human chorionic gonadotrophin (hCG), or are lactating and intend to breastfeed a child; pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with NEPA * Human immunodeficiency virus (HIV)-positive subjects on combination antiretroviral therapy are ineligible * Subjects who have taken a neurokinin antagonist within 14 days prior to beginning the BEAM regimen * Subjects who have a serum creatinine \> 2 x upper limit of normal (ULN) * Subjects with severe renal failure or end stage renal disease (estimated GFR \[glomerular filtration rate\] of \< 30 mL/min) as estimated by the Cockcroft-Gault formula * Subjects with severe hepatic insufficiency (Child Pugh score \> 9) * Subjects who have been reported \> 5 alcoholic drinks daily for the last year * Subjects who have concurrent illness requiring systemic corticosteroid use other than the planned dexamethasone during conditioning therapy * Subjects with gastrointestinal conditions that might result in malabsorption of the study drug * Subjects with a history of anxiety-induced (anticipatory) nausea and vomiting * Subjects on strong CYP 3A4 inducers or inhibitors who are unable to have those agents replaced with clinical alternatives prior to beginning the study; length of washout period will be 7 days; notably, in the case of allogeneic transplant recipients requiring cyclosporine or tacrolimus, no empiric dose adjustments will be required due to close level monitoring and adjustments, that are standard in Oregon Health & Science University (OHSU) protocols * Subjects unable to discontinue benzodiazepines as antiemetics will not be allowed; additional antiemetics will be allowed for rescue but not for prophylaxis * Subjects with personal or family history of QT prolongation, uncorrected electrolyte abnormalities, congestive heart failure, bradyarrhythmia, conduction disturbances and those taking antiarrhythmic medicinal products or other medicinal products that lead to QT prolongation or electrolyte abnormalities; relevant information will be collected as part of subject medical history
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete Response (CR) Defined as no Emesis and no Rescue Therapy | Up to 5 days post chemotherapy | Number of subjects that reached a complete response (CR), defined as having no emesis and no rescue therapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| CR (Acute Phase) | Up to 144 hours post-study drug administration on day 1 | Number of subjects that reached a complete response (CR), defined as having no emesis and no rescue therapy from 0 to 144 hours (acute phase) of the study drug administration. |
| CR (Delayed Phase) | From 145 hours up to 264 hours post-study drug administration on day 1 | Number of subjects that reached a complete response (CR), defined as having no emesis and no rescue therapy from 145 hours up to 264 hours (delayed phase) of the study drug administration. |
| Complete Protection (CP) Rate Defined as CR Plus no Nausea | Up to 264 hours post-study drug administration on day 1 | Number of subjects that reached a complete response (CR), defined as having no emesis and no rescue therapy from 0 to 264 hours of the study drug administration. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Time to First Emesis and Time to Receiving First Rescue Medication | Up to 264 hours | Will be depicted via Kaplan-Meier curves showing the percentage of patients who had no emesis or rescue medication use for the acute and delayed time periods. |
| Number of Participants With Emetic Episodes and Received Rescue Agents | Up to 264 hours | The number of participants that had emetic episodes and received rescue agents (medications). |
| Time to Receiving First Rescue Medication and First Emesis | Up to 264 hours | Will be depicted via Kaplan-Meier curves showing the percentage of patients who had no emesis or rescue medication use for the acute and delayed time periods. |
| Number of Participants With Emetic Episodes and Received Rescue Agents (Acute Phase) | Up to 144 hours post-study drug administration on day 1 | The number of participants that had emetic episodes and received rescue agents (medications) (acute phase: for 0 to 144 hours timeframe of study drug administration) |
| Number of Participants With Emetic Episodes and Received Rescue Agents (Delayed Phase) | From 145 hours up to 264 hours post-study drug administration on day 1 | The number of participants that had emetic episodes and received rescue agents (medications) during the delayed phase (for 145 hours up to 264 hours timeframe) |
| Mean Levels of Nausea Per Day Assessed by Chemotherapy Induced Nausea and Vomiting Questionnaire | Up to 11 days | The mean level of nausea per day assessed by chemotherapy induced nausea and vomiting questionnaire. The full range of nausea level score on the questionnaire was from minimum value of 0 to a maximum value of 10. 0= no nausea or vomiting, and 10= worst nausea and vomiting. Higher score means a worse outcome. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Supportive Care (NEPA) Within 60 minutes before standard of care BEAM treatment, patients receive netupitant and palonosetron hydrochloride PO on days 1, 3, and 6.
Netupitant: 300 mg, QD, Given PO Palonosetron Hydrochloride: 0.5 mg, QD, Given PO Questionnaire Administration: Ancillary studies | 43 |
| Total | 43 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
Baseline characteristics
| Characteristic | Supportive Care (NEPA) |
|---|---|
| Age, Continuous | 55 years |
| Race/Ethnicity, Customized Race Black or African American | 1 Participants |
| Race/Ethnicity, Customized Race Native Hawaiian/other Pacific Highlander | 1 Participants |
| Race/Ethnicity, Customized Race White | 41 Participants |
| Sex: Female, Male Female | 16 Participants |
| Sex: Female, Male Male | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 43 |
| other Total, other adverse events | 43 / 43 |
| serious Total, serious adverse events | 1 / 43 |
Outcome results
Primary
Complete Response (CR) Defined as no Emesis and no Rescue Therapy
Number of subjects that reached a complete response (CR), defined as having no emesis and no rescue therapy.
Time frame: Up to 5 days post chemotherapy
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Supportive Care (NEPA) | Complete Response (CR) Defined as no Emesis and no Rescue Therapy | 13 Participants |
Secondary
Complete Protection (CP) Rate Defined as CR Plus no Nausea
Number of subjects that reached a complete response (CR), defined as having no emesis and no rescue therapy from 0 to 264 hours of the study drug administration.
Time frame: Up to 264 hours post-study drug administration on day 1
Population: 42 participants completed the study and therefore were analyzed for response.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Supportive Care (NEPA) | Complete Protection (CP) Rate Defined as CR Plus no Nausea | 3 Participants |
Secondary
CR (Acute Phase)
Number of subjects that reached a complete response (CR), defined as having no emesis and no rescue therapy from 0 to 144 hours (acute phase) of the study drug administration.
Time frame: Up to 144 hours post-study drug administration on day 1
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Supportive Care (NEPA) | CR (Acute Phase) | 12 Participants |
Secondary
CR (Delayed Phase)
Number of subjects that reached a complete response (CR), defined as having no emesis and no rescue therapy from 145 hours up to 264 hours (delayed phase) of the study drug administration.
Time frame: From 145 hours up to 264 hours post-study drug administration on day 1
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Supportive Care (NEPA) | CR (Delayed Phase) | 1 Participants |
Other Pre-specified
Mean Levels of Nausea Per Day Assessed by Chemotherapy Induced Nausea and Vomiting Questionnaire
The mean level of nausea per day assessed by chemotherapy induced nausea and vomiting questionnaire. The full range of nausea level score on the questionnaire was from minimum value of 0 to a maximum value of 10. 0= no nausea or vomiting, and 10= worst nausea and vomiting. Higher score means a worse outcome.
Time frame: Up to 11 days
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Supportive Care (NEPA) | Mean Levels of Nausea Per Day Assessed by Chemotherapy Induced Nausea and Vomiting Questionnaire | 2.79 score on a scale |
Other Pre-specified
Number of Participants With Emetic Episodes and Received Rescue Agents
The number of participants that had emetic episodes and received rescue agents (medications).
Time frame: Up to 264 hours
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Supportive Care (NEPA) | Number of Participants With Emetic Episodes and Received Rescue Agents | Number of participants who had emetic episodes | 8 Participants |
| Supportive Care (NEPA) | Number of Participants With Emetic Episodes and Received Rescue Agents | Number of participants who were given rescue meds | 36 Participants |
Other Pre-specified
Number of Participants With Emetic Episodes and Received Rescue Agents (Acute Phase)
The number of participants that had emetic episodes and received rescue agents (medications) (acute phase: for 0 to 144 hours timeframe of study drug administration)
Time frame: Up to 144 hours post-study drug administration on day 1
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Supportive Care (NEPA) | Number of Participants With Emetic Episodes and Received Rescue Agents (Acute Phase) | Number of participants who had an emetic episode in acute phase | 0 Participants |
| Supportive Care (NEPA) | Number of Participants With Emetic Episodes and Received Rescue Agents (Acute Phase) | Number of participants who were given rescue meds in acute phase | 13 Participants |
Other Pre-specified
Number of Participants With Emetic Episodes and Received Rescue Agents (Acute Phase)
The number of participants that had emetic episodes and received rescue agents (medications) (for 0 to 24 hours timeframe of study drug administration)
Time frame: Up to 24 hours post-study drug administration on day 1
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Supportive Care (NEPA) | Number of Participants With Emetic Episodes and Received Rescue Agents (Acute Phase) | Number of participants that had emetic episodes | 0 Participants |
| Supportive Care (NEPA) | Number of Participants With Emetic Episodes and Received Rescue Agents (Acute Phase) | Number of participants that were given rescue meds- | 2 Participants |
Other Pre-specified
Number of Participants With Emetic Episodes and Received Rescue Agents (Delayed Phase)
The number of participants that had emetic episodes and received rescue agents (medications) during the delayed phase (for 145 hours up to 264 hours timeframe)
Time frame: From 145 hours up to 264 hours post-study drug administration on day 1
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Supportive Care (NEPA) | Number of Participants With Emetic Episodes and Received Rescue Agents (Delayed Phase) | The number of participants that had an emetic episode | 8 Participants |
| Supportive Care (NEPA) | Number of Participants With Emetic Episodes and Received Rescue Agents (Delayed Phase) | The number of participants that were given rescue meds | 23 Participants |
Other Pre-specified
Time to First Emesis and Time to Receiving First Rescue Medication
Will be depicted via Kaplan-Meier curves showing the percentage of patients who had no emesis or rescue medication use for the acute and delayed time periods.
Time frame: Up to 264 hours
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Supportive Care (NEPA) | Time to First Emesis and Time to Receiving First Rescue Medication | Time to first emesis | 216 Hours |
| Supportive Care (NEPA) | Time to First Emesis and Time to Receiving First Rescue Medication | Median time to receiving rescue medication | 148.4 Hours |
Other Pre-specified
Time to Receiving First Rescue Medication and First Emesis
Will be depicted via Kaplan-Meier curves showing the percentage of patients who had no emesis or rescue medication use for the acute and delayed time periods.
Time frame: Up to 264 hours
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Supportive Care (NEPA) | Time to Receiving First Rescue Medication and First Emesis | Mean time to first rescue medication | 143 Hours | Standard Deviation 55.27 |
| Supportive Care (NEPA) | Time to Receiving First Rescue Medication and First Emesis | Mean time to first emesis | 8.9 Hours | Standard Deviation 0.83 |