Breakthrough Nausea and Vomiting, Unspecified Adult Solid Tumor, Protocol Specific
Conditions
Keywords
nausea and vomiting, unspecified adult solid tumor, protocol specific
Brief summary
RATIONALE: Antiemetic drugs, such as fosaprepitant dimeglumine, may help lessen or prevent nausea and vomiting in patients treated with chemotherapy. PURPOSE: This clinical trial is studying the side effects of fosaprepitant dimeglumine and to see how well it works in treating patients with nausea and vomiting caused by chemotherapy.
Detailed description
OBJECTIVES: Primary * To evaluate the efficacy and safety of fosaprepitant dimeglumine in patients with breakthrough chemotherapy-induced nausea and vomiting (CINV) after failing prophylactic antiemetic therapy. Secondary * To evaluate toxicity and serious adverse events associated with this regimen in these patients. * To evaluate the ability of patients to tolerate oral intake. * To evaluate the health-related quality of life of patients treated with this regimen. * To evaluate specific side effects associated with this regimen, including pain sensation and/or soreness at the infusion site, headache, dizziness, and somnolence, in these patients . * To refine the study design for future phase II and III studies of rescue therapy for breakthrough CINV using various secondary endpoints. OUTLINE: Patients receive chemotherapy in combination with a pre-defined standard 5-Hydroxytryptamine-3 (5-HT3) antagonist or corticosteroid regimen with or without a benzodiazepine on day 1. If breakthrough nausea or vomiting occurs, patients then receive fosaprepitant dimeglumine IV once per standard administration guidelines. Patients with treatment response may receive additional doses of oral aprepitant once on days 2 and 3. Patients with persistent nausea/vomiting after 2 hours and who desire further treatment may receive standard rescue therapy with prochlorperazine, metoclopramide, or haloperidol with or without additional lorazepam until relief, at the discretion of the provider. Patients complete a diary at baseline, and then at 2, 12, and 24 hours that includes a Visual Analogue Scale (VAS) for nausea; VAS for sedation; and questions about emesis and retching frequency, headache, dizziness, somnolence, and ability to take food and liquids orally. Patients also complete the Functional Living Index-Emesis Quality of Life survey at baseline and at 24 hours.
Interventions
A 150 mg dose will be given to study patients as rescue therapy after chemotherapy only in the event of breakthrough nausea or vomiting.
DRUGsystemic chemotherapy
Patients will receive chemotherapy on Day 1 of their scheduled therapeutic regimen in combination with the pre-defined standard 5-Hydroxytryptamine-3 (5HT3) antagonist, corticosteroid regimen, with or without benzodiazepine based on published guidelines3 or as clinically indicated
OTHERsurvey administration
Prior to the first dose of chemotherapy patients will be instructed on how to complete their patient diary
PROCEDUREquality-of-life assessment
Patients will also be provided the Functional Living Index - Emesis (FLIE) quality of life survey to be completed at time zero and then after 24 hours
Sponsors
National Cancer Institute (NCI)
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 120 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Diagnosis of cancer * Scheduled to receive inpatient chemotherapy containing at least moderately emetogenic agents * May be given for adjuvant, neoadjuvant, curative, or palliative intent * May be given orally, IV, or by continuous infusion on ≥ 1 day * Scheduled to receive 5-HT3 receptor antagonist antiemetic (e.g., ondansetron, granisetron, palonosetron, dolasetron mesylate, or dexamethasone with or without a benzodiazepine) on the day of chemotherapy * Self-report of at least mild nausea (for which the patient feels needs rescuing) or moderate nausea (a score of ≥ 2 on a 4-point Likert scale) OR has had ≥ 1 episode of emesis since receiving chemotherapy * No history of chronic nausea and/or vomiting (without chemotherapy), anticipatory nausea and/or vomiting, or emesis within 24 hours before chemotherapy * No symptomatic brain metastases PATIENT CHARACTERISTICS: * Able to understand English * Not pregnant or nursing * Negative pregnancy test * No clinical evidence of current or impending bowel obstruction (i.e., tumor pressing on the bowel) * No allergy or intolerance to study drugs PRIOR CONCURRENT THERAPY: * See Disease Characteristics * Prior chemotherapy allowed * No aprepitant as prophylaxis or rescue treatment during the current course of chemotherapy (other than as a part of study therapy) * Not scheduled to receive a dopamine antagonist after chemotherapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Improvement in Nausea Score From Baseline to 2 Hours as Assessed by the Numerical Visual Analogue Scale | Baseline to 2 hours after study drug administered. | The outcome measure is the number of participants that self report improvement in a nausea score from baseline, prior to fosaprepitant, to 2 hours post dose. This includes only participants who report breakthrough nausea or vomiting after chemotherapy and after receiving prophylactic anti-emetics. The primary outcome is measured using the visual analogue scale, a self report scale from No Nausea to Nausea as bad as it can be; a value can be indicated anywhere on this scale using a free hand mark by the participant and gauged with ruler by study staff. Any participant that reported a lower value on the scale 2 hours from baseline would be considered in this outcome measure. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Improvement in Nausea Score From 2 Hours to 24 Hours | 2 hours to 24 hours after study drug administered. | The outcome measure is the number of participants that self report improvement in a nausea score from 2 hours after receiving fosaprepitant to 24 hours post dose. This includes only participants who report breakthrough nausea or vomiting after chemotherapy and after receiving prophylactic anti-emetics. The outcome is measured using the visual analogue scale, a self report scale from No Nausea to Nausea as bad as it can be; a value can be indicated anywhere on this scale using a free hand mark by the participant and gauged with ruler by study staff. Any participant reporting a lower value on the scale at the 12 or 24 hour time point would be considered in this outcome measure. |
| Number of Participants Who Experienced Vomiting Episodes From Baseline to 24 Hours | Baseline to 24 hours after study drug administered. | Participants were asked to report any episodes of vomiting before (baseline) and up to 24 hours after receiving Fosaprepitant. The outcome considers the number of participants reporting any episodes of emesis after receiving Fosaprepitant. |
| Participants Who Required the Use of Second Rescue Drug (Time to Treatment Failure) | 2 hours after administration of Fosaprepitant 150 mg IV | Participants with persistent nausea/vomiting after 2 hours and who desired further treatment, received standard rescue therapy at the discretion of provider with prochlorperazine, metoclopramide or haloperidol with or without additional lorazepam until relief |
| Improvement in Nausea Score From Baseline to 12 Hours | Baseline to 12 hours after study drug administered. | The outcome measure is the number of participants that self report improvement in a nausea score from baseline, prior to fosaprepitant, to 12 hours post dose. This includes only participants who report breakthrough nausea or vomiting after chemotherapy and after receiving prophylactic anti-emetics. The primary outcome is measured using the visual analogue scale, a self report scale from No Nausea to Nausea as bad as it can be; a value can be indicated anywhere on this scale using a free hand mark by the participant and gauged with ruler by study staff. Any participant that reported a lower value on the scale 12 hours from baseline would be considered in this outcome measure. |
| Participants With Increased Fatigue or Sedation Within 24 Hours After Receiving Fosaprepitant | up to 24 hours after study drug administered. | Participants meeting this outcome self report experiencing drowsiness at any of the study time points (2, 12 or 24 hours after receiving fosaprepitant). |
| Participants With Specific Side Effects, Including Pain Sensation/Soreness at the Infusion Site, Headache, and Dizziness | up to 24 hours after study drug administered. | Participants who self report pain/soreness at drug infusion site, headache, or dizziness at any of the study time points (2, 12, or 24 hours after receiving fosaprepitant) are measured in this outcome. |
| Participants Achieving a Complete Response (no Emesis, no Additional Rescue Medication Required) | up to 24 hours after receiving fosaprepitant | The recommended dose Fosaprepitant (MK-0517) is 115 mg administered intravenously 30 minutes before chemotherapy treatment. In this study, a 150 mg dose will be given to study patients as rescue therapy after chemotherapy only in the event of breakthrough nausea or vomiting. Those participants who did not report episodes of emesis or did not require additional rescue medications are measured in this outcome |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from August 2008 until January 2013
Pre-assignment details
There were 34 participants who signed the informed consent for this study but of these, only 11 received the study treatment. The other 23 were screen failures.
Participants by arm
| Arm | Count |
|---|---|
| Fosaprepitant | 11 |
| Total | 11 |
Baseline characteristics
| Characteristic | Fosaprepitant |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants |
| Age, Continuous | 45 years STANDARD_DEVIATION 12 |
| Region of Enrollment United States | 11 participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 7 / 11 |
| serious Total, serious adverse events | 0 / 11 |
Outcome results
Primary
Improvement in Nausea Score From Baseline to 2 Hours as Assessed by the Numerical Visual Analogue Scale
The outcome measure is the number of participants that self report improvement in a nausea score from baseline, prior to fosaprepitant, to 2 hours post dose. This includes only participants who report breakthrough nausea or vomiting after chemotherapy and after receiving prophylactic anti-emetics. The primary outcome is measured using the visual analogue scale, a self report scale from No Nausea to Nausea as bad as it can be; a value can be indicated anywhere on this scale using a free hand mark by the participant and gauged with ruler by study staff. Any participant that reported a lower value on the scale 2 hours from baseline would be considered in this outcome measure.
Time frame: Baseline to 2 hours after study drug administered.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Participants Receiving Fosaprepitant | Improvement in Nausea Score From Baseline to 2 Hours as Assessed by the Numerical Visual Analogue Scale | 10 participants |
Secondary
Improvement in Nausea Score From 2 Hours to 24 Hours
The outcome measure is the number of participants that self report improvement in a nausea score from 2 hours after receiving fosaprepitant to 24 hours post dose. This includes only participants who report breakthrough nausea or vomiting after chemotherapy and after receiving prophylactic anti-emetics. The outcome is measured using the visual analogue scale, a self report scale from No Nausea to Nausea as bad as it can be; a value can be indicated anywhere on this scale using a free hand mark by the participant and gauged with ruler by study staff. Any participant reporting a lower value on the scale at the 12 or 24 hour time point would be considered in this outcome measure.
Time frame: 2 hours to 24 hours after study drug administered.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Participants Receiving Fosaprepitant | Improvement in Nausea Score From 2 Hours to 24 Hours | 7 participants |
Secondary
Improvement in Nausea Score From Baseline to 12 Hours
The outcome measure is the number of participants that self report improvement in a nausea score from baseline, prior to fosaprepitant, to 12 hours post dose. This includes only participants who report breakthrough nausea or vomiting after chemotherapy and after receiving prophylactic anti-emetics. The primary outcome is measured using the visual analogue scale, a self report scale from No Nausea to Nausea as bad as it can be; a value can be indicated anywhere on this scale using a free hand mark by the participant and gauged with ruler by study staff. Any participant that reported a lower value on the scale 12 hours from baseline would be considered in this outcome measure.
Time frame: Baseline to 12 hours after study drug administered.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Participants Receiving Fosaprepitant | Improvement in Nausea Score From Baseline to 12 Hours | 11 participants |
Secondary
Number of Participants Who Experienced Vomiting Episodes From Baseline to 24 Hours
Participants were asked to report any episodes of vomiting before (baseline) and up to 24 hours after receiving Fosaprepitant. The outcome considers the number of participants reporting any episodes of emesis after receiving Fosaprepitant.
Time frame: Baseline to 24 hours after study drug administered.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Participants Receiving Fosaprepitant | Number of Participants Who Experienced Vomiting Episodes From Baseline to 24 Hours | 2 participants |
Secondary
Participants Achieving a Complete Response (no Emesis, no Additional Rescue Medication Required)
The recommended dose Fosaprepitant (MK-0517) is 115 mg administered intravenously 30 minutes before chemotherapy treatment. In this study, a 150 mg dose will be given to study patients as rescue therapy after chemotherapy only in the event of breakthrough nausea or vomiting. Those participants who did not report episodes of emesis or did not require additional rescue medications are measured in this outcome
Time frame: up to 24 hours after receiving fosaprepitant
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Participants Receiving Fosaprepitant | Participants Achieving a Complete Response (no Emesis, no Additional Rescue Medication Required) | 1 participants |
Secondary
Participants Who Required the Use of Second Rescue Drug (Time to Treatment Failure)
Participants with persistent nausea/vomiting after 2 hours and who desired further treatment, received standard rescue therapy at the discretion of provider with prochlorperazine, metoclopramide or haloperidol with or without additional lorazepam until relief
Time frame: 2 hours after administration of Fosaprepitant 150 mg IV
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Participants Receiving Fosaprepitant | Participants Who Required the Use of Second Rescue Drug (Time to Treatment Failure) | 9 participants |
Secondary
Participants With Increased Fatigue or Sedation Within 24 Hours After Receiving Fosaprepitant
Participants meeting this outcome self report experiencing drowsiness at any of the study time points (2, 12 or 24 hours after receiving fosaprepitant).
Time frame: up to 24 hours after study drug administered.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Participants Receiving Fosaprepitant | Participants With Increased Fatigue or Sedation Within 24 Hours After Receiving Fosaprepitant | 7 participants |
Secondary
Participants With Specific Side Effects, Including Pain Sensation/Soreness at the Infusion Site, Headache, and Dizziness
Participants who self report pain/soreness at drug infusion site, headache, or dizziness at any of the study time points (2, 12, or 24 hours after receiving fosaprepitant) are measured in this outcome.
Time frame: up to 24 hours after study drug administered.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Participants Receiving Fosaprepitant | Participants With Specific Side Effects, Including Pain Sensation/Soreness at the Infusion Site, Headache, and Dizziness | 5 participants |