Nausea, Vomiting
Conditions
Keywords
nausea, vomiting
Brief summary
RATIONALE: Ginger may help reduce or prevent nausea. It is not yet known if antiemetic drugs are more effective with or without ginger in treating nausea caused by chemotherapy. PURPOSE: This randomized phase II/III trial is studying giving antiemetic drugs together with ginger to see how well they work compared to antiemetic drugs alone in treating nausea in patients who are receiving chemotherapy for cancer.
Detailed description
OBJECTIVES: * Compare the efficacy of 1 course of ginger vs placebo when administered in regimens containing a 5-hydroxytryptamine type 3 (5-HT3) receptor antagonist antiemetic and dexamethasone (or the equivalent dose of IV methylprednisolone) in controlling chemotherapy-related nausea at course 2 of chemotherapy in patients with cancer. * Compare the efficacy of 3 different doses of ginger in controlling chemotherapy-related nausea in these patients. * Determine the adverse effects of ginger when given 3 days before chemotherapy administration in these patients. * Determine the adverse effects of these antiemetic regimens during the 4 days after chemotherapy. * Compare the chemotherapy-related anticipatory nausea in patients treated with these antiemetic regimens. * Compare the quality of life during the 4 days after chemotherapy in patients treated with these antiemetic regimens. * Compare the chemotherapy-related nausea at course 3 of chemotherapy in these patients after 2 courses of ginger vs placebo. OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to participating center. Patients are randomized to 1 of 4 treatment arms. Day 1 of each course is defined as the day of chemotherapy administration. * Placebo: Patients receive oral placebo twice daily on days -3 to 3 of chemotherapy courses 2 and 3. * 0.5g Ginger: Patients receive oral low-dose ginger and oral placebo twice daily on days -3 to 3 of chemotherapy courses 2 and 3. * 1.0g Ginger: Patients receive oral intermediate-dose ginger and oral placebo twice daily on days -3 to 3 of chemotherapy courses 2 and 3. * 1.5g Ginger: Patients receive oral high-dose ginger twice daily on days -3 to 3 of chemotherapy courses 2 and 3. Patients in each arm also continue receiving their scheduled antiemetic regimen comprising a 5-hydroxytryptamine type-3 (5-HT3) receptor antagonist (ondansetron, granisetron, tropisetron, and dolasetron mesylate) and dexamethasone (DM) (or the equivalent dose of IV methylprednisolone (MePRDL)) on day 1 of courses 2 and 3. Symptoms are assessed on day -3 to day 1 of courses 2 and 3 and on days 1-4 of courses 1-3. Quality of life is assessed on day 4 of courses 1-3. Nausea and vomiting are assessed 4 times daily on days 1-4 of courses 1-3. PROJECTED ACCRUAL: A total of 706 patients will be accrued for this study within 3 years.
Interventions
DIETARY_SUPPLEMENTginger
Given orally
OTHERplacebo
Given orally
Sponsors
National Cancer Institute (NCI)
Gary Morrow
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Diagnosis of cancer and be scheduled to receive at least 3 courses of chemotherapy * Scheduled to receive chemotherapy with no planned interruption by radiotherapy or surgery * Chemotherapy courses must be separated by at least 2 weeks from day 1 to day 1 of next course * Must have experienced nausea of any degree of severity after completion of the first study-related course of chemotherapy * Received a prior 5-hydroxytryptamine type 3 (5-HT3) receptor antagonist antiemetic (ondansetron, granisetron, tropisetron, or dolasetron mesylate) with dexamethasone (DM) given at any dose and by any route (or equivalent dose of IV methylprednisolone (MePRDL)) on day 1 of course 1 of chemotherapy * Scheduled to receive a 5-HT3 receptor antagonist antiemetic with DM (or equivalent dose of IV MePRDL) on day 1 of courses 2 and 3 of chemotherapy * No symptomatic brain metastases PATIENT CHARACTERISTICS: Age: * 18 and over Performance status: * Not specified Life expectancy: * Not specified Hematopoietic: * Platelet count greater than 100,000/mm\^3 at second course of chemotherapy * No prior bleeding or blood coagulation disorder (e.g., thrombocytopenia or platelet dysfunction) Hepatic: * No prior coagulation factor deficiency Renal: * Not specified Cardiovascular: * No prior vascular defect Other: * Able to understand English * No concurrent or impending bowel obstruction PRIOR CONCURRENT THERAPY: Biologic therapy: * No concurrent interferon therapy Chemotherapy: * See Disease Characteristics * At least 6 months since other prior chemotherapy Endocrine therapy: * Not specified Radiotherapy: * See Disease Characteristics * No concurrent radiotherapy Surgery: * See Disease Characteristics Other: * No concurrent warfarin or heparin for therapeutic anticoagulation * Concurrent low-dose warfarin for maintenance of venous access allowed * Concurrent rescue medications for control of symptoms caused by the cancer or its treatment allowed as clinically indicated
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline of Peak Acute Nausea | 3-4 days on study drug | Nausea evaluated on a 7-point semantic rating scale anchored by 1 = Not at all nauseated and by 7 = Extremely nauseated. Acute nausea calculated as the maximum of the Day 1 Evening and Night nausea ratings. Change from post-intervention (cycle 2 of chemotherapy) - baseline (cycle 1 of chemotherapy) of peak acute nausea used as the outcome measure. Negative values for this outcome are favorable. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Average Nausea Severity | 3-4 days on study drug | Nausea evaluated on a 7-point semantic rating scale anchored by 1 = Not at all nauseated and by 7 = Extremely nauseated. Acute nausea calculated as the average of the Day 1 Evening and Night nausea ratings. Change from post-intervention (cycle 2 of chemotherapy) - baseline (cycle 1 of chemotherapy) of average acute nausea used as the outcome measure. Negative values for this outcome are favorable. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Patients receive oral placebo twice daily on days -3 to 3 of chemotherapy courses 2 and 3.
placebo: Given orally | 149 |
| 0.5g Ginger Patients receive oral low-dose ginger and oral placebo twice daily on days -3 to 3 of chemotherapy courses 2 and 3.
ginger extract: Given orally
placebo: Given orally | 134 |
| 1.0g Ginger Patients receive oral intermediate-dose ginger and oral placebo twice daily on days -3 to 3 of chemotherapy courses 2 and 3.
ginger extract: Given orally
placebo: Given orally | 141 |
| 1.5g Ginger Patients receive oral high-dose ginger twice daily on days -3 to 3 of chemotherapy courses 2 and 3.
ginger extract: Given orally | 152 |
| Total | 576 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 15 | 16 | 21 | 9 |
| Overall Study | Chemotoxicity | 4 | 3 | 5 | 2 |
| Overall Study | Death | 0 | 0 | 1 | 0 |
| Overall Study | Incomplete Forms | 6 | 10 | 4 | 5 |
| Overall Study | Other medical | 7 | 5 | 5 | 5 |
| Overall Study | Withdrawal by Subject | 7 | 15 | 10 | 13 |
Baseline characteristics
| Characteristic | Total | 1.5g Ginger | Placebo | 0.5g Ginger | 1.0g Ginger |
|---|---|---|---|---|---|
| Age, Continuous | 52.75 years STANDARD_DEVIATION 10.68 | 52 years STANDARD_DEVIATION 9.86 | 53 years STANDARD_DEVIATION 10.62 | 54 years STANDARD_DEVIATION 11.58 | 52 years STANDARD_DEVIATION 10.69 |
| Baseline average nausea, Day1 | 2.4 units on a scale STANDARD_DEVIATION 1.8 | 2.4 units on a scale STANDARD_DEVIATION 1.7 | 2.2 units on a scale STANDARD_DEVIATION 1.6 | 2.6 units on a scale STANDARD_DEVIATION 1.9 | 2.5 units on a scale STANDARD_DEVIATION 1.8 |
| Baseline nausea at its worst | 2.7 units on a scale STANDARD_DEVIATION 2 | 2.7 units on a scale STANDARD_DEVIATION 2 | 2.5 units on a scale STANDARD_DEVIATION 1.7 | 2.9 units on a scale STANDARD_DEVIATION 2.1 | 2.8 units on a scale STANDARD_DEVIATION 2 |
| Education College Grad | 216 participants | 54 participants | 60 participants | 47 participants | 55 participants |
| Education H.S. Grad | 336 participants | 95 participants | 82 participants | 78 participants | 81 participants |
| Education Some/No HS | 23 participants | 3 participants | 6 participants | 9 participants | 5 participants |
| Education Unknown | 1 participants | 0 participants | 1 participants | 0 participants | 0 participants |
| Marital status Married | 420 participants | 114 participants | 107 participants | 96 participants | 103 participants |
| Marital status Not Married | 156 participants | 38 participants | 42 participants | 38 participants | 38 participants |
| Previous chemotherapy No | 251 participants | 70 participants | 68 participants | 57 participants | 56 participants |
| Previous chemotherapy Unknown | 2 participants | 0 participants | 0 participants | 2 participants | 0 participants |
| Previous chemotherapy Yes | 323 participants | 82 participants | 81 participants | 75 participants | 85 participants |
| Previous radiation therapy No | 533 participants | 144 participants | 136 participants | 125 participants | 128 participants |
| Previous radiation therapy Unknown | 2 participants | 0 participants | 0 participants | 2 participants | 0 participants |
| Previous radiation therapy Yes | 41 participants | 8 participants | 13 participants | 7 participants | 13 participants |
| Previous surgery No | 75 participants | 23 participants | 18 participants | 19 participants | 15 participants |
| Previous surgery Yes | 501 participants | 129 participants | 131 participants | 115 participants | 126 participants |
| Quality of life(FACT-G) | 72 units on a scale STANDARD_DEVIATION 15.6 | 72 units on a scale STANDARD_DEVIATION 16 | 72 units on a scale STANDARD_DEVIATION 15.9 | 72 units on a scale STANDARD_DEVIATION 15 | 71 units on a scale STANDARD_DEVIATION 15.4 |
| Race/Ethnicity, Customized Non-White | 36 participants | 10 participants | 11 participants | 8 participants | 7 participants |
| Race/Ethnicity, Customized Unknown | 2 participants | 0 participants | 1 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized White | 538 participants | 142 participants | 137 participants | 126 participants | 133 participants |
| Sex: Female, Male Female | 521 Participants | 142 Participants | 135 Participants | 122 Participants | 122 Participants |
| Sex: Female, Male Male | 55 Participants | 10 Participants | 14 Participants | 12 Participants | 19 Participants |
| Tumor site Alimentary | 43 participants | 8 participants | 14 participants | 11 participants | 10 participants |
| Tumor site Breast | 427 participants | 117 participants | 107 participants | 100 participants | 103 participants |
| Tumor site Genitourinary | 10 participants | 2 participants | 2 participants | 3 participants | 3 participants |
| Tumor site Gynecologic | 31 participants | 5 participants | 11 participants | 6 participants | 9 participants |
| Tumor site Hematologic | 24 participants | 8 participants | 3 participants | 4 participants | 9 participants |
| Tumor site Lung | 33 participants | 10 participants | 10 participants | 7 participants | 6 participants |
| Tumor site Other | 8 participants | 2 participants | 2 participants | 3 participants | 1 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 5 / 188 | 7 / 183 | 3 / 187 | 8 / 187 |
| serious Total, serious adverse events | 0 / 188 | 0 / 183 | 1 / 187 | 0 / 187 |
Outcome results
Primary
Change From Baseline of Peak Acute Nausea
Nausea evaluated on a 7-point semantic rating scale anchored by 1 = Not at all nauseated and by 7 = Extremely nauseated. Acute nausea calculated as the maximum of the Day 1 Evening and Night nausea ratings. Change from post-intervention (cycle 2 of chemotherapy) - baseline (cycle 1 of chemotherapy) of peak acute nausea used as the outcome measure. Negative values for this outcome are favorable.
Time frame: 3-4 days on study drug
Population: Eligible patients 18 years of age or older, able to understand English, diagnosed with cancer, may have received more than one chemotherapy cycle and scheduled for at least three additional cycles; randomization stratified by CCOP site. A computer-generated random numbers table assigned patients to one of four treatment arms.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline of Peak Acute Nausea | 0.03 units on a scale | Standard Deviation 1.85 |
| 0.5g Ginger | Change From Baseline of Peak Acute Nausea | -0.56 units on a scale | Standard Deviation 1.83 |
| 1.0g Ginger | Change From Baseline of Peak Acute Nausea | -0.44 units on a scale | Standard Deviation 1.79 |
| 1.5g Ginger | Change From Baseline of Peak Acute Nausea | -0.15 units on a scale | Standard Deviation 1.82 |
Comparison: H0: Mean difference between 0.5g and placebo of change from baseline of Peak Acute Nausea = 0.~Ha: Mean difference between 0.5g and placebo of change from baseline of Peak Acute Nausea \> 0. (Two-sided)p-value: 0.017Mixed Models Analysis
Comparison: H0: Mean difference between 1.0g and placebo of change from baseline of Peak Acute Nausea = 0.~Ha: Mean difference between 1.0g and placebo of change from baseline of Peak Acute Nausea \> 0. (Two-sided)p-value: 0.036Mixed Models Analysis
Comparison: H0: Mean difference between 1.5g and placebo of change from baseline of Peak Acute Nausea = 0.~Ha: Mean difference between 1.5g and placebo of change from baseline of Peak Acute Nausea \> 0. (Two-sided)p-value: 0.431Mixed Models Analysis
Comparison: Placebo vs. Any Ginger. H0: Mean difference between \[(0.5g +1.0g +1.5g) / 3\] and placebo of change from baseline of Peak Acute Nausea = 0.~Ha: Mean difference between \[(0.5g +1.0g +1.5g) / 3\] and placebo of change from baseline of Peak Acute Nausea \> 0. (Two-sided)p-value: 0.003Mixed Models Analysis
Secondary
Average Nausea Severity
Nausea evaluated on a 7-point semantic rating scale anchored by 1 = Not at all nauseated and by 7 = Extremely nauseated. Acute nausea calculated as the average of the Day 1 Evening and Night nausea ratings. Change from post-intervention (cycle 2 of chemotherapy) - baseline (cycle 1 of chemotherapy) of average acute nausea used as the outcome measure. Negative values for this outcome are favorable.
Time frame: 3-4 days on study drug
Population: Eligible patients 18 years of age or older, able to understand English, diagnosed with cancer, may have received more than one chemotherapy cycle and scheduled for at least three additional cycles; randomization stratified by CCOP site. A computer-generated random numbers table assigned patients to one of four treatment arms.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Average Nausea Severity | 0.03 units on a scale | Standard Error 1.58 |
| 0.5g Ginger | Average Nausea Severity | -0.44 units on a scale | Standard Error 1.67 |
| 1.0g Ginger | Average Nausea Severity | -0.34 units on a scale | Standard Error 1.64 |
| 1.5g Ginger | Average Nausea Severity | -0.05 units on a scale | Standard Error 1.68 |
Comparison: H0: Mean difference between 0.5g and placebo of change from baseline of Average Acute Nausea = 0.~Ha: Mean difference between 0.5g and placebo of change from baseline of Average Acute Nausea \> 0. (Two-sided)p-value: 0.046Mixed Models Analysis
Comparison: H0: Mean difference between 1.0g and placebo of change from baseline of Average Acute Nausea = 0.~Ha: Mean difference between 1.0g and placebo of change from baseline of Average Acute Nausea \> 0. (Two-sided)p-value: 0.076Mixed Models Analysis
Comparison: H0: Mean difference between 1.5g and placebo of change from baseline of Average Acute Nausea = 0.~Ha: Mean difference between 1.5g and placebo of change from baseline of Average Acute Nausea \> 0. (Two-sided)p-value: 0.738Mixed Models Analysis
Comparison: Placebo vs Any Ginger. H0: Mean difference between \[(0.5g +1.0g +1.5g) / 3\] and placebo of change from baseline of Average Acute Nausea = 0.~Ha: Mean difference between \[(0.5g +1.0g +1.5g) / 3\] and placebo of change from baseline of Average Acute Nausea \> 0. (Two-sided)p-value: 0.013Mixed Models Analysis