A Phase 3 interventional study of Palonosetron Hydrochloride and Ondansetron Hydrochloride in Malignant Neoplasm, sponsored by Alliance for Clinical Trials in Oncology. Completed at 566 sites in 2 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-04-06.
Sponsored by Alliance for Clinical Trials in Oncology · Phase 3, Interventional, and Supportive care
This randomized phase III trial studies how well olanzapine with or without fosaprepitant work in preventing chemotherapy induced nausea and vomiting in cancer patients receiving chemotherapy that causes vomiting. Olanzapine and fosaprepitant dimeglumine may help control nausea and vomiting in patients during chemotherapy. Olanzapine is usually given in combination with other drugs, including fosaprepitant dimeglumine. It is not yet known if olanzapine when given with other drugs, is still effective without using fosaprepitant dimeglumine for controlling nausea and vomiting.
PRIMARY OBJECTIVES:
I. To compare between the two study arms the proportion of patients with no nausea for the overall (0-120 hours post-chemotherapy), acute (0-24 hours post-chemotherapy), and delayed periods (24-120 hours post-chemotherapy) for patients receiving highly emetogenic chemotherapy (HEC).
SECONDARY OBJECTIVES:
I. To compare between the two study arms the complete response (CR) rates (no emetic episodes and no use of rescue medication) in the acute, delayed, and overall periods.
II. To compare between the two study arms, the incidences of potential toxicities that have been ascribed to olanzapine.
III. To perform an economic evaluation of olanzapine and fosaprepitant dimeglumine (fosaprepitant) versus (vs.) olanzapine in patients receiving HEC (noting that all patients will also receive dexamethasone and a 5HT3 receptor antagonist).
IV. To explore the efficacy of olanzapine in chemotherapy cycles two to four, for patients who elect to continue on the same antiemetic regimen received in cycle one, in chemotherapy cycles two to four (continuation phase), by documenting nausea and complete response.
V. To explore the safety of olanzapine in chemotherapy cycles two to four, for patients who elect to continue on the same antiemetic regimen received in cycle one, in chemotherapy cycles two to four (continuation phase), by recording any adverse events or drug related toxicities.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Patients receive palonosetron hydrochloride intravenously (IV) over 30 seconds or ondansetron hydrochloride IV over 2-5 minutes or orally (PO) on day 1, dexamethasone PO on days 1-4, fosaprepitant dimeglumine IV over 20-30 minutes on day 1, and olanzapine PO on days 1-4. Treatment may repeat every 4 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive palonosetron hydrochloride IV over 30 seconds or ondansetron hydrochloride IV over 2-5 minutes or PO on day 1, dexamethasone PO on days 1-4, placebo IV over 20-30 minutes on day 1, and olanzapine PO on days 1-4. Treatment (with no placebo) may repeat every 4 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.
After completion of study, patients are followed up periodically.
10,818 studies on the registry are indexed under Neoplasms; 2,324 are open to participants now.
This study's enrollment of 690 is above the median of 60 across 7,703 interventional studies indexed under Neoplasms.
Browse Neoplasms studies →Alliance for Clinical Trials in Oncology is the lead sponsor of 509 studies on the registry; 28 are open to participants now.
Of its 6 completed or terminated interventional studies of FDA-regulated products, 6 (100%) have results posted.
Counted across the registry records on this site, refreshed daily.
Inclusion Criteria:
Negative pregnancy test (serum or urine) done =\< 7 days prior to registration, for women of only
* A female of childbearing potential is a sexually mature female who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months)
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Cancer deposits in the brain from a cancer that started elsewhere in the body (CNS metastases include the spinal cord).
Studies differ: some leave out any brain metastases, some accept ones treated and stable for some weeks. Check what this study allows.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Postmenopausal
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Brain metastases
Cancer deposits in the brain from a cancer that started elsewhere in the body (CNS metastases include the spinal cord).
Studies differ: some leave out any brain metastases, some accept ones treated and stable for some weeks. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECOG performance status
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Patients receive palonosetron hydrochloride IV over 30 seconds or ondansetron hydrochloride IV over 2-5 minutes or PO on day 1, dexamethasone PO on days 1-4, fosaprepitant dimeglumine IV over 20-30 minutes on day 1, and olanzapine PO on days 1-4. Treatment may repeat every 4 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.
Drug: Palonosetron Hydrochloride · Drug: Ondansetron Hydrochloride · Drug: Dexamethasone · Drug: Fosaprepitant Dimeglumine · Drug: Olanzapine
Patients receive palonosetron hydrochloride IV over 30 seconds or ondansetron hydrochloride IV over 2-5 minutes or PO on day 1, dexamethasone PO on days 1-4, placebo IV over 20-30 minutes on day 1, and olanzapine PO on days 1-4. Treatment (with no placebo) may repeat every 4 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.
Drug: Palonosetron Hydrochloride · Drug: Ondansetron Hydrochloride · Drug: Dexamethasone · Drug: Olanzapine · Other: Placebo
Given IV
Given IV or PO
Given PO
Given IV
Given PO
Given IV
No Nausea Rate Defined as a Response of 0 in the Nausea Item of Nausea and Vomiting Daily Diary/Questionnaire in the Overall (0-120 Hours), Acute (0-24 Hours), and Delayed (24-120 Hours) Periods
The specific measure will be based on the proportion of patients with a value of 0, as measured by the single nausea item (scale 0-10, 0 is no symptoms, 10 is worst symptoms) of the Questionnaire. A modified intent-to-treat principle will be applied for statistical analysis of efficacy in evaluable patients. The proportions of patients with no nausea during the overall, the acute, and the delayed period will be summarized by treatment arm. They will be tested in a sequential manner, using a Simes gatekeeping procedure to maintain the overall significance level at the specified by the Lan-DeMets family of alpha spending function. The difference in no nausea proportions between arms will be estimated along with a one-sided 95% confidence interval. The tests and the confidence intervals will be constructed using normal approximation of the binomial distribution adjusted for the non-inferiority margin.
Time frame: Up to 120 hours
Complete Response (CR) (no Emetic Episodes and no Use of Rescue Medication) During the Acute, Delayed and the Overall Periods as Measured by the Nausea and Vomiting Daily Diary/Questionnaire
The specific measure will be based on the proportion of patients who answered "None" to both questions concerning Vomiting episode(None, Once, Twice, More than twice) and number of extra nausea/vomiting pills taken (None, One, Two, More than two) in the Nausea and Vomiting Daily Diary/Questionnaire. The CR rate for the overall, the acute, and the delayed period will be summarized by treatment arm and will be compared using a Chi-squared test. The difference in CR rates between arms will be estimated along with a 95% confidence interval.
Time frame: Up to 120 hours
Potential Toxicities as Ascribed to Olanzapine as Measured by the Nausea and Vomiting Daily Diary/Questionnaire
Potential toxicities includes nausea, undesired sedation, and undesired appetite, measured by three individual items ( nausea, undesired sedation, undesired appetite) of the Nausea and Vomiting Daily Dairy/Questionnaire(scale 0-10, 0 is no symptoms, 10 is worst symptoms). Incidences of toxicities will be summarized by type and by treatment arm. Incidences of toxicities will be compared between arms using a Chi-squared test or the Fisher's exact test as appropriate. In addition, undesired sedation and appetite increase as collected in the Nausea and Vomiting Daily Diary/Questionnaire will be analyzed by repeated measures analyses including descriptive statistics, graphical approaches, and growth curve models to account for the factor of day and time trend.
Time frame: Up to 120 hours
Average Nausea Scores (0-10) Repeatedly Measured by the Nausea and Vomiting Daily Diary/Questionnaire
The specific measure will be based on the by the single nausea item (scale 0-10, 0 is no symptoms, 10 is worst symptoms) of the Nausea and Vomiting Daily Diary/Questionnaire. Nausea scores (0-10) repeatedly measured by the Nausea and Vomiting Daily Diary/Questionnaire will be analyzed using the repeated measures analyses and growth curve models as described above for undesired sedation and increase in appetite.
Time frame: Up to 1 year
Total Frequency of Rescue Medication as Measured by the Nausea and Vomiting Daily Diary/Questionnaire
The specific measure will be based on the single item : number of extra nausea/vomiting pills taken (None, One , Twice, More than twice) of the Nausea and Vomiting Daily Diary/Questionnaire.
Time frame: Over 5 Days per each of the 4 cycles
| Milestone | Arm I (Fosaprepitant Dimeglumine, Olanzapine) | Arm II (Placebo, Olanzapine) |
|---|---|---|
| Started | 346 | 344 |
| Completed | 326 | 320 |
| Not completed | 20 | 24 |
The specific measure will be based on the proportion of patients with a value of 0, as measured by the single nausea item (scale 0-10, 0 is no symptoms, 10 is worst symptoms) of the Questionnaire. A modified intent-to-treat principle will be applied for statistical analysis of efficacy in evaluable patients. The proportions of patients with no nausea during the overall, the acute, and the delayed period will be summarized by treatment arm. They will be tested in a sequential manner, using a Simes gatekeeping procedure to maintain the overall significance level at the specified by the Lan-DeMets family of alpha spending function. The difference in no nausea proportions between arms will be estimated along with a one-sided 95% confidence interval. The tests and the confidence intervals will be constructed using normal approximation of the binomial distribution adjusted for the non-inferiority margin.
| Participants | Arm I (Fosaprepitant Dimeglumine, Olanzapine) | Arm II (Placebo, Olanzapine) |
|---|---|---|
| Overall No Nausea | 123 | 97 |
| Overall Any Nausea | 203 | 223 |
| Acute No Nausea | 202 | 201 |
| Acute Any Nausea | 124 | 119 |
| Delayed No Nausea | 140 | 114 |
| Delayed Any Nausea | 186 | 206 |
The specific measure will be based on the proportion of patients who answered "None" to both questions concerning Vomiting episode(None, Once, Twice, More than twice) and number of extra nausea/vomiting pills taken (None, One, Two, More than two) in the Nausea and Vomiting Daily Diary/Questionnaire. The CR rate for the overall, the acute, and the delayed period will be summarized by treatment arm and will be compared using a Chi-squared test. The difference in CR rates between arms will be estimated along with a 95% confidence interval.
| Participants | Arm I (Fosaprepitant Dimeglumine, Olanzapine) | Arm II (Placebo, Olanzapine) |
|---|---|---|
| Complete Response - >> Overall | 179 | 151 |
| Complete Response - >> Acute | 256 | 247 |
| Complete Response ->> Delayed | 193 | 166 |
Potential toxicities includes nausea, undesired sedation, and undesired appetite, measured by three individual items ( nausea, undesired sedation, undesired appetite) of the Nausea and Vomiting Daily Dairy/Questionnaire(scale 0-10, 0 is no symptoms, 10 is worst symptoms). Incidences of toxicities will be summarized by type and by treatment arm. Incidences of toxicities will be compared between arms using a Chi-squared test or the Fisher's exact test as appropriate. In addition, undesired sedation and appetite increase as collected in the Nausea and Vomiting Daily Diary/Questionnaire will be analyzed by repeated measures analyses including descriptive statistics, graphical approaches, and growth curve models to account for the factor of day and time trend.
| Participants | Arm I (Fosaprepitant Dimeglumine, Olanzapine) | Arm II (Placebo, Olanzapine) |
|---|---|---|
| Overall No Appetite Increase | 140 | 136 |
| Overall Any Appetite Increase | 186 | 184 |
| Acute No Appetite Increase | 235 | 236 |
| Acute Any Appetite Increase | 91 | 84 |
| Delayed No Appetite Increase | 147 | 143 |
| Delayed Any Appetite Increase | 179 | 177 |
The specific measure will be based on the by the single nausea item (scale 0-10, 0 is no symptoms, 10 is worst symptoms) of the Nausea and Vomiting Daily Diary/Questionnaire. Nausea scores (0-10) repeatedly measured by the Nausea and Vomiting Daily Diary/Questionnaire will be analyzed using the repeated measures analyses and growth curve models as described above for undesired sedation and increase in appetite.
| score on a scale | Arm I (Fosaprepitant Dimeglumine, Olanzapine) | Arm II (Placebo, Olanzapine) |
|---|---|---|
| Average Nausea Scores (0-10) Repeatedly Measured by the Nausea and Vomiting Daily Diary/Questionnaire | 0.8211364 ± 1.6289005 | 0.9177778 ± 1.7821806 |
The specific measure will be based on the single item : number of extra nausea/vomiting pills taken (None, One , Twice, More than twice) of the Nausea and Vomiting Daily Diary/Questionnaire.
| episodes | Arm I (Fosaprepitant Dimeglumine, Olanzapine) | Arm II (Placebo, Olanzapine) |
|---|---|---|
| Zero | 3614 | 3541 |
| One | 350 | 405 |
| Two | 170 | 162 |
| More than two | 56 | 74 |
Collected over Up to 1 year. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Arm I (Fosaprepitant Dimeglumine, Olanzapine) | 1/286 (0.3%) | 51/286 (17.8%) | 252/286 (88.1%) |
| Arm II (Placebo, Olanzapine) | 2/291 (0.7%) | 60/291 (20.6%) | 248/291 (85.2%) |
| Event | Arm I (Fosaprepitant Dimeglumine, Olanzapine) | Arm II (Placebo, Olanzapine) |
|---|---|---|
| Neutrophil count decreasedInvestigations | 9/286 | 10/291 |
| White blood cell decreasedInvestigations | 5/286 | 7/291 |
| AnemiaBlood and lymphatic system disorders | 4/286 | 1/291 |
| Febrile neutropeniaBlood and lymphatic system disorders | 2/286 | 3/291 |
| SepsisInfections and infestations | 2/286 | 3/291 |
| Creatinine increasedInvestigations | 0/286 | 3/291 |
| HypokalemiaMetabolism and nutrition disorders | 0/286 | 3/291 |
| HypotensionVascular disorders | 2/286 | 3/291 |
| Lymphocyte count decreasedInvestigations | 2/286 | 2/291 |
| DehydrationMetabolism and nutrition disorders | 2/286 | 2/291 |
| Event | Arm I (Fosaprepitant Dimeglumine, Olanzapine) | Arm II (Placebo, Olanzapine) |
|---|---|---|
| FatigueGeneral disorders | 19/286 | 22/291 |
| Lymphocyte count decreasedInvestigations | 20/286 | 17/291 |
| Neutrophil count decreasedInvestigations | 20/286 | 19/291 |
| AlopeciaSkin and subcutaneous tissue disorders | 14/286 | 20/291 |
| AnemiaBlood and lymphatic system disorders | 13/286 | 18/291 |
| White blood cell decreasedInvestigations | 11/286 | 17/291 |
| SomnolenceNervous system disorders | 11/286 | 15/291 |
| HypoalbuminemiaMetabolism and nutrition disorders | 7/286 | 1/291 |
| Platelet count decreasedInvestigations | 3/286 | 7/291 |
| Gastroesophageal reflux diseaseGastrointestinal disorders | 6/286 | 2/291 |
| Age, Continuous(years) | Arm I (Fosaprepitant Dimeglumine, Olanzapine) | Arm II (Placebo, Olanzapine) | Total |
|---|---|---|---|
| Mean | 56.5 ± 11.10 | 56.1 ± 11.58 | 56.3 ± 11.34 |
| Sex: Female, Male(Participants) | Arm I (Fosaprepitant Dimeglumine, Olanzapine) | Arm II (Placebo, Olanzapine) | Total |
|---|---|---|---|
| Female | 289 | 289 | 578 |
| Male | 57 | 55 | 112 |
| Ethnicity (NIH/OMB)(Participants) | Arm I (Fosaprepitant Dimeglumine, Olanzapine) | Arm II (Placebo, Olanzapine) | Total |
|---|---|---|---|
| Hispanic or Latino | 3 | 7 | 10 |
| Not Hispanic or Latino | 331 | 325 | 656 |
| Unknown or Not Reported | 12 | 12 | 24 |
| Race (NIH/OMB)(Participants) | Arm I (Fosaprepitant Dimeglumine, Olanzapine) | Arm II (Placebo, Olanzapine) | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 2 | 2 |
| Asian | 4 | 12 | 16 |
| Native Hawaiian or Other Pacific Islander | 1 | 0 | 1 |
| Black or African American | 36 | 40 | 76 |
| White | 292 | 278 | 570 |
| More than one race | 1 | 1 | 2 |
| Unknown or Not Reported | 12 | 11 | 23 |
| ECOG Performance Score(Participants) | Arm I (Fosaprepitant Dimeglumine, Olanzapine) | Arm II (Placebo, Olanzapine) | Total |
|---|---|---|---|
| 0 | 276 | 281 | 557 |
| 1 | 67 | 59 | 126 |
| 2 | 3 | 4 | 7 |
| Chemotherapy Regimen(Participants) | Arm I (Fosaprepitant Dimeglumine, Olanzapine) | Arm II (Placebo, Olanzapine) | Total |
|---|---|---|---|
| Anthracycline and cyclophosphamide (AC) | 267 | 266 | 533 |
| Cisplatin-containing regimen | 79 | 78 | 157 |
| 5-HT Receptor Antagonist(Participants) | Arm I (Fosaprepitant Dimeglumine, Olanzapine) | Arm II (Placebo, Olanzapine) | Total |
|---|---|---|---|
| Ondansetron | 90 | 90 | 180 |
| Palonosetron | 256 | 254 | 510 |
Showing the first 100 of 566 sites across 2 countries. Choose a country and city above to see the rest.
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: Yes — Individual Participant Data Set
Data sharing details ↗ · nctn-data-archive.nci.nih.gov
Ran from Nov 2018 to primary completion in Nov 2021, 35 months.
Results were first posted in May 2023, 1 year 6 months after primary completion.
Of 83 non-industry phase 3 interventional studies under Neoplasms, half reached primary completion within 60 months of starting (the median), counting those still running; a quarter within 43 and three quarters within 96. This study's 35 months is below that.
Counting every sponsor, half of 202 studies reached it within 50 months; a quarter within 33 and three quarters within 84.
Neoplasms covers many different conditions, not one, so the studies compared here vary widely. Read these figures as a rough guide.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Mar 2025. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Fosaprepitant
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