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Ph 3 Safety/Efficacy Study of Rolapitant for Prevention of CINV in Subjects Receiving Moderately Emetogenic Chemotherapy

Phase 3, Multicenter, Randomized, Double Blind, Active-Controlled Study of the Safety and Efficacy of Rolapitant for the Prevention of Chemotherapy-Induced Nausea and Vomiting (CINV) in Subjects Receiving Moderately Emetogenic Chemotherapy

Status
Completed
Phases
Phase 3
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT01500226
Enrollment
1369
Registered
2011-12-28
Start date
2012-02-29
Completion date
2014-02-28
Last updated
2016-03-02

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Chemotherapy-induced Nausea and Vomiting

Keywords

Rolapitant, Nausea, Vomiting, CINV, Chemotherapy

Brief summary

This is a Phase 3, multicenter, randomized, parallel-group, double-blind, active-controlled study of rolapitant in subjects receiving MEC. Rolapitant or placebo will be administered prior to the initiation of chemotherapy on Day 1 with granisetron and dexamethasone. Subjects will record all events of emesis and the use of rescue medication for established nausea and/or vomiting, and will indicate the severity of nausea they experienced in each of the previous 24 hours in the Nausea and Vomiting (NV) Subject Diary prior to the MEC administration through Day 6 in Cycle 1. Health-related quality of life will be measured by the FLIE Questionnaire on Day 6 of Cycle 1. Safety and tolerability will be assessed by clinical review of adverse events (AEs), physical examination, electrocardiograms (ECGs), and safety laboratory values. All subjects are expected to complete Cycle 1 and will have the option of participating in up to five additional cycles.

Detailed description

This is a Phase 3, multicenter, randomized, parallel-group, double-blind, active-controlled study of rolapitant in subjects receiving MEC. Rolapitant or placebo will be administered orally 1-2 hours prior to the initiation of chemotherapy on Day 1. Granisetron (2 mg PO) and dexamethasone (20 mg PO) will be administered approximately 30 minutes before initiation of chemotherapy. Subjects will continue to receive granisetron (2 mg daily) on Days 2 and 3. Subjects will record all events of emesis and the use of rescue medication for established nausea and/or vomiting, and will indicate the severity of nausea they experienced in each of the previous 24 hours in the Nausea and Vomiting (NV) Subject Diary prior to the MEC administration through Day 6 in Cycle 1. Health-related quality of life will be measured by the FLIE Questionnaire on Day 6 of Cycle 1. Safety and tolerability will be assessed by clinical review of adverse events (AEs), physical and neurological examinations, vital signs, electrocardiograms (ECGs), and safety laboratory values including BUN and creatinine. All subjects are expected to complete Cycle 1 and will have the option of participating in up to five additional cycles. Blood samples may be collected and stored in this study and may be analyzed for future biomarker research related to safety and efficacy.

Interventions

DRUGRolapitant

(4 X 50 mg capsule) 200 mg PO

DRUGGranisetron

2 mg PO

DRUGDexamethasone

20 mg PO

DRUGPlacebo

(4 X 0 mg capsules) 0 mg PO

Sponsors

Tesaro, Inc.
Lead SponsorINDUSTRY

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No

Inclusion criteria

* 18 years of age or older, of either gender, and of any race * Naïve to moderately or highly emetogenic chemotherapy, and is to receive a first course of MEC including one or more of the following agents: cyclophosphamide IV (\<1500 mg/m2), doxorubicin, epirubicin, carboplatin, idarubicin, ifosfamide, irinotecan, daunorubicin, cytarabine IV (\>1 g/m2). * Karnofsky performance score of ≥60 * Predicted life expectancy of ≥4 months * Adequate bone marrow, kidney, and liver function

Exclusion criteria

* Contraindication to the administration of prescribed MEC agent,granisetron, or dexamethasone * Is pregnant or breast feeding * Has taken the following agents within the last 48 hours 5-HT3 antagonists,Phenothiazines,Benzamides,Domperidone,Cannabinoids,NK1 antagonist, Benzodiazepines * Scheduled to receive any other chemotherapeutic agent with an emetogenicity level of 3 or above (Hesketh Scale) from Day -2 through Day 6, except on Day 1 * Scheduled to receive any radiation therapy to the abdomen or pelvis from Day -5 through Day 6 * Has received systemic corticosteroids or sedative antihistamines within 72 hours of Day 1 of the study except as premedication for chemotherapy (e.g., taxanes) * Symptomatic primary or metastatic CNS disease. * Has ongoing vomiting, retching, clinically significant nausea caused by any etiology, or has a history of anticipatory nausea and vomiting. * Has vomited and/or has had dry heaves/retching within 24 hours prior to the start of MECon Day 1 in Cycle 1.

Design outcomes

Primary

MeasureTime frameDescription
No Emetic Episodes and No Rescue Medication>24 to 120 hours post chemotherapyThe primary objective of this study is to determine whether administration of rolapitant with granisetron and dexamethasone improves CINV in the delayed phase (\>24 to 120 hours) of CINV compared with administration of placebo with granisetron and dexamethasone in subjects receiving MEC. The primary outcome will be based on complete response (defined as no emesis and no rescue medication) in the delayed phase (\>24 to 120 hours).

Secondary

MeasureTime frameDescription
Acute Phase Response0 to 24 hoursTo determine the effect of rolapitant on complete response rates in the acute (0 to 24 hours) phase of CINV.
Overall Response Rate0 to 120 hoursTo determine the effect of rolapitant on complete response rate in the overall (0 to 120 hours) phase of CINV.

Countries

United States

Participant flow

Participants by arm

ArmCount
Rolapitant + Granisetron + Dexamethasone
* Oral dose of rolapitant 180 mg (equivalent to 200 mg rolapitant hydrochloride monohydrate) 1-2 h before administration of chemotherapy * Granisetron (2 mg orally) about 30 min before chemotherapy. Subsequently, granisetron 2mg was administered orally to all patients once daily on days 2-3 * Dexamethasone (20 mg orally) about 30 min before chemotherapy
666
Placebo + Granisetron + Dexamethasone
* Matching placebo 1-2 h before administration of chemotherapy * Granisetron (2 mg orally) about 30 min before chemotherapy. Subsequently, granisetron 2mg was administered orally to all patients once daily on days 2-3 * Dexamethasone (20 mg orally) about 30 min before chemotherapy
666
Total1,332

Withdrawals & dropouts

PeriodReasonFG000FG001
Overall StudyAdverse Event3138
Overall StudyChemo Completed or Change in Therapy235237
Overall StudyDeath124
Overall StudyDisease Progression1614
Overall StudyLack of Efficacy1430
Overall StudyLost to Follow-up95
Overall StudyOther Reasons1916
Overall StudyPhysician Decision1715
Overall StudyProtocol Violation5339
Overall StudyWithdrawal by Subject9396

Baseline characteristics

CharacteristicPlacebo + Granisetron + DexamethasoneTotalRolapitant + Granisetron + Dexamethasone
Age, Continuous56.6 years
STANDARD_DEVIATION 12.01
56.7 years
STANDARD_DEVIATION 11.83
56.7 years
STANDARD_DEVIATION 11.65
Ethnicity (NIH/OMB)
Hispanic or Latino
70 Participants147 Participants77 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
593 Participants1177 Participants584 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
3 Participants8 Participants5 Participants
Race (NIH/OMB)
American Indian or Alaska Native
6 Participants13 Participants7 Participants
Race (NIH/OMB)
Asian
84 Participants176 Participants92 Participants
Race (NIH/OMB)
Black or African American
29 Participants53 Participants24 Participants
Race (NIH/OMB)
More than one race
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
2 Participants3 Participants1 Participants
Race (NIH/OMB)
Unknown or Not Reported
33 Participants67 Participants34 Participants
Race (NIH/OMB)
White
512 Participants1020 Participants508 Participants
Sex: Female, Male
Female
536 Participants1067 Participants531 Participants
Sex: Female, Male
Male
130 Participants265 Participants135 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
deaths
Total, all-cause mortality
— / —— / —
other
Total, other adverse events
540 / 670542 / 674
serious
Total, serious adverse events
89 / 670103 / 674

Outcome results

Primary

No Emetic Episodes and No Rescue Medication

The primary objective of this study is to determine whether administration of rolapitant with granisetron and dexamethasone improves CINV in the delayed phase (\>24 to 120 hours) of CINV compared with administration of placebo with granisetron and dexamethasone in subjects receiving MEC. The primary outcome will be based on complete response (defined as no emesis and no rescue medication) in the delayed phase (\>24 to 120 hours).

Time frame: >24 to 120 hours post chemotherapy

Population: MITT

ArmMeasureValue (NUMBER)
Rolapitant + Granisetron + DexamethasoneNo Emetic Episodes and No Rescue Medication71.3 percentage of particpants
Placebo + Granisetron + DexamethasoneNo Emetic Episodes and No Rescue Medication61.6 percentage of particpants
p-value: <0.00195% CI: [1.2, 2]Cochran-Mantel-Haenszel
Secondary

Acute Phase Response

To determine the effect of rolapitant on complete response rates in the acute (0 to 24 hours) phase of CINV.

Time frame: 0 to 24 hours

Population: MITT

ArmMeasureValue (NUMBER)
Rolapitant + Granisetron + DexamethasoneAcute Phase Response83.5 percentage of participants
Placebo + Granisetron + DexamethasoneAcute Phase Response80.3 percentage of participants
p-value: 0.14395% CI: [0.9, 1.6]Cochran-Mantel-Haenszel
Secondary

Overall Response Rate

To determine the effect of rolapitant on complete response rate in the overall (0 to 120 hours) phase of CINV.

Time frame: 0 to 120 hours

Population: MITT

ArmMeasureValue (NUMBER)
Rolapitant + Granisetron + DexamethasoneOverall Response Rate68.6 percentage of participants
Placebo + Granisetron + DexamethasoneOverall Response Rate57.8 percentage of participants
p-value: <0.00195% CI: [1.3, 2]Cochran-Mantel-Haenszel

Source: ClinicalTrials.gov · Data processed: Mar 15, 2026