ClinicalTrials.gg
Sign In
CompletedNCT01499849Updated May 19, 2016Results posted

Ph3 Safety/Efficacy Study of Rolapitant for the Prevention of CINV in Subjects Receiving Highly Emetogenic Chemotherapy

A Phase 3 interventional study of Rolapitant and Granisetron in Chemotherapy-induced Nausea and Vomiting, sponsored by Tesaro, Inc.. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2016-05-19.

Sponsored by Tesaro, Inc. (part of GlaxoSmithKline) · Phase 3, Interventional, and Prevention

Phase
Phase 3
Study type
Interventional
Enrollment
532
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

This is a Phase 3, multicenter, randomized, parallel-group, double-blind, active-controlled study of rolapitant in subjects receiving HEC. Rolapitant or placebo will be administered prior to initiation of chemotherapy on Day 1 with granisetron and dexamethasone. Subjects will record all events of emesis and 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 HEC administration through Day 6 of 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 examinations, 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.

Read the detailed description

This is a Phase 3, multicenter, randomized, parallel-group, double-blind, active-controlled study of rolapitant in subjects receiving HEC (≥60 mg/m2 of cisplatin-based chemotherapy). Study drug will be administered 1 - 2 hours prior to initiation of chemotherapy on Day 1. Granisetron and dexamethasone will be administered approximately 30 minutes before initiation of chemotherapy on Day 1,except in patients receiving taxanes as part of cisplatin-based chemotherapy. Subjects will record all events of emesis and 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 NV Subject Diary prior to HEC administration through Day 6 in Cycle 1. Dexamethasone 8 mg twice daily (part of study regimen) on Days 2 through 4 is NOT considered rescue therapy. 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 AEs, physical examinations including complete neurological assessment, vital signs,electrocardiograms (ECGs), and safety laboratory values including BUN andcreatinine. All subjects are expected to complete Cycle 1 and will have the option of participating in up to five additional cycles. The study will investigate the efficacy of rolapitant for the treatment of CINV during an initial chemotherapy cycle (Cycle 1).

Safety analyses will include data from Cycle 1 and from subsequent cycles. At the Screening Visit, blood samples may be collected and stored in this study and maybe analyzed for future biomarker research related to safety and efficacy. Analysis of these samples may include DNA, RNA, or protein markers. The biomarker blood samples will be stored for up to 2 years post study completion. In addition, PK samples will be collected from subjects enrolled in selected sites.

02

Conditions studied

  • Chemotherapy-induced Nausea and Vomiting

Browse trials for

Keywords

  • Rolapitant
  • Nausea
  • Vomiting
  • CINV
  • Chemotherapy
03

In context

Vomiting

1,123 studies on the registry are indexed under Vomiting; 137 are open to participants now.

This study's enrollment of 532 is above the median of 105 across 954 interventional studies indexed under Vomiting.

Browse Vomiting studies →

Lead sponsor

Tesaro, Inc. is the lead sponsor of 33 studies on the registry; none are open to participants now.

Of its 12 completed or terminated interventional studies of FDA-regulated products, 12 (100%) have results posted.

First submitted before Tesaro, Inc. became part of GlaxoSmithKline.

Browse Tesaro, Inc. studies →All GlaxoSmithKline studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  • 18 years of age or older, of either gender, and of any race
  • has never been treated with cisplatin and is to receive the first course of cisplatin-based chemotherapy (≥60 mg/m2)
  • Karnofsky performance score of ≥60
  • Predicted life expectancy of ≥4 months
  • Adequate bone marrow, kidney, and liver function

Exclusion criteria

Exclusion Criteria:

  • Contraindication to cisplatin, granisetron, or dexamethasone
  • Is pregnant or breast feeding
  • Has previously received cisplatin or subject is planning to receive multiple days of cisplatin in a single cycle
  • 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 4 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, pemetrexed)
  • 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 cisplatin-based chemotherapy on Day 1 in Cycle 1.
05

Study design

Phase
Phase 3
Primary purpose
Prevention
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Participant, Investigator)
Enrollment
532 participants (actual)

Study arms

  • Experimental
    Rolapitant

    Day 1: Rolapitant (200 mg PO) + Granisetron (10 mcg/kg IV) + dexamethasone (20 mg PO) Days 2-4: Dexamethasone (8 mg PO) will be administered orally BID.

    Drug: Rolapitant · Drug: Granisetron · Drug: dexamethasone

  • Placebo comparator
    Placebo + Granisetron + Dexamethasone

    Day 1: Placebo + Granisetron (10 mcg/kg IV)+ dexamethasone (20 mg PO) Days 2-4: Dexamethasone (8 mg PO) will be administered orally BID.

    Drug: Granisetron · Drug: dexamethasone · Drug: Placebo

Interventions

  • DrugRolapitant

    (4 X 50 mg capsules) 200 mg PO

    Also known as: Varubi

  • DrugGranisetron

    10 mcg/kg IV

    Also known as: Kytril, Granisol

  • Drugdexamethasone

    20 mg PO and 8 mg PO

    Also known as: Decadron

  • DrugPlacebo

    (4 X 0 mg capsules) 0 mg PO

    Also known as: Placebo to match Rolapitant

06

What researchers measure

Primary outcomes

  1. 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 HEC. The primary outcome will be based on complete response (defined as no emetic episodes and no rescue medication) in the delayed phase (\>24 to 120 hours).

    Time frame: >24 to 120 hours post chemotherapy

Secondary outcomes

  1. 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

  2. Overall Response Rate

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

    Time frame: 0 to 120 hours

07

Results

Posted Nov 4, 2015

Participant flow

Participant flow — Overall Study
MilestoneRolapitant + Granisetron + DexamethasonePlacebo + Granisetron + Dexamethasone
Started266266
Completed4240
Not completed224226
Withdrew: Adverse event2832
Withdrew: Chemo completed or change in therapy7067
Withdrew: Withdrawal by subject4343
Withdrew: Death57
Withdrew: Disease progression1110
Withdrew: Protocol violation1111
Withdrew: Physician decision2019
Withdrew: Lack of efficacy34
Withdrew: Lost to follow-up63
Withdrew: Other reasons2730

Outcome measures

PrimaryNo 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 HEC. The primary outcome will be based on complete response (defined as no emetic episodes and no rescue medication) in the delayed phase (\>24 to 120 hours).

Time frame:
>24 to 120 hours post chemotherapy
Reported as:
Number · percentage of participants
No Emetic Episodes and No Rescue Medication
percentage of participantsRolapitant + Granisetron + DexamethasonePlacebo + Granisetron + Dexamethasone
No Emetic Episodes and No Rescue Medication72.7 (66.9 to 78.0)58.4 (52.2 to 64.4)
Statistical analysis
  • Rolapitant + Granisetron + Dexamethasone vs Placebo + Granisetron + Dexamethasone · Cochran-Mantel-Haenszel · p = <0.001 (To control for multiplicity, analyses were performed hierarchically. For the CR delayed the threshold for statistical significance was 0.05; no further adjustment for multiplicity were required for the primary endpoint.) · Odds ratio (or): 1.9 · 95% CI 1.3 to 2.7Cochran Mantel Haenszel (CMH) test was stratified by sex. Missing data were imputed as treatment failures.
SecondaryAcute 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
Reported as:
Number · percentage of participants
Acute Phase Response
percentage of participantsRolapitant + Granisetron + DexamethasonePlacebo + Granisetron + Dexamethasone
Acute Phase Response83.7 (78.7 to 88.0)73.7 (67.9 to 78.9)
Statistical analysis
  • Rolapitant + Granisetron + Dexamethasone vs Placebo + Granisetron + Dexamethasone · Cochran-Mantel-Haenszel · p = 0.005 (To control for multiplicity, analyses were performed hierarchically. CR-acute was tested only if the result for the primary endpoint, CR delayed, was statistically significant.) · Odds ratio (or): 1.8 · 95% CI 1.2 to 2.8Cochran Mantel Haenszel (CMH) test was stratified by sex. Missing data were imputed as treatment failures.
SecondaryOverall Response Rate

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

Time frame:
0 to 120 hours
Reported as:
Number · percentage of participants
Overall Response Rate
percentage of participantsRolapitant + Granisetron + DexamethasonePlacebo + Granisetron + Dexamethasone
Overall Response Rate70.1 (64.2 to 75.5)56.5 (50.2 to 62.6)
Statistical analysis
  • Rolapitant + Granisetron + Dexamethasone vs Placebo + Granisetron + Dexamethasone · Cochran-Mantel-Haenszel · p = 0.001 (To control for multiplicity, analyses were performed hierarchically. CR overall was tested only if both CR delayed and CR acute were statistically significant.) · Odds ratio (or): 1.8 · 95% CI 1.3 to 2.6Cochran Mantel Haenszel (CMH) test was stratified by sex. Missing data were imputed as treatment failures.

Adverse events

Collected over Up to 6 cycles of treatment (median number cycles=2; median duration of each cycle = 21-22 days). Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Rolapitant + Granisetron + Dexamethasone—37/263 (14.1%)187/263 (71.1%)
Placebo + Granisetron + Dexamethasone—54/263 (20.5%)198/263 (75.3%)
Most frequent serious events
Showing 10 of 72
Most frequent serious events
EventRolapitant + Granisetron + DexamethasonePlacebo + Granisetron + Dexamethasone
VomitingGastrointestinal disorders0/2635/263
PneumoniaInfections and infestations5/2631/263
DehydrationMetabolism and nutrition disorders2/2635/263
Pulmonary EmbolismRespiratory, thoracic and mediastinal disorders2/2634/263
Febrile NeutropeniaBlood and lymphatic system disorders3/2632/263
DeathGeneral disorders0/2633/263
Renal Failure AcuteRenal and urinary disorders2/2633/263
NeutropeniaBlood and lymphatic system disorders0/2632/263
NauseaGastrointestinal disorders0/2632/263
Disease ProgressionGeneral disorders1/2632/263
Most frequent other events
Showing 10 of 17
Most frequent other events
EventRolapitant + Granisetron + DexamethasonePlacebo + Granisetron + Dexamethasone
AstheniaGeneral disorders35/26340/263
FatigueGeneral disorders36/26330/263
Decreased AppetiteMetabolism and nutrition disorders30/26336/263
NauseaGastrointestinal disorders24/26335/263
NeutropeniaBlood and lymphatic system disorders33/26323/263
AnaemiaBlood and lymphatic system disorders28/26332/263
ConstipationGastrointestinal disorders26/26329/263
AlopeciaSkin and subcutaneous tissue disorders22/26323/263
vomitingGastrointestinal disorders9/26322/263
DiarrhoeaGastrointestinal disorders20/26318/263

Baseline characteristics

Overall Number of Baseline Participants only included the Modified Intent to Treat (MITT) population: * 266 subjects were randomized to Rolapitant and 266 were randomized to control; * 264 of those randomized to Rolapitant received study drug in Cycle 1; 262 of those who were randomized to control received study drug in Cycle 1.

Age, Continuous
Age, Continuous(years)Rolapitant + Granisetron + DexamethasonePlacebo + Granisetron + DexamethasoneTotal
Mean57.0 ± 10.0857.7 ± 11.1557.3 ± 10.62
Sex: Female, Male
Sex: Female, Male(Participants)Rolapitant + Granisetron + DexamethasonePlacebo + Granisetron + DexamethasoneTotal
Female110112222
Male154150304
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Rolapitant + Granisetron + DexamethasonePlacebo + Granisetron + DexamethasoneTotal
Hispanic or Latino333467
Not Hispanic or Latino231228459
Unknown or Not Reported000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Rolapitant + Granisetron + DexamethasonePlacebo + Granisetron + DexamethasoneTotal
American Indian or Alaska Native202
Asian6156117
Native Hawaiian or Other Pacific Islander000
Black or African American235
White178179357
More than one race000
Unknown or Not Reported212445
08

Study locations

1 site
  • TESARO Inc
    Waltham, Massachusetts 02451, United States
09

References and documents

Publications

  • Rapoport BL, Chasen MR, Gridelli C, Urban L, Modiano MR, Schnadig ID, Poma A, Arora S, Kansra V, Schwartzberg LS, Navari RM. Safety and efficacy of rolapitant for prevention of chemotherapy-induced nausea and vomiting after administration of cisplatin-based highly emetogenic chemotherapy in patients with cancer: two randomised, active-controlled, double-blind, phase 3 trials. Lancet Oncol. 2015 Sep;16(9):1079-1089. doi: 10.1016/S1470-2045(15)00035-2. Epub 2015 Aug 10. PubMed 26272769 ↗
10

Timeline

Tracking since Sep 25, 2026
Not marked actual or estimatedDates not marked actual or estimated

The record gives a start of Feb 2012, a primary completion of May 2014 and a completion of May 2014. It does not say whether these dates are actual or estimated.

Results were first posted in Nov 2015, 1 year 6 months after primary completion.

How these figures are worked out, and which studies are left out of them.

Registered
Dec 20, 2011
First posted
Dec 26, 2011
Start
Feb 2012
Primary completionActual
May 2014
CompletionActual
May 2014
Results first posted
Nov 4, 2015
Last update
May 19, 2016
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on May 19, 2016, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT01499849
Lead sponsor
Tesaro, Inc.
Responsible party
Sponsor
First posted
Dec 26, 2011
Start date
Feb 2012
Primary completion
May 2014
Completion
May 2014
Results posted
Nov 4, 2015
Last update
May 19, 2016

Study contacts

Dennis Vargo, MD
study director · Tesaro, Inc.

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Oct 2012. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Studies of the drug tested here: Rolapitant

Other studies in this condition

Vomiting →

Other studies from this sponsor

Tesaro, Inc. →

Start the discussion