Trial Outcomes & Findings for Ph3 Safety/Efficacy Study of Rolapitant for the Prevention of CINV in Subjects Receiving Highly Emetogenic Chemotherapy (NCT NCT01500213)

Last Updated: 2016-03-02

Results Overview

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 emesis and no rescue medication) in the delayed phase (\>24 to 120 hours).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

555 participants

Primary outcome timeframe

>24 to 120 hours post chemotherapy

Results posted on

2016-03-02

Participant Flow

Participant milestones

Participant milestones
Measure	Rolapitant + Granisetron + Dexamethasone * Oral dose of rolapitant 180 mg (equivalent to 200 mg rolapitant hydrochloride monohydrate) 1-2 h before administration of chemotherapy * Granisetron (10 μg/kg intravenously) about 30 min before chemotherapy * Dexamethasone (20 mg orally) about 30 min before chemotherapy, and dexamethasone 8 mg orally twice daily on days 2-4	Placebo + Granisetron + Dexamethasone * Matching placebo 1-2 h before administration of chemotherapy * Granisetron (10 μg/kg intravenously) about 30 min before chemotherapy * Dexamethasone (20 mg orally) about 30 min before chemotherapy, and dexamethasone 8 mg orally twice daily on days 2-4
Overall Study STARTED	278	277
Overall Study COMPLETED	61	53
Overall Study NOT COMPLETED	217	224

Reasons for withdrawal

Reasons for withdrawal
Measure	Rolapitant + Granisetron + Dexamethasone * Oral dose of rolapitant 180 mg (equivalent to 200 mg rolapitant hydrochloride monohydrate) 1-2 h before administration of chemotherapy * Granisetron (10 μg/kg intravenously) about 30 min before chemotherapy * Dexamethasone (20 mg orally) about 30 min before chemotherapy, and dexamethasone 8 mg orally twice daily on days 2-4	Placebo + Granisetron + Dexamethasone * Matching placebo 1-2 h before administration of chemotherapy * Granisetron (10 μg/kg intravenously) about 30 min before chemotherapy * Dexamethasone (20 mg orally) about 30 min before chemotherapy, and dexamethasone 8 mg orally twice daily on days 2-4
Overall Study Adverse Event	35	35
Overall Study Chemo Completed or Change in Therapy	84	81
Overall Study Withdrawal by Subject	28	37
Overall Study Death	7	3
Overall Study Disease Progression	13	21
Overall Study Protocol Violation	19	19
Overall Study Physician Decision	12	10
Overall Study Lack of Efficacy	9	7
Overall Study Lost to Follow-up	3	6
Overall Study Other Reasons	7	5

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Rolapitant + Granisetron + Dexamethasone n=271 Participants * Oral dose of rolapitant 180 mg (equivalent to 200 mg rolapitant hydrochloride monohydrate) 1-2 h before administration of chemotherapy * Granisetron (10 μg/kg intravenously) about 30 min before chemotherapy * Dexamethasone (20 mg orally) about 30 min before chemotherapy, and dexamethasone 8 mg orally twice daily on days 2-4	Placebo + Granisetron + Dexamethasone n=273 Participants * Matching placebo 1-2 h before administration of chemotherapy * Granisetron (10 μg/kg intravenously) about 30 min before chemotherapy * Dexamethasone (20 mg orally) about 30 min before chemotherapy, and dexamethasone 8 mg orally twice daily on days 2-4	Total n=544 Participants Total of all reporting groups
Age, Continuous	58.5 years STANDARD_DEVIATION 10.05 • n=5 Participants	58.5 years STANDARD_DEVIATION 9.25 • n=7 Participants	58.5 years STANDARD_DEVIATION 9.65 • n=5 Participants
Sex: Female, Male Female	88 Participants n=5 Participants	87 Participants n=7 Participants	175 Participants n=5 Participants
Sex: Female, Male Male	183 Participants n=5 Participants	186 Participants n=7 Participants	369 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	36 Participants n=5 Participants	38 Participants n=7 Participants	74 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	235 Participants n=5 Participants	235 Participants n=7 Participants	470 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=5 Participants	8 Participants n=7 Participants	10 Participants n=5 Participants
Race (NIH/OMB) Asian	34 Participants n=5 Participants	41 Participants n=7 Participants	75 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) White	226 Participants n=5 Participants	212 Participants n=7 Participants	438 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	7 Participants n=5 Participants	9 Participants n=7 Participants	16 Participants n=5 Participants

PRIMARY outcome

Timeframe: >24 to 120 hours post chemotherapy

Population: MITT

Outcome measures

Outcome measures
Measure	Rolapitant + Granisetron + Dexamethasone n=271 Participants * Oral dose of rolapitant 180 mg (equivalent to 200 mg rolapitant hydrochloride monohydrate) 1-2 h before administration of chemotherapy * Granisetron (10 μg/kg intravenously) about 30 min before chemotherapy * Dexamethasone (20 mg orally) about 30 min before chemotherapy, and dexamethasone 8 mg orally twice daily on days 2-4	Placebo + Granisetron + Dexamethasone n=273 Participants * Matching placebo 1-2 h before administration of chemotherapy * Granisetron (10 μg/kg intravenously) about 30 min before chemotherapy * Dexamethasone (20 mg orally) about 30 min before chemotherapy, and dexamethasone 8 mg orally twice daily on days 2-4
No Emetic Episodes and No Rescue Medication	70.1 percentage of participants Interval 64.3 to 75.5	61.9 percentage of participants Interval 55.9 to 67.7

SECONDARY outcome

Timeframe: 0 to 24 hours

Population: MITT

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

Outcome measures

Outcome measures
Measure	Rolapitant + Granisetron + Dexamethasone n=271 Participants * Oral dose of rolapitant 180 mg (equivalent to 200 mg rolapitant hydrochloride monohydrate) 1-2 h before administration of chemotherapy * Granisetron (10 μg/kg intravenously) about 30 min before chemotherapy * Dexamethasone (20 mg orally) about 30 min before chemotherapy, and dexamethasone 8 mg orally twice daily on days 2-4	Placebo + Granisetron + Dexamethasone n=273 Participants * Matching placebo 1-2 h before administration of chemotherapy * Granisetron (10 μg/kg intravenously) about 30 min before chemotherapy * Dexamethasone (20 mg orally) about 30 min before chemotherapy, and dexamethasone 8 mg orally twice daily on days 2-4
Acute Phase Response	83.4 percentage of participants Interval 78.4 to 87.6	79.5 percentage of participants Interval 74.2 to 84.1

SECONDARY outcome

Timeframe: 0 to 120 hours

Population: MITT

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

Outcome measures

Outcome measures
Measure	Rolapitant + Granisetron + Dexamethasone n=271 Participants * Oral dose of rolapitant 180 mg (equivalent to 200 mg rolapitant hydrochloride monohydrate) 1-2 h before administration of chemotherapy * Granisetron (10 μg/kg intravenously) about 30 min before chemotherapy * Dexamethasone (20 mg orally) about 30 min before chemotherapy, and dexamethasone 8 mg orally twice daily on days 2-4	Placebo + Granisetron + Dexamethasone n=273 Participants * Matching placebo 1-2 h before administration of chemotherapy * Granisetron (10 μg/kg intravenously) about 30 min before chemotherapy * Dexamethasone (20 mg orally) about 30 min before chemotherapy, and dexamethasone 8 mg orally twice daily on days 2-4
Overall Response Rate	67.5 percentage of participants Interval 61.6 to 73.1	60.4 percentage of participants Interval 54.4 to 66.3

Adverse Events

Rolapitant + Granisetron + Dexamethasone

Serious events: 80 serious events

Other events: 225 other events

Deaths: 0 deaths

Placebo + Granisetron + Dexamethasone

Serious events: 65 serious events

Other events: 211 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Martin Huber, M.D., Senior Vice President and Chief Medical Officer

Tesaro

Phone: 862.228.2483

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Rolapitant + Granisetron + Dexamethasone n=272 participants at risk * Oral dose of rolapitant 180 mg (equivalent to 200 mg rolapitant hydrochloride monohydrate) 1-2 h before administration of chemotherapy * Granisetron (10 μg/kg intravenously) about 30 min before chemotherapy * Dexamethasone (20 mg orally) about 30 min before chemotherapy, and dexamethasone 8 mg orally twice daily on days 2-4 * 278 subjects were randomized to Rolapitant * 272 of those randomized to Rolapitant received Rolapitant in C1 * Safety = 272 Rolapitant	Placebo + Granisetron + Dexamethasone n=274 participants at risk * Matching placebo 1-2 h before administration of chemotherapy * Granisetron (10 μg/kg intravenously) about 30 min before chemotherapy * Dexamethasone (20 mg orally) about 30 min before chemotherapy, and dexamethasone 8 mg orally twice daily on days 2-4 * 277 subjects were randomized to control; * 274 of those who were randomized to control received control in C1. * Safety = 274 control
Blood and lymphatic system disorders Anaemia	11.0% 30/272 • Up to 6 cycles (median number of cycles=3; median duration of each cycle = 21-23 days) of treatment	5.8% 16/274 • Up to 6 cycles (median number of cycles=3; median duration of each cycle = 21-23 days) of treatment
Blood and lymphatic system disorders Neutropenia	14.3% 39/272 • Up to 6 cycles (median number of cycles=3; median duration of each cycle = 21-23 days) of treatment	11.7% 32/274 • Up to 6 cycles (median number of cycles=3; median duration of each cycle = 21-23 days) of treatment
Gastrointestinal disorders Abdominal Pain	5.1% 14/272 • Up to 6 cycles (median number of cycles=3; median duration of each cycle = 21-23 days) of treatment	3.3% 9/274 • Up to 6 cycles (median number of cycles=3; median duration of each cycle = 21-23 days) of treatment
Gastrointestinal disorders Constipation	13.6% 37/272 • Up to 6 cycles (median number of cycles=3; median duration of each cycle = 21-23 days) of treatment	14.6% 40/274 • Up to 6 cycles (median number of cycles=3; median duration of each cycle = 21-23 days) of treatment
Gastrointestinal disorders Diarrhoea	12.5% 34/272 • Up to 6 cycles (median number of cycles=3; median duration of each cycle = 21-23 days) of treatment	10.2% 28/274 • Up to 6 cycles (median number of cycles=3; median duration of each cycle = 21-23 days) of treatment
Gastrointestinal disorders Dyspepsia	3.7% 10/272 • Up to 6 cycles (median number of cycles=3; median duration of each cycle = 21-23 days) of treatment	5.1% 14/274 • Up to 6 cycles (median number of cycles=3; median duration of each cycle = 21-23 days) of treatment
Gastrointestinal disorders Nausea	11.8% 32/272 • Up to 6 cycles (median number of cycles=3; median duration of each cycle = 21-23 days) of treatment	12.8% 35/274 • Up to 6 cycles (median number of cycles=3; median duration of each cycle = 21-23 days) of treatment
Gastrointestinal disorders Vomiting	5.1% 14/272 • Up to 6 cycles (median number of cycles=3; median duration of each cycle = 21-23 days) of treatment	8.4% 23/274 • Up to 6 cycles (median number of cycles=3; median duration of each cycle = 21-23 days) of treatment
General disorders Asthenia	19.1% 52/272 • Up to 6 cycles (median number of cycles=3; median duration of each cycle = 21-23 days) of treatment	20.1% 55/274 • Up to 6 cycles (median number of cycles=3; median duration of each cycle = 21-23 days) of treatment
General disorders Fatigue	7.7% 21/272 • Up to 6 cycles (median number of cycles=3; median duration of each cycle = 21-23 days) of treatment	10.2% 28/274 • Up to 6 cycles (median number of cycles=3; median duration of each cycle = 21-23 days) of treatment
General disorders Mucosal Inflammation	7.7% 21/272 • Up to 6 cycles (median number of cycles=3; median duration of each cycle = 21-23 days) of treatment	7.7% 21/274 • Up to 6 cycles (median number of cycles=3; median duration of each cycle = 21-23 days) of treatment
Metabolism and nutrition disorders Decreased Appetite	14.3% 39/272 • Up to 6 cycles (median number of cycles=3; median duration of each cycle = 21-23 days) of treatment	12.8% 35/274 • Up to 6 cycles (median number of cycles=3; median duration of each cycle = 21-23 days) of treatment
Metabolism and nutrition disorders Hypomagnesaemia	5.9% 16/272 • Up to 6 cycles (median number of cycles=3; median duration of each cycle = 21-23 days) of treatment	5.8% 16/274 • Up to 6 cycles (median number of cycles=3; median duration of each cycle = 21-23 days) of treatment
Nervous system disorders Headache	5.5% 15/272 • Up to 6 cycles (median number of cycles=3; median duration of each cycle = 21-23 days) of treatment	4.4% 12/274 • Up to 6 cycles (median number of cycles=3; median duration of each cycle = 21-23 days) of treatment
Psychiatric disorders Insomnia	2.6% 7/272 • Up to 6 cycles (median number of cycles=3; median duration of each cycle = 21-23 days) of treatment	5.5% 15/274 • Up to 6 cycles (median number of cycles=3; median duration of each cycle = 21-23 days) of treatment
Respiratory, thoracic and mediastinal disorders Cough	4.0% 11/272 • Up to 6 cycles (median number of cycles=3; median duration of each cycle = 21-23 days) of treatment	5.1% 14/274 • Up to 6 cycles (median number of cycles=3; median duration of each cycle = 21-23 days) of treatment
Respiratory, thoracic and mediastinal disorders Hiccups	9.2% 25/272 • Up to 6 cycles (median number of cycles=3; median duration of each cycle = 21-23 days) of treatment	4.4% 12/274 • Up to 6 cycles (median number of cycles=3; median duration of each cycle = 21-23 days) of treatment
Skin and subcutaneous tissue disorders Alopecia	7.4% 20/272 • Up to 6 cycles (median number of cycles=3; median duration of each cycle = 21-23 days) of treatment	9.5% 26/274 • Up to 6 cycles (median number of cycles=3; median duration of each cycle = 21-23 days) of treatment