Trial Outcomes & Findings for Efficacy Study of Olaparib With Paclitaxel Versus Paclitaxel in Gastric Cancer Patients (NCT NCT01063517)

Last Updated: 2023-07-20

Results Overview

PFS is defined as the time from randomisation till objective progression or death. In absence of progression or death, the time is calculated from randomisation till last evaluable scanning visit.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

124 participants

Primary outcome timeframe

Tumour assessments were carried out at baseline and then follow up assessments taken every 8 weeks up to Week 40 and then every 16 weeks until objective disease progression as defined by RECIST 1.1, assessed maximum up to 27 months

Results posted on

2023-07-20

Participant Flow

This study was conducted at 13 sites in South Korea. Enrolment started in February 2010 and was completed in May 2012. In total 124 patients were randomised in the study (62 in the olaparib+paclitaxel arm and 62 in the placebo+paclitaxel arm).

Patients of either sex, age more than 17 years with recurrent or metastatic gastric cancer that had progressed following first line therapy, a confirmed Ataxia Telangiectasia Mutation (ATM) status, Eastern Co operative Oncology Group (ECOG) performance status ≤2, normal organ and bone marrow function, and life expectancy ≥16 weeks.

Participant milestones

Participant milestones
Measure	Olaparib+Paclitaxel Olaparib 100 mg twice daily in tablet formulation in combination with paclitaxel 80 mg/m2 intravenous on Days 1, 8, and 15 of a 4 week schedule. It was expected that patients would receive between 6 to 10 cycles of paclitaxel after which olaparib dose was increased to 200 mg bd as monotherapy.	Placebo+Paclitaxel Matching placebo 100 mg twice daily in tablet formulation in combination with paclitaxel 80 mg/m2 intravenous on Days 1, 8, and 15 of a 4 week schedule. It was expected that patients would receive between 6 to 10 cycles of paclitaxel after which placebo dose was increased to 200 mg bd as monotherapy.
Overall Study STARTED	62	62
Overall Study Received Randomised Treatment	61	62
Overall Study COMPLETED	4	2
Overall Study NOT COMPLETED	58	60

Reasons for withdrawal

Reasons for withdrawal
Measure	Olaparib+Paclitaxel Olaparib 100 mg twice daily in tablet formulation in combination with paclitaxel 80 mg/m2 intravenous on Days 1, 8, and 15 of a 4 week schedule. It was expected that patients would receive between 6 to 10 cycles of paclitaxel after which olaparib dose was increased to 200 mg bd as monotherapy.	Placebo+Paclitaxel Matching placebo 100 mg twice daily in tablet formulation in combination with paclitaxel 80 mg/m2 intravenous on Days 1, 8, and 15 of a 4 week schedule. It was expected that patients would receive between 6 to 10 cycles of paclitaxel after which placebo dose was increased to 200 mg bd as monotherapy.
Overall Study Consent withdrawal	1	0
Overall Study Study reached data cut-off	19	7
Overall Study Lost to Follow-up	4	3
Overall Study Withdrawal by Subject	1	2
Overall Study Death	33	48

Baseline Characteristics

Efficacy Study of Olaparib With Paclitaxel Versus Paclitaxel in Gastric Cancer Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Olaparib+Paclitaxel n=62 Participants Olaparib 100 mg twice daily in tablet formulation in combination with paclitaxel 80 mg/m2 intravenous on Days 1, 8, and 15 of a 4 week schedule. It was expected that patients would receive between 6 to 10 cycles of paclitaxel after which olaparib dose was increased to 200 mg bd as monotherapy.	Placebo+Paclitaxel n=62 Participants Matching placebo 100 mg twice daily in tablet formulation in combination with paclitaxel 80 mg/m2 intravenous on Days 1, 8, and 15 of a 4 week schedule. It was expected that patients would receive between 6 to 10 cycles of paclitaxel after which placebo dose was increased to 200 mg bd as monotherapy.	Total n=124 Participants Total of all reporting groups
Age, Continuous	59.0 years STANDARD_DEVIATION 11.61 • n=99 Participants	59.4 years STANDARD_DEVIATION 11.98 • n=107 Participants	59.2 years STANDARD_DEVIATION 11.75 • n=206 Participants
Age, Customized < 50 years	13 Participants n=99 Participants	10 Participants n=107 Participants	23 Participants n=206 Participants
Age, Customized >=50 to <65 years	22 Participants n=99 Participants	30 Participants n=107 Participants	52 Participants n=206 Participants
Age, Customized >= 65 years	27 Participants n=99 Participants	22 Participants n=107 Participants	49 Participants n=206 Participants
Sex: Female, Male Female	13 Participants n=99 Participants	18 Participants n=107 Participants	31 Participants n=206 Participants
Sex: Female, Male Male	49 Participants n=99 Participants	44 Participants n=107 Participants	93 Participants n=206 Participants
Race/Ethnicity, Customized Asian	62 Participants n=99 Participants	62 Participants n=107 Participants	124 Participants n=206 Participants
Race/Ethnicity, Customized Other	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
ATM status Negative	31 Participants n=99 Participants	32 Participants n=107 Participants	63 Participants n=206 Participants
ATM status Positive	31 Participants n=99 Participants	30 Participants n=107 Participants	61 Participants n=206 Participants

PRIMARY outcome

Timeframe: Tumour assessments were carried out at baseline and then follow up assessments taken every 8 weeks up to Week 40 and then every 16 weeks until objective disease progression as defined by RECIST 1.1, assessed maximum up to 27 months

Population: Full analysis set including all randomised patients

PFS is defined as the time from randomisation till objective progression or death. In absence of progression or death, the time is calculated from randomisation till last evaluable scanning visit.

Outcome measures

Outcome measures
Measure	Placebo+Paclitaxel n=62 Participants Matching placebo 100 mg twice daily in tablet formulation in combination with paclitaxel 80 mg/m2 intravenous on Days 1, 8, and 15 of a 4 week schedule. It was expected that patients would receive between 6 to 10 cycles of paclitaxel after which placebo dose was increased to 200 mg bd as monotherapy.	Olaparib+Paclitaxel n=62 Participants Olaparib 100 mg twice daily in tablet formulation in combination with paclitaxel 80 mg/m2 intravenous on Days 1, 8, and 15 of a 4 week schedule. It was expected that patients would receive between 6 to 10 cycles of paclitaxel after which olaparib dose was increased to 200 mg bd as monotherapy.
Progression Free Survival (PFS) in the Overall Study Population	3.55 months Interval 1.74 to 5.82	3.91 months Interval 3.02 to 7.13

PRIMARY outcome

Timeframe: Tumour assessments are carried out at baseline and then follow up assessments taken every 8 weeks up to Week 40 and then every 16 weeks until objective disease progression as defined by RECIST 1.1, assessed maximum up to 27 months

Population: Full analysis set including randomised ATM negative patients

PFS is defined as the time from randomisation till objective progression or death. In absence of progression or death, the time is calculated from randomisation till last evaluable scanning visit.

Outcome measures

Outcome measures
Measure	Placebo+Paclitaxel n=32 Participants Matching placebo 100 mg twice daily in tablet formulation in combination with paclitaxel 80 mg/m2 intravenous on Days 1, 8, and 15 of a 4 week schedule. It was expected that patients would receive between 6 to 10 cycles of paclitaxel after which placebo dose was increased to 200 mg bd as monotherapy.	Olaparib+Paclitaxel n=31 Participants Olaparib 100 mg twice daily in tablet formulation in combination with paclitaxel 80 mg/m2 intravenous on Days 1, 8, and 15 of a 4 week schedule. It was expected that patients would receive between 6 to 10 cycles of paclitaxel after which olaparib dose was increased to 200 mg bd as monotherapy.
Progression Free Survival (PFS) in Patients With Tumours Defined as Homologous Recombination Deficient by Loss of Ataxia-Telangiectasia Mutation (ATM) Protein [ATM Negative Patients]	3.68 months Interval 1.77 to 5.82	5.29 months Interval 3.38 to 5.72

SECONDARY outcome

Timeframe: Survival follow up from randomisation till death of the patient or till end of study in absence of death, assessed maximum up to 27 months

Population: Full analysis set including all randomised patients

Overall survival is defined as the duration from randomisation till death. In absence of death, the time is calculated from randomisation till the date subject last known to be alive.

Outcome measures

Outcome measures
Measure	Placebo+Paclitaxel n=62 Participants Matching placebo 100 mg twice daily in tablet formulation in combination with paclitaxel 80 mg/m2 intravenous on Days 1, 8, and 15 of a 4 week schedule. It was expected that patients would receive between 6 to 10 cycles of paclitaxel after which placebo dose was increased to 200 mg bd as monotherapy.	Olaparib+Paclitaxel n=62 Participants Olaparib 100 mg twice daily in tablet formulation in combination with paclitaxel 80 mg/m2 intravenous on Days 1, 8, and 15 of a 4 week schedule. It was expected that patients would receive between 6 to 10 cycles of paclitaxel after which olaparib dose was increased to 200 mg bd as monotherapy.
Overall Survival (OS) in the Overall Study Population	8.3 months Interval 5.3 to 14.9	13.1 months Interval 7.1 to NA: There were insufficient events to calculate.

SECONDARY outcome

Timeframe: Survival follow up from randomisation till death of the patient or till end of study in absence of death, assessed maximum up to 27 months

Population: Full analysis set including randomised ATM negative patients

Overall survival is defined as the duration from randomisation till death. In absence of death, the time is calculated from randomisation till the date subject last known to be alive.

Outcome measures

Outcome measures
Measure	Placebo+Paclitaxel n=32 Participants Matching placebo 100 mg twice daily in tablet formulation in combination with paclitaxel 80 mg/m2 intravenous on Days 1, 8, and 15 of a 4 week schedule. It was expected that patients would receive between 6 to 10 cycles of paclitaxel after which placebo dose was increased to 200 mg bd as monotherapy.	Olaparib+Paclitaxel n=31 Participants Olaparib 100 mg twice daily in tablet formulation in combination with paclitaxel 80 mg/m2 intravenous on Days 1, 8, and 15 of a 4 week schedule. It was expected that patients would receive between 6 to 10 cycles of paclitaxel after which olaparib dose was increased to 200 mg bd as monotherapy.
Overall Survival (OS) in ATM Negative Patients	8.20 months Interval 5.1 to 13.1	NA months Interval 9.3 to More than 50% of patients were alive at the data cut-off date

SECONDARY outcome

Timeframe: Tumour assessments carried out at baseline, 28 days before randomisation then every 8 weeks until week 40, after week 40 assessments will be carried out every 16 weeks until objective disease progression, assessed maximum up to 27 months

Population: Evaluable for response population - randomised patients having measurable disease at baseline.

Objective response rate is the proportion of patients with at least one measurable lesion at baseline, who experienced complete or partial response at least once during the assessment period, according to the definitions of Response Evaluation Criteria In Solid Tumours (RECIST version 1.1).

Outcome measures

Outcome measures
Measure	Placebo+Paclitaxel n=47 Participants Matching placebo 100 mg twice daily in tablet formulation in combination with paclitaxel 80 mg/m2 intravenous on Days 1, 8, and 15 of a 4 week schedule. It was expected that patients would receive between 6 to 10 cycles of paclitaxel after which placebo dose was increased to 200 mg bd as monotherapy.	Olaparib+Paclitaxel n=53 Participants Olaparib 100 mg twice daily in tablet formulation in combination with paclitaxel 80 mg/m2 intravenous on Days 1, 8, and 15 of a 4 week schedule. It was expected that patients would receive between 6 to 10 cycles of paclitaxel after which olaparib dose was increased to 200 mg bd as monotherapy.
Objective Response Rate (ORR) in the Overall Study Population	9 Participants	14 Participants

SECONDARY outcome

Population: Evaluable for response population ATM negative patients - randomised ATM negative patients having measurable disease at baseline.

Objective response rate is the proportion of ATM negative patients with at least one measurable lesion at baseline, who experienced complete or partial response at least once during the assessment period, according to the definitions of Response Evaluation Criteria In Solid Tumours (RECIST version 1.1).

Outcome measures

Outcome measures
Measure	Placebo+Paclitaxel n=23 Participants Matching placebo 100 mg twice daily in tablet formulation in combination with paclitaxel 80 mg/m2 intravenous on Days 1, 8, and 15 of a 4 week schedule. It was expected that patients would receive between 6 to 10 cycles of paclitaxel after which placebo dose was increased to 200 mg bd as monotherapy.	Olaparib+Paclitaxel n=26 Participants Olaparib 100 mg twice daily in tablet formulation in combination with paclitaxel 80 mg/m2 intravenous on Days 1, 8, and 15 of a 4 week schedule. It was expected that patients would receive between 6 to 10 cycles of paclitaxel after which olaparib dose was increased to 200 mg bd as monotherapy.
Objective Response Rate (ORR) in the ATM Negative Patients	6 Participants	9 Participants

SECONDARY outcome

Timeframe: Tumour scans done at Baseline and week 8

Population: Evaluable for response population - randomised patients having measurable disease at baseline.

Percentage change in tumour size from baseline to Week 8 calculated as 100 X (week 8 tumour size - baseline tumour size) / (baseline tumour size)

Outcome measures

Outcome measures
Measure	Placebo+Paclitaxel n=47 Participants Matching placebo 100 mg twice daily in tablet formulation in combination with paclitaxel 80 mg/m2 intravenous on Days 1, 8, and 15 of a 4 week schedule. It was expected that patients would receive between 6 to 10 cycles of paclitaxel after which placebo dose was increased to 200 mg bd as monotherapy.	Olaparib+Paclitaxel n=52 Participants Olaparib 100 mg twice daily in tablet formulation in combination with paclitaxel 80 mg/m2 intravenous on Days 1, 8, and 15 of a 4 week schedule. It was expected that patients would receive between 6 to 10 cycles of paclitaxel after which olaparib dose was increased to 200 mg bd as monotherapy.
Percentage Change in Tumour Size at Week 8 in the Overall Study Population	2.2 Percent change Standard Deviation 35.6	-5.8 Percent change Standard Deviation 29.09

SECONDARY outcome

Timeframe: Tumour scans done at Baseline and week 8

Population: Evaluable for response population ATM negative patients - randomised ATM negative patients having measurable disease at baseline.

Percentage change in tumour size from baseline to Week 8 calculated as 100 X (week 8 tumour size - baseline tumour size) / (baseline tumour size)