Clinical trial NCT01063517: Efficacy Study of Olaparib With Paclitaxel Versus Paclitaxel in Gastric Cancer Patients
Official title: A Randomised, Double Blinded, Multicentre Phase II Study to Assess the Efficacy of Olaparib (AZD2281, KU-0059436) in Combination With Paclitaxel Versus Paclitaxel in Patients With Recurrent or Metastatic Gastric Cancer Who Progress Following First-line Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Gastric Cancer
Keywords: Poly(ADP ribose)
polymerase (PARP)
Gastric cancer
olaparib
PARP inhibitor
ATM AZD2281
Ku0059436
Homologous Recombination deficiency (HRD)
Recurrent gastric cancer
metastatic gastric cancer
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2010-02-05
Enrollment: 124
Sex: ALL
Minimum age (years): 18
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To assess the efficacy of olaparib when given in combination with paclitaxel compared with paclitaxel alone as defined by progression-free survival (PFS), in all patients with recurrent and metastatic gastric cancer who progress following first-line therapy.


Eligibility criteria: Inclusion Criteria:

* Recurrent or metastatic gastric cancer that has progressed following first line-therapy
* Confirmed ATM protein status by IHC archival tumour sample
* At least one lesion (measurable and/or non-measurable) that can be accurately assessed by imaging (CT/MRI) at baseline and follow up visits

Exclusion Criteria:

* More than one prior chemotherapy regimen for the treatment of gastric cancer in the metastatic or recurrent setting
* Any previous treatment with a PARP inhibitor, including olaparib
* Patients with second primary cancer, except; adequately treated non melanoma skin cancer, curatively treated in situ cancer of the cervix, or other solid tumours curatively treated with no evidence of disease for \>5 years

Primary outcomes:
measure: Progression Free Survival (PFS) in the Overall Study Population
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
measure: Progression Free Survival (PFS) in Patients With Tumours Defined as Homologous Recombination Deficient by Loss of Ataxia-Telangiectasia Mutation (ATM) Protein [ATM Negative Patients]
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
Secondary outcomes:
measure: Overall Survival (OS) in the Overall Study Population
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
measure: Overall Survival (OS) in ATM Negative Patients
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
measure: Objective Response Rate (ORR) in the Overall Study Population
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
measure: Objective Response Rate (ORR) in the ATM Negative Patients
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
measure: Percentage Change in Tumour Size at Week 8 in the Overall Study Population
timeFrame: Tumour scans done at Baseline and week 8
measure: Percentage Change in Tumour Size at Week 8 in the ATM Negative Patients
timeFrame: Tumour scans done at Baseline and week 8
measure: Time to Deterioration in Global Quality of Life (QoL) Score in the Overall Study Population
timeFrame: Questionnaire data collected at Baseline ie on or before date of randomisation, every 4 weeks post baseline, assessed maximum up to 27 months
measure: Time to Deterioration in QoL Fatigue Score in the Overall Study Population
timeFrame: Questionnaire data collected at Baseline ie on or before date of randomisation, every 4 weeks post baseline, assessed maximum up to 27 months
measure: Time to Deterioration in QoL Nausea & Vomiting Domain Score in the Overall Study Population
timeFrame: Questionnaire data collected at Baseline ie on or before date of randomisation, every 4 weeks post baseline, assessed maximum up to 27 months
measure: Time to Deterioration in QoL Pain Domain Score in the Overall Study Population
timeFrame: Questionnaire data collected at Baseline ie on or before date of randomisation, every 4 weeks post baseline, assessed maximum up to 27 months
measure: Time to Deterioration in QoL Dysphagia Domain Score in the Overall Study Population
timeFrame: Questionnaire data collected at Baseline ie on or before date of randomisation, every 4 weeks post baseline, assessed maximum up to 27 months
measure: Time to Deterioration in QoL Eating Restriction Domain Score in the Overall Study Population
timeFrame: Questionnaire data collected at Baseline ie on or before date of randomisation, every 4 weeks post baseline, assessed maximum up to 27 months
measure: Time to Deterioration in QoL Stomach Pain Domain Score in the Overall Study Population
timeFrame: Questionnaire data collected at Baseline ie on or before date of randomisation, every 4 weeks post baseline, assessed maximum up to 27 months
measure: Time to Deterioration in QoL Reflux Domain Score in the Overall Study Population
timeFrame: Questionnaire data collected at Baseline ie on or before date of randomisation, every 4 weeks post baseline, assessed maximum up to 27 months
measure: Time to Deterioration in QoL Anxiety Domain Score in the Overall Study Population
timeFrame: Questionnaire data collected at Baseline ie on or before date of randomisation, every 4 weeks post baseline, assessed maximum up to 27 months
Other outcomes:
Locations:
city: Goyang-si
country: Korea, Republic of
facility: Research Site
city: Jeonnam
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Taegu
country: Korea, Republic of
facility: Research Site
Study officials:
affiliation: AstraZeneca
name: Jane Robertson, BSc, MBCHB, MD
role: STUDY_DIRECTOR
affiliation: Seoul National University Hospital
name: Yung-Jue Bang, MD
role: PRINCIPAL_INVESTIGATOR
References: