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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01063517
First received: February 4, 2010
Last updated: May 6, 2015
Last verified: May 2015
  Purpose

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


Condition Intervention Phase
Gastric Cancer
Drug: olaparib
Drug: paclitaxel
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Progression Free Survival (PFS) in the Overall Study Population [ Time Frame: 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 ] [ Designated as safety issue: Yes ]
    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.

  • Progression Free Survival (PFS) in Patients With Tumours Defined as Homologous Recombination Deficient by Loss of Ataxia-Telangiectasia Mutation (ATM) Protein [ATM Negative Patients] [ Time Frame: 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 ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Overall Survival (OS) in the Overall Study Population [ Time Frame: 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 ] [ Designated as safety issue: Yes ]
    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.

  • Overall Survival (OS) in ATM Negative Patients [ Time Frame: 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 ] [ Designated as safety issue: Yes ]
    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.

  • Objective Response Rate (ORR) in the Overall Study Population [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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).

  • Objective Response Rate (ORR) in the ATM Negative Patients [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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).

  • Percentage Change in Tumour Size at Week 8 in the Overall Study Population [ Time Frame: Tumour scans done at Baseline and week 8 ] [ Designated as safety issue: Yes ]
    Percentage change in tumour size from baseline to Week 8 calculated as 100 X (week 8 tumour size - baseline tumour size) / (baseline tumour size)

  • Percentage Change in Tumour Size at Week 8 in the ATM Negative Patients [ Time Frame: Tumour scans done at Baseline and week 8 ] [ Designated as safety issue: Yes ]
    Percentage change in tumour size from baseline to Week 8 calculated as 100 X (week 8 tumour size - baseline tumour size) / (baseline tumour size)

  • Time to Deterioration in Global Quality of Life (QoL) Score in the Overall Study Population [ Time Frame: Questionnaire data collected at Baseline ie on or before date of randomisation, every 4 weeks post baseline, assessed maximum up to 27 months ] [ Designated as safety issue: No ]
    Time calculated from randomisation till worsening of Global QoL score based on European Organisation for Research and Treatment of Cancer (EORTC) questionnaire data

  • Time to Deterioration in QoL Fatigue Score in the Overall Study Population [ Time Frame: Questionnaire data collected at Baseline ie on or before date of randomisation, every 4 weeks post baseline, assessed maximum up to 27 months ] [ Designated as safety issue: Yes ]
    Time calculated from randomisation till worsening of fatigue score based on European Organisation for Research and Treatment of Cancer (EORTC) questionnaire data

  • Time to Deterioration in QoL Nausea & Vomiting Domain Score in the Overall Study Population [ Time Frame: Questionnaire data collected at Baseline ie on or before date of randomisation, every 4 weeks post baseline, assessed maximum up to 27 months ] [ Designated as safety issue: Yes ]
    Time calculated from randomisation till worsening of nausea & vomiting domain score based on European Organisation for Research and Treatment of Cancer (EORTC) questionnaire data

  • Time to Deterioration in QoL Pain Domain Score in the Overall Study Population [ Time Frame: Questionnaire data collected at Baseline ie on or before date of randomisation, every 4 weeks post baseline, assessed maximum up to 27 months ] [ Designated as safety issue: Yes ]
    Time calculated from randomisation till worsening of pain domain score based on European Organisation for Research and Treatment of Cancer (EORTC) questionnaire data

  • Time to Deterioration in QoL Dysphagia Domain Score in the Overall Study Population [ Time Frame: Questionnaire data collected at Baseline ie on or before date of randomisation, every 4 weeks post baseline, assessed maximum up to 27 months ] [ Designated as safety issue: Yes ]
    Time calculated from randomisation till worsening of dysphagia domain score based on European Organisation for Research and Treatment of Cancer (EORTC) questionnaire data

  • Time to Deterioration in QoL Eating Restriction Domain Score in the Overall Study Population [ Time Frame: Questionnaire data collected at Baseline ie on or before date of randomisation, every 4 weeks post baseline, assessed maximum up to 27 months ] [ Designated as safety issue: Yes ]
    Time calculated from randomisation till worsening of eating restriction domain score based on European Organisation for Research and Treatment of Cancer (EORTC) questionnaire data

  • Time to Deterioration in QoL Stomach Pain Domain Score in the Overall Study Population [ Time Frame: Questionnaire data collected at Baseline ie on or before date of randomisation, every 4 weeks post baseline, assessed maximum up to 27 months ] [ Designated as safety issue: Yes ]
    Time calculated from randomisation till worsening of stomach pain domain score based on European Organisation for Research and Treatment of Cancer (EORTC) questionnaire data

  • Time to Deterioration in QoL Reflux Domain Score in the Overall Study Population [ Time Frame: Questionnaire data collected at Baseline ie on or before date of randomisation, every 4 weeks post baseline, assessed maximum up to 27 months ] [ Designated as safety issue: Yes ]
    Time calculated from randomisation till worsening of reflux domain score based on European Organisation for Research and Treatment of Cancer (EORTC) questionnaire data

  • Time to Deterioration in QoL Anxiety Domain Score in the Overall Study Population [ Time Frame: Questionnaire data collected at Baseline ie on or before date of randomisation, every 4 weeks post baseline, assessed maximum up to 27 months ] [ Designated as safety issue: Yes ]
    Time calculated from randomisation till worsening of anxiety domain score based on European Organisation for Research and Treatment of Cancer (EORTC) questionnaire data


Enrollment: 267
Study Start Date: February 2010
Estimated Study Completion Date: December 2015
Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Olaparib + paclitaxel
Drug: olaparib
100mg BID oral tablet continuous
Drug: paclitaxel
iv infusion 80mg/m2 on Day 1, 8 and 15 of a 28 day cycle
Other Name: Taxol
Active Comparator: 2
paclitaxel + placebo
Drug: paclitaxel
iv infusion 80mg/m2 on Day 1, 8 and 15 of a 28 day cycle
Other Name: Taxol
Drug: Placebo
100mg BID oral tablet to match olaparib tablet

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01063517

Locations
Korea, Republic of
Research Site
Anyang, Korea, Republic of
Research Site
Goyang-si, Korea, Republic of
Research Site
Jeonju, Korea, Republic of
Research Site
Jeonnam, Korea, Republic of
Research Site
Seongnam, Korea, Republic of
Research Site
Seoul, Korea, Republic of
Research Site
Taegu, Korea, Republic of
Sponsors and Collaborators
AstraZeneca
Investigators
Study Director: Jane Robertson, BSc, MBCHB, MD AstraZeneca
Principal Investigator: Yung-Jue Bang, MD Seoul National University Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01063517     History of Changes
Other Study ID Numbers: D0810C00039
Study First Received: February 4, 2010
Results First Received: January 13, 2015
Last Updated: May 6, 2015
Health Authority: Korea: Food and Drug Administration

Keywords provided by AstraZeneca:
Poly(ADP ribose)
polymerase (PARP)
Gastric cancer
olaparib
PARP inhibitor
ATM AZD2281
Ku0059436
Homologous Recombination deficiency (HRD)
Recurrent gastric cancer
metastatic gastric cancer

Additional relevant MeSH terms:
Stomach Neoplasms
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Neoplasms
Neoplasms by Site
Stomach Diseases
Paclitaxel
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses
Tubulin Modulators

ClinicalTrials.gov processed this record on June 30, 2015