Neoplasms

Digestive System Diseases

All Conditions

Symptoms and General Pathology

Rare Diseases

Stomach Neoplasms

Recurrence

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Stomach Diseases

Stomach Cancer

Antineoplastic Agents

All Drugs and Chemicals

Paclitaxel

Albumin-Bound Paclitaxel

Olaparib

Poly(ADP-ribose) Polymerase Inhibitors

Tubulin Modulators

Antimitotic Agents

Enzyme Inhibitors

olaparib

iv infusion 80mg/m2 on Day 1, 8 and 15 of a 28 day cycle

paclitaxel

100mg BID oral tablet to match olaparib tablet

Placebo

Jane Robertson, BSc, MBCHB, MD

Yung-Jue Bang, MD

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.

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

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

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal.

All request will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

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.

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

Time calculated from randomisation till worsening of Global QoL score based on European Organisation for Research and Treatment of Cancer (EORTC) questionnaire data

Time calculated from randomisation till worsening of fatigue score based on European Organisation for Research and Treatment of Cancer (EORTC) questionnaire data

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 calculated from randomisation till worsening of pain domain score based on European Organisation for Research and Treatment of Cancer (EORTC) questionnaire data

Time calculated from randomisation till worsening of dysphagia domain score based on European Organisation for Research and Treatment of Cancer (EORTC) questionnaire data

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 calculated from randomisation till worsening of stomach pain domain score based on European Organisation for Research and Treatment of Cancer (EORTC) questionnaire data

Time calculated from randomisation till worsening of reflux domain score based on European Organisation for Research and Treatment of Cancer (EORTC) questionnaire data

Time calculated from randomisation till worsening of anxiety domain score based on European Organisation for Research and Treatment of Cancer (EORTC) questionnaire data

AstraZeneca

OLAPARIB 100MG BD + PACLITAXEL / OLAPARIB 200MG BD

PLACEBO 100MG BD + PACLITAXEL / PLACEBO 200MG BD

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.

Olaparib+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.

Placebo+Paclitaxel

Total

Age, Continuous

< 50 years

>=50 to <65 years

>= 65 years

Age, Customized

Sex: Female, Male

Asian

Other

Race/Ethnicity, Customized

Negative

Positive

Ataxia-Telangiectasia Mutation (ATM) protein testing

ATM status

Anitra Fielding

The analysis was performed using a Cox proportional hazards model with factors for treatment group, ATM status and gastrectomy (full, partial, none).

Full analysis set including all randomised patients

Progression Free Survival (PFS) in the Overall Study Population

The analysis was performed using a Cox proportional hazards model with factors for treatment group and gastrectomy (full, partial, none).

Full analysis set including randomised ATM negative patients

Progression Free Survival (PFS) in Patients With Tumours Defined as Homologous Recombination Deficient by Loss of Ataxia-Telangiectasia Mutation (ATM) Protein [ATM Negative Patients]

Overall Survival (OS) in the Overall Study Population

Overall Survival (OS) in ATM Negative Patients

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

Objective Response Rate (ORR) in the Overall Study Population

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

Objective Response Rate (ORR) in the ATM Negative Patients

Percentage Change in Tumour Size at Week 8 in the Overall Study Population

Percentage Change in Tumour Size at Week 8 in the ATM Negative Patients

Randomised patients having global score calculated at baseline and at least one post baseline visit

Time to Deterioration in Global Quality of Life (QoL) Score in the Overall Study Population

Randomised patients having fatigue score calculated at baseline and at least one post baseline visit

Time to Deterioration in QoL Fatigue Score in the Overall Study Population

Randomised patients having nausea \& vomiting domain score calculated at baseline and at least one post baseline visit

Time to Deterioration in QoL Nausea & Vomiting Domain Score in the Overall Study Population

Randomised patients having pain domain score calculated at baseline and at least one post baseline visit

Time to Deterioration in QoL Pain Domain Score in the Overall Study Population

Randomised patients having dysphagia domain score calculated at baseline and at least one post baseline visit

Time to Deterioration in QoL Dysphagia Domain Score in the Overall Study Population

Randomised patients having eating restriction domain score calculated at baseline and at least one post baseline visit

Time to Deterioration in QoL Eating Restriction Domain Score in the Overall Study Population

Randomised patients having stomach pain domain score calculated at baseline and at least one post baseline visit

Time to Deterioration in QoL Stomach Pain Domain Score in the Overall Study Population

Randomised patients having reflux domain score calculated at baseline and at least one post baseline visit

Time to Deterioration in QoL Reflux Domain Score in the Overall Study Population

Randomised patients having anxiety domain score calculated at baseline and at least one post baseline visit

Time to Deterioration in QoL Anxiety Domain Score in the Overall Study Population

Overall Study

Topotecan

Topoisomerase I Inhibitors

KU-0059436 (AZD2281)(PARP inhibitor)

James Cassidy

James Carmichael, BSc MBChB MD FRCP

The purpose of this study is to identify a safe and tolerable dose of the drug KU-0059436 that can be given in combination with topotecan chemotherapy in patients with advanced solid tumours

Study to Assess the Safety and Tolerability of a PARP Inhibitor in Combination With Topotecan

A Phase I, Open-Label, Study of the Safety and Tolerability of KU-0059436 and Topotecan in the Treatment of Patients With Advanced Solid Tumours

KuDOS Pharmaceuticals Limited

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Immune System Diseases

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Hypersensitivity

Carcinoma

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Ovarian Cancer

Ovarian Epithelial Cancer

Carboplatin

Olaparib is available as a film-coated tablet containing 150 mg or 100 mg of olaparib. Subjects will be administered study treatment orally at a dose recommended by Investigator.

Full dose: 300 mg twice daily (bid) or Reduced doses: 200 mg twice daily (bid) or 100 mg twice daily (bid).

The planned dose of 300 mg bid will be made up of two x 150 mg tablets twice daily, with 100 mg tablets used to manage dose reductions.

175mg/m2 iv for 6 cycles (18 weeks) day 1 of 21 day cycle

AUC6 iv for 6 cycles (18 weeks) day 1 of 21 day cycle

carboplatin

175mg/m2 iv for up to 6 cycles (18 weeks)

Drug: carboplatin

Amit Oza, MD

To compare the efficacy of olaparib in combination with paclitaxel and carboplatin (AUC4) when compared with carboplatin (AUC6) and paclitaxel alone in patients with advanced ovarian cancer.

Study to Compare the Efficacy and Safety of Olaparib When Given in Combination With Carboplatin and Paclitaxel, Compared With Carboplatin and Paclitaxel in Patients With Advanced Ovarian Cancer

A Phase II Open Label Randomised Comparative Multicentre Study to Compare the Efficacy and Tolerability of Olaparib in Combination With Paclitaxel and Carboplatin Versus Paclitaxel and Carboplatin Alone in Patients With Platinum Sensitive Advanced Serous Ovarian Cancer

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

PFS (based on independent central review) was defined as the time from randomisation until objective disease progression as defined by Response Evaluation Criteria In Solid Tumours (RECIST) v1.1 (≥20% increase in the sum of the diameters of target lesions from minimum, clinically significant progression in non-target lesions or the presence of a new lesion) or death (by any cause in the absence of progression).

OS was defined as the time from randomisation until death by any cause. Patients who had not died at the time of analysis were censored at the last date the patient was known to be alive.

The total tumour size was defined as the sum of the longest diameters of the target lesions. At week 9, the percentage change in tumour size was calculated as \[(week 9 sum of target lesions - baseline sum of target lesions)/baseline sum of target lesions\]\*100 for each patient. Imputations were used for missing data where possible.

Olaparib orally (po) (200mg bd Days 1-10 of a 21-day cycle) in combination with paclitaxel intravenous (iv) (175 mg/m2 Day 1 of a 21-day cycle) and carboplatin iv (AUC4 Day 1 of a 21-day cycle) for at least 4 cycles.

Followed by olaparib monotherapy maintenance (400mg bd continuous dosing)

Olaparib/Carboplatin AUC4/Paclitaxel

Paclitaxel iv (175mg/m2 Day 1 of a 21-day cycle) and carboplatin iv (AUC6 Day 1 of a 21-day cycle) for 6 cycles.

Followed by a post-completion phase in which no study treatment was administered

Carboplatin AUC6/Paclitaxel

< 50

≥ 50 - < 65

≥ 65

Number of prior platinum-containing treatment lines

PD > 6 to ≤ 12 months after completion

PD >12 months after completion

Time to disease progression on completion of the previous platinum therapy

Gerard Lynch

The null hypothesis for all efficacy analyses in this study is that there is no difference in treatment effects between olaparib in combination with carboplatin/paclitaxel compared with carboplatin/paclitaxel alone.

Progression Free Survival (PFS)

Overall Survival (OS)

FAS, but including only patients with target lesions at baseline

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Efficacy Study of Olaparib With Paclitaxel Versus Paclitaxel in Gastric Cancer Patients	NCT01063517	Gastric Cancer	olaparib paclitaxel Placebo	18 Years - 130 Years	AstraZeneca
Study to Assess the Safety and Tolerability of a PARP Inhibitor in Combination With Topotecan	NCT00516438	Malignant Solid...	KU-0059436 (AZD... Topotecan	18 Years -	AstraZeneca
Study to Assess the Safety and Tolerability of a PARP Inhibitor in Combination With Topotecan	NCT00516438	Malignant Solid...	KU-0059436 (AZD... Topotecan	18 Years -	AstraZeneca
Study to Compare the Efficacy and Safety of Olaparib When Given in Combination With Carboplatin and Paclitaxel, Compared With Carboplatin and Paclitaxel in Patients With Advanced Ovarian Cancer	NCT01081951	Ovarian Cancer	olaparib paclitaxel carboplatin paclitaxel Drug: carboplat...	18 Years - 125 Years	AstraZeneca

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