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Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Carcinoma

Disease Attributes

Endocrine Gland Neoplasms

Ovarian Diseases

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Genital Diseases

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Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

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Neoplasms by Histologic Type

Ovarian Cancer

Ovarian Epithelial Cancer

Antineoplastic Agents

All Drugs and Chemicals

Olaparib

Cediranib

Poly(ADP-ribose) Polymerase Inhibitors

Enzyme Inhibitors

Protein Kinase Inhibitors

Cediranib tablets oral dose 30 mg once daily; Olaparib(Lynparza) tablet 200 mg twice daily

Dose reduction for both products is allowed

cediranib and olaparib

Jung-Min Lee, M.D.

This is an open label, single arm, multi-center study to assess the efficacy and safety of the combination of cediranib and olaparib tablets in platinum-resistant relapsed high grade serous, high grade endometroid or clear cell ovarian, fallopian tube or primary peritoneal carcinoma patients who have received at least 3 prior lines of chemotherapy and who do not carry deleterious or suspected deleterious germline breast cancer susceptibility gene (BRCA) mutations.

The study will recruit approximately 60 patients aged ≥18 years, with histologically proven diagnosis of platinum-resistant relapsed high grade serous, high grade endometroid or clear cell ovarian, fallopian tube or primary peritoneal carcinoma who have received at least 3 prior lines of therapy, and who do not carry a deleterious or suspected deleterious germline BRCA mutation. All patients should have recurrent platinum resistant disease. The receipt of prior antiangiogenic treatment (e.g. bevacizumab) is optional. If used, it can be in the first line or recurrent setting. To be eligible to enter the study, all patients should have measurable disease (as assessed by the Investigator).

There is no maximum duration for taking the study treatments (cediranib+olaparib). Patients should continue on study treatments until objective radiological disease progression, as defined by RECIST version 1.1 guidelines, or they meet other discontinuation criteria. Following discontinuation of study treatment patients will be followed for disease progression (if they have not already progressed), survival and post-progression anti cancer therapies until the data cut-off for the primary analysis, approximately 8 months after enrollment of the last patient.

Efficacy and Safety Study of Cediranib in Combination With Olaparib in Patients With Recurrent Platinum-Resistant Ovarian Cancer

A Single Arm, Open-label, Phase IIb Study to Assess the Efficacy and Safety of the Combination of Cediranib and Olaparib Tablets in Women With Recurrent Platinum Resistant Epithelial Ovarian Cancer, Including Fallopian Tube and/or Primary Peritoneal Cancer Who do Not Carry a Deleterious or Suspected Deleterious Germline BRCA Mutation

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.

The ORR was defined as the percentage of patients with objective response (complete response \[CR\] or partial response \[PR\]) according to RECIST 1.1 and was assessed by ICR. Only patients whose CR/PR response was confirmed by a second scan at least 4 weeks after the initial response, with no evidence of progression between the initial and CR/PR confirmation visit were included.

CR: Disappearance of all target lesions (TLs) and non-TLs (NTLS) since baseline; any pathological lymph nodes selected as TLs must have a reduction in short axis to \<10 millimeters (mm).

PR: At least a 30% decrease in the sum of the diameters of TL, referencing the baseline sum of diameters.

Data obtained up until progression, or last evaluable assessment in the absence of progression were included in the assessment of ORR.

The percentage of patients with a response (CR/PR), including patients with both confirmed and unconfirmed responses, based on investigator assessed RECIST 1.1 data is presented. Confirmed responses included patients whose CR/PR response was confirmed by a second scan at least 4 weeks after the initial response, with no evidence of progression between the initial and CR/PR confirmation visit.

CR: Disappearance of all TLs and NTLs since baseline; any pathological lymph nodes selected as TLs must have a reduction in short axis to \<10 mm.

PR: At least a 30% decrease in the sum of the diameters of TL, referencing the baseline sum of diameters.

DoR was defined as the time from date of first documented response (which was subsequently confirmed) until date of documented progression or death in the absence of disease progression (i.e. date of progression free survival \[PFS\] event or censoring - date of first response + 1). The end of response coincided with the date of progression or death from any cause used for the PFS endpoint. The time of initial response was defined as the latest of the dates used towards the first visit that was CR or PR that was subsequently confirmed. If a patient did not progress following a response, the PFS censoring time was used. The Investigator assessment was based on the FAS and the ICR used the EFR analysis set. The median DoR for each assessment is presented and was calculated using the Kaplan-Meier technique.

The DCR was defined as the percentage of patients who had a best overall response of CR, PR or Stable Disease (SD) at 6 months.

CR: Disappearance of all TLs and NTLs since baseline; any pathological lymph nodes selected as TLs must have a reduction in short axis to \<10 mm.

PR: At least a 30% decrease in the sum of the diameters of TL, referencing the baseline sum of diameters.

SD: Neither sufficient shrinkage of TLs to qualify for PR nor sufficient increase to qualify for progressive disease (PD) (at least a 20% increase in the sum of diameters of TLs with an absolute increase of at least 5 mm and progression of existing NTLs). Patients had to have demonstrated SD for at least 23 weeks following the start of treatment. The Investigator assessment was based on the FAS and the ICR used the EFR analysis set. The percentage of patients with disease control for each assessment is presented.

PFS was defined as the time from date of first dose of IP until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdrew from treatment or received another anti-cancer therapy prior to progression (i.e. date of PFS event or censoring - date of first dose + 1). Patients who had not progressed or died at the time of analysis were censored at the time of the latest date of assessment from their last evaluable RECIST assessment.

The median PFS, calculated using the Kaplan-Meier technique, is presented for the ICR and the Investigator assessment, both based on the FAS.

The median time to discontinuation of IPs or death was defined as the time from the date of first dose of IP to the earlier of the date of discontinuation of both IPs, or death date. If 1 IP was discontinued before the other, the TDT reflected the time from the date of first dose to the earliest IP discontinuation date. The median TDT was calculated using the Kaplan-Meier technique.

OS was defined as the time from the date of first dose of IP until death due to any cause regardless of whether the patient withdrew from treatment or received another anti-cancer therapy (i.e. date of death or censoring - date of first dose + 1). Any patient not known to have died at the time of analysis was censored based on the last recorded date on which the patient was known to be alive. The median OS was calculated using the Kaplan-Meier technique.

The EORTC QLQ-C30 questionnaire assesses health-related quality of life (HRQoL). The questions are grouped into a global health status/QoL scale, 5 functional scales (physical, role, emotional, cognitive and social), 3 multi-item symptom scales (fatigue, pain, nausea/ vomiting), 5 single items assessing cancer symptoms (dyspnea, loss of appetite, insomnia, constipation, diarrhea), and 1 item on the financial impact of the disease.

Each scale/item is scored from 0 to 100. Higher scores on the global health status/QoL scale and functional scales indicate better health status/function. Higher scores on the symptom scales/items indicate a greater symptom burden.

A 10-point change in the score was used to identify patients who improved, stayed the same or deteriorated from baseline. The number of patients with a best observed change from baseline response of improved, stayed the same or deteriorated for each EORTC QLQ-C30 scale/item is presented.

The EORTC QLQ-OV28 is specific for ovarian cancer and consists of 28 items assessing abdominal/gastrointestinal symptoms (6 items), peripheral neuropathy (2 items), other chemotherapy side effects (5 items), hormonal symptoms (2 items), body image (2 items), attitudes to disease/treatment (3 items), sexuality (4 items) and 4 other single items.

Each scale was scored from 0 to 100 with higher scores on the symptom scales indicating greater symptom burden.

The best observed change from baseline is presented for each EORTC QLQ-OV28 scale, where a 10-point change in the score was used to identify patients who improved, stayed the same or deteriorated. The number of patients with a best observed change from baseline response of improved, stayed the same, or deteriorated in the EORTC QLQ-OV28 is presented.

Myriad Genetic Laboratories, Inc.

Merck Sharp & Dohme LLC

AstraZeneca

The safety analysis set included all patients who received at least 1 dose of either IP.

Patients received a combination of cediranib 30 mg orally qd and olaparib 200 mg orally bid until objective radiological disease progression, unacceptable toxicity or withdrawal of consent. Dose modification was allowed per protocol-defined guidelines.

Cediranib + Olaparib

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race/Ethnicity, Customized

The Full analysis set (FAS) included all patients who received at least 1 dose of either of the investigational products (IPs).

Global Clinical Lead

The evaluable for response (EFR) analysis set included all patients who received at least 1 dose of IP and had measurable disease at baseline according to the independent review of baseline imaging data. RECIST assessments were performed at baseline and every 8 weeks (+/- 1 week) after first doses of IPs until disease progression.

Mean Objective Response Rate (ORR) by Independent Central Review (ICR) Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

The FAS included all patients who received at least 1 dose of either of the IPs.

ORR by Investigator Assessment Using RECIST 1.1

ICR assessment (EFR analysis set)

Investigator assessment (FAS)

The EFR set included all patients who received at least 1 dose of IP and had measurable disease at baseline according to the independent review of baseline imaging data. The FAS included all patients who received at least 1 dose of either of the IPs.

Median Duration of Response (DoR) by ICR and Investigator Assessment Using RECIST 1.1

Disease Control Rate (DCR) by ICR and Investigator Assessment Using RECIST 1.1

ICR assessment (FAS)

Median PFS by ICR and Investigator Assessment Using RECIST 1.1

Median Time to Treatment Discontinuation or Death (TDT)

Median Overall Survival (OS)

Appetite loss: improved

Appetite loss: stayed the same

Appetite loss: deteriorated

Cognitive functioning: improved

Cognitive functioning: stayed the same

Cognitive functioning: deteriorated

Constipation: improved

Constipation: stayed the same

Constipation: deteriorated

Diarrhea: improved

Diarrhea: stayed the same

Diarrhea: deteriorated

Dyspnea: improved

Dyspnea: stayed the same

Dyspnea: deteriorated

Emotional functioning: improved

Emotional functioning: stayed the same

Emotional functioning: deteriorated

Fatigue: improved

Fatigue: stayed the same

Fatigue: deteriorated

Financial difficulties: improved

Financial difficulties: stayed the same

Financial difficulties: deteriorated

Global Health Status / QoL: improved

Global Health Status / QoL: stayed the same

Global Health Status / QoL: deteriorated

Insomnia: improved

Insomnia: stayed the same

Insomnia: deteriorated

Nausea / vomiting: improved

Nausea / vomiting: stayed the same

Nausea / vomiting: deteriorated

Pain: improved

Pain: stayed the same

Pain: deteriorated

Physical functioning: improved

Physical functioning: stayed the same

Physical functioning: deteriorated

Role functioning: improved

Role functioning: stayed the same

Role functioning: deteriorated

Social functioning: improved

Social functioning: stayed the same

Social functioning: deteriorated

The FAS included all patients who received at least 1 dose of either of the IPs. Only patients with non-missing baseline and post-baseline data were included in the analysis.

Best Observed Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) C30 Scales

Abdominal / Gastrointestinal: improved

Abdominal / Gastrointestinal: stayed the same

Abdominal / Gastrointestinal: deteriorated

Attitude to disease / treatment: improved

Attitude to disease / treatment: stayed the same

Attitude to disease / treatment: deteriorated

Body image: improved

Body image: stayed the same

Body image: deteriorated

Chemotherapy side effects: improved

Chemotherapy side effects: stayed the same

Chemotherapy side effects: deteriorated

Hormonal: improved

Hormonal: stayed the same

Hormonal: deteriorated

Other single items: improved

Other single items: stayed the same

Other single items: deteriorated

Peripheral neuropathy: improved

Peripheral neuropathy: stayed the same

Peripheral neuropathy: deteriorated

Sexuality: improved

Sexuality: stayed the same

Sexuality: deteriorated

Best Observed Change From Baseline in EORTC QLQ-OV28

Patients received a combination of cediranib 30 milligrams (mg) orally once daily (qd) and olaparib 200 mg orally twice daily (bid) until objective radiological disease progression, unacceptable toxicity or withdrawal of consent. Dose modification was allowed per protocol-defined guidelines.

Overall Study

Spots Global Cancer Trial Database for recurrent platinum resistant ovarian cancer