Assessment of Efficacy of AZD2281 in Platinum Sensitive Relapsed Serous Ovarian Cancer

Study Overview
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Brief Summary
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The primary purpose of this study to determine if AZD2281 is effective and well tolerated in maintaining the improvement in your cancer after previous platinum-based chemotherapy

Official Title
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Phase II Randomised, Double Blind, Multicentre Study to Assess the Efficacy of AZD2281 in the Treatment of Patients With Platinum Sensitive Relapsed Serous Ovarian Cancer Following Treatment With Two or More Platinum Containing Regimens

Conditions
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Ovarian Cancer

Intervention / Treatment
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* Drug: AZD2281
* Drug: matching placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female patients with histologically diagnosed serous ovarian cancer or recurrent serous ovarian cancer. Patients must have completed at least 2 previous courses of platinum containing therapy; the patient must have been platinum sensitive to the penultimate chemo regimen. For the last chemotherapy course prior to enrolment on the study, patients must have demonstrated an objective stable maintained response (partial or complete response) and this response needs to be maintained until completion of chemotherapy. Patients must be treated on the study within 8 wks of completion of their final dose of the platinum containing regimen. Exclusion Criteria: Previous treatment with PARP inhibitors including AZD2281 Patients with low grade ovarian carcinoma. Patients who have had drainage of their ascites during the final 2 cycles of their last chemotherapy regimen prior to enrolment on the study Patients receiving any chemotherapy, radiotherapy (except for palliative reasons), within 2 weeks from the last dose prior to study entry (or a longer period depending on the defined characteristics of the agents used).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 130 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>AZD2281 | Drug: AZD2281<br>* Tablets Oral BID<br>* Other names: Olaparib, Lynparza;|
| Placebo Comparator: 2<br>matching placebo | Drug: matching placebo<br>* matching placebo bid<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) (According to Response Evaluation Criteria in Solid Tumours [RECIST]) | PFS was defined as the time from randomisation to the earlier date of radiological progression (per RECIST criteria) or death by any cause in the absence of objective progression. [Full analysis set (FAS)] | Radiologic scans performed at baseline then every 12 weeks (+/- 1 week) for the first 60 weeks, then every 24 weeks (+/-1 week) thereafter, assessed maximum up to 14 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | OS = time from randomisation to date of death from any cause. Patients who had not died at time of analysis were censored at last date patient was known to be alive. | Follow up every 12 weeks post progression, assessed maximum up to 90 months. | 
| Objective Response Rate (ORR) (According to RECIST) | For each treatment group, the ORR was the number of Complete Response (CR) and Partial Response (PR) divided by the number of patients in the group in the FAS with measurable disease at baseline (displayed as a percentage below). Evaluable for response set | Radiologic scans performed at baseline then every 12 weeks (+/- 1 week) for the first 60 weeks, then every 24 weeks (+/-1 week) thereafter, assessed maximum up to 14 months. | 
| Disease Control Rate | Disease control rate was defined as the percentage of patients who have at least 1 confirmed visit response of CR or PR or have demonstrated SD or NED for at least 23 weeks (ie, 24 weeks +/- 1 week) prior to any evidence of progression. [FAS] | Assessed at 24 weeks. Radiologic scans performed at baseline, week 12 (+/- 1 week) and week 24 (+/- 1 week). | 
| Duration of Response | Duration of response = time from assessment prior to timepoint where PR or CR confirmed (i.e. initial assessment of PR/CR), until earliest date of objective progression or death. [Responding patients only]. There were insufficient responses to enable conclusions to be drawn. | Radiologic scans performed at baseline then every 12 weeks (+/- 1 week) for the first 60 weeks, then every 24 weeks (+/-1 week) thereafter, assessed maximum up to 14 months. | 
| Percentage Change From Baseline in Tumour Size at Week 24 | Percentage change from baseline to Week 24 in target tumour size. | Radiologic scans performed at baseline then every 12 weeks (+/- 1week) for the first 60 weeks, then every 24 weeks (+/-1 week) thereafter, assessed maximum up to 14 months. | 
| Best Percentage Change in Cancer Antigen 125 (CA-125) Levels | Best percentage change from baseline in CA-125 level | CA-125 was measured at baseline then every 28 days on treatment, assessed maximum up to 14 months. | 
| Best Objective Response | Best overall response from radiologic assessments. [FAS] | Radiologic scans performed at baseline then every 12 weeks (+/- 1week) for the first 60 weeks, then every 24 weeks (+/- 1 week) thereafter, assessed maximum up to 14 months. | 
| RECIST and CA-125 Response Separately and Combined | RECIST and CA-125 response separately and combined [Patients evaluable for either CA-125 response or RECIST response] | Radiologic scans performed at baseline then every 12 weeks (+/- 1week) for the first 60 weeks, then every 24 weeks (+/- 1 week) thereafter and monthly for CA-125 measurements, assessed maximum up to 14 months. | 
| Time to Earlier of CA-125 or RECIST Progression | Time from randomisation to the earlier date of radiological progression (per RECIST criteria) or CA-125 or death by any cause in the absence of objective progression. [FAS] | Radiologic scans performed at baseline then every 12 weeks (+/- 1 week) for the first 60 weeks, then every 24 weeks (+/- 1 week) thereafter and monthly for CA-125 measurements, assessed maximum up to 14 months. | 
| Improvement Rate for FACT-O Symptom Index (FOSI) | The percentage of patients with an improvement in FOSI. Improvement was defined as a change from baseline of greater than or equal to +3. [Evaluable for FOSI set] | Patient reported outcome questionnaire completed at baseline then every 28 days up to disease progression, assessed maximum up to 14 months. | 
| Improvement Rate for Trial Outcome Index (TOI) | The percentage of patients with an improvement in TOI. Improvement was defined as a change from baseline of greater than or equal to +7. [Evaluable for TOI set] | Patient reported outcome questionnaire completed at baseline then every 28 days up to disease progression, assessed maximum up to 14 months. | 
| Improvement Rate for Total Functional Analysis of Cancer Therapy - Ovarian (FACT-O) | The percentage of patients with an improvement in total FACT-O. Improvement was defined as a change from baseline of greater than or equal to +9. [Evaluable for FACT-O set] | Patient reported outcome questionnaire completed at baseline then every 28 days up to disease progression, assessed maximum up to 14 months. | 
| FACT-O Symptom Index (FOSI) Time to Worsening | The time to worsening was compared between treatments for each of the TOI, FOSI and total FACT-O. [Evaluable for FOSI set] | Patient reported outcome questionnaire completed at baseline then every 28 days up to disease progression, assessed maximum up to 14 months. | 
| Trial Outcome Index(TOI)Time to Worsening | The time to worsening was compared between treatments for each of the TOI, FOSI and total FACT-O. [Evaluable for TOI set] | Patient reported outcome questionnaire completed at baseline then every 28 days up to disease progression, assessed maximum up to 14 months. | 
| Functional Analysis of Cancer Therapy - Ovarian (FACT-O) Time to Worsening | The time to worsening was compared between treatments for each of the TOI, FOSI and total FACT-O. [Evaluable for FACT-O set] | Patient reported outcome questionnaire completed at baseline then every 28 days up to disease progression, assessed maximum up to 14 months. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Serous,, Ovarian cancer,, PARP,, BRCA1,, BRCA2,, Poly(ADP ribose) polymerases,, Platinum sensitive,, Homologous Recombination Deficiency (HRD)