Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

All Conditions

Immune System Diseases

Rare 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

Antineoplastic Agents

All Drugs and Chemicals

Olaparib

Poly(ADP-ribose) Polymerase Inhibitors

Enzyme Inhibitors

AZD2281

matching placebo

Mika Sovak, BSc, MBCHB, MD

Prof Jonathan A Lederman

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

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

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

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 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. \[Full analysis set (FAS)\]

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.

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

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. \[FAS\]

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.

Percentage change from baseline to Week 24 in target tumour size.

Best percentage change from baseline in CA-125 level

Best overall response from radiologic assessments. \[FAS\]

RECIST and CA-125 response separately and combined \[Patients evaluable for either CA-125 response or RECIST response\]

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. \[FAS\]

The percentage of patients with an improvement in FOSI. Improvement was defined as a change from baseline of greater than or equal to +3. \[Evaluable for FOSI set\]

The percentage of patients with an improvement in TOI. Improvement was defined as a change from baseline of greater than or equal to +7. \[Evaluable for TOI set\]

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. \[Evaluable for FACT-O set\]

The time to worsening was compared between treatments for each of the TOI, FOSI and total FACT-O. \[Evaluable for FOSI set\]

The time to worsening was compared between treatments for each of the TOI, FOSI and total FACT-O. \[Evaluable for TOI set\]

The time to worsening was compared between treatments for each of the TOI, FOSI and total FACT-O. \[Evaluable for FACT-O set\]

AstraZeneca

128 participants in Placebo as 1 participant withdrew consent prior to treatment

Olaparib 400 mg bd

Placebo

AZD2281 olaparib (AZD2281) 400 mg oral capsules twice daily

olaparib matching placebo oral capsules twice daily

Placebo bd

Total

Age, Continuous

Sex: Female, Male

>6 to 12 months

>12 months

The time to disease progression from the completion of the penultimate platinum containing therapy (last dose) prior to enrolment on the study.

Time to progression

Complete response

Partial response

Objective response to the last platinum containing regimen prior to enrolment on the study:

* CR-Complete Response (defined as normal radiological findings and CA-125 within the normal range)
* PR-Partial Response (defined as a RECIST PR and/or GCIG CA-125 response)

Objective response

For OM DoR: The subset of patients evaluable for response who responded to study treatment.Values in results table may be under-estimates as some patients had not progressed at final analysis,so true duration is likely to be greater than in database.

Global Clinical Lead

Progression Free Survival (PFS) (According to Response Evaluation Criteria in Solid Tumours [RECIST])

Overall Survival (OS)

Evaluable for response set - A subset of the full analysis set which includes patients with measurable disease at baseline

Objective Response Rate (ORR) (According to RECIST)

Disease Control Rate

Duration of Response

Evaluable for response set - A subset of the full analysis set which includes patients with measurable disease at baseline.

Percentage Change From Baseline in Tumour Size at Week 24

A subset of the FAS with baseline and at least 1 follow-up value of CA-125

Best Percentage Change in Cancer Antigen 125 (CA-125) Levels

Complete Response

Partial Response

No evidence of disease

Stable Disease >= 11 weeks

Disease Progression

Not Evaluable

Best Objective Response

RECIST Response

Confirmed RECIST Response

Unconfirmed RECIST response

CA-125 Response

Confirmed RECIST or CA-125 Response

RECIST and CA-125 Response Separately and Combined

Time to Earlier of CA-125 or RECIST Progression

Evaluable for FOSI set - A subset of the full analysis set which includes patients who have evaluable QoL/Symptom Endpoints at baseline

Improvement Rate for FACT-O Symptom Index (FOSI)

Evaluable for TOI - a subset of the full analysis set which includes patients who have evaluable QoL/Symptom Endpoints at baseline

Improvement Rate for Trial Outcome Index (TOI)

Evaluable for Total Fact-O set - A subset of the full analysis set which includes patients who have evaluable QoL/Symptom Endpoints at baseline

Improvement Rate for Total Functional Analysis of Cancer Therapy - Ovarian (FACT-O)

FACT-O Symptom Index (FOSI) Time to Worsening

Trial Outcome Index(TOI)Time to Worsening

Functional Analysis of Cancer Therapy - Ovarian (FACT-O) Time to Worsening

Overall Study

Symptoms and General Pathology

Recurrence

Fallopian Tube Neoplasms

Fallopian Tube Diseases

Fallopian Tube Cancer

Ramucirumab

Angiogenesis Inhibitors

Growth Inhibitors

Participants will receive ramucirumab at 8 milligrams/kilogram (mg/kg) administered over 1 hour every other week (every 14 days). Treatment will continue until there is evidence of disease progression, intolerable toxicity, or other withdrawal criteria are met.

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

The purpose of this study is to determine if ramucirumab given as monotherapy is effective in the treatment of Persistent or Recurrent Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Carcinoma.

Current chemotherapies used to treat ovarian cancer participants include doxorubicin, topotecan, and paclitaxel, to mention a few. Doxorubicin was studied in ovarian cancer participants that were refractory to paclitaxel and platinum-based chemotherapy agents. Inhibition of angiogenesis is considered a promising approach to the treatment of cancer. Vascular endothelial growth factor (VEGF) is an important regulator of angiogenesis and is likely an important therapeutic target in persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma. VEGF is overexpressed in ovarian tissue and may be the most important single tumor angiogenic factor. Phase 1 studies currently nearing completion with ramucirumab have demonstrated safety and tolerability at clinically relevant doses, with preliminary evidence of clinical efficacy in ovarian cancer participants. Therefore, ImClone Systems plans to conduct a Phase 2 trial to assess the safety and efficacy of ramucirumab in participants with platinum-refractory persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma.

Study of Ramucirumab in Ovarian Cancer

A Phase 2, Non-randomized, Open-label, Multicenter Study of IMC-1121B in the Treatment of Persistent or Recurrent Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Carcinoma

Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.

Data presented are the percentage of participants without progressive disease (PD) or death from any cause at 6 month after first dose. PD was determined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.0. PD is ≥20% increase in sum of longest diameter of target lesions and/or unequivocal progression of non-target lesion and/or new lesion.

Objective response is confirmed complete response (CR) + partial response (PR), as classified by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.0. CR is disappearance of all target and non-target lesions; PR is ≥30% decrease in sum of longest diameter of target lesions without new lesion and progression of non-target lesion. ORR is calculated as a total number of participants with CR or PR from the start of study treatment until disease progression/recurrence or the start of new therapeutic anticancer treatment, whichever occurred first, divided by the total number of participants treated, then multiplied by 100.

Defined as the time from date of first dose to the first observation of progression of disease (PD) or death due to any cause. PD was determined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.0. PD is ≥20% increase in sum of longest diameter of target lesions and/or unequivocal progression of non-target lesion and/or new lesion. For participants who had no PD or death or had started new therapeutic anticancer treatment, PFS was censored at their last radiographic tumor assessment.

Data presented are the percentage of participants surviving at least 12 months after first dose based on Kaplan Meier Method.

Overall survival is defined as the time from first dose to the date of death due to any cause. For participants who were alive or were lost to follow-up, overall survival was censored on the last date the participant was known to be alive.

Data presented are the number of participants who experienced treatment-emergent adverse events (TEAE), serious adverse events (SAE), Grade 3 or 4 TEAE, or adverse events (AE) leading to discontinuation of treatment that were considered to be related to ramucirumab. A summary of SAEs and other nonserious AEs, regardless of causality, is located in the Reported Adverse Events section.

Eli Lilly and Company

Deaths due to progressive disease are not considered adverse events (AE). Four deaths due to progressive disease were recorded by the investigator as serious AEs (SAE) and are captured in the SAE summary.

Ramucirumab at 8 milligrams/kilogram (mg/kg) administered intravenously over 1 hour every other week (every 14 days) of a 28-day cycle.

Age, Categorical

Ethnicity (NIH/OMB)

Black or African American

White

Other

Race/Ethnicity, Customized

United States

United Kingdom

Region of Enrollment

All participants who received any amount of study drug.

Chief Medical Officer

Percentage of Participants With Progression-Free Survival at 6 Months (PFS-6)

Objective Response Rate (ORR): Percentage of Participants With Complete Response (CR) and Partial Response (PR)

All participants who received any amount of study drug. The number of participants censored was 11.

Progression-Free Survival (PFS)

Overall Survival at 1 Year (OS-1)

All participants who received any amount of study drug. The number of participants censored was 12.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Assessment of Efficacy of AZD2281 in Platinum Sensitive Relapsed Serous Ovarian Cancer	NCT00753545	Ovarian Cancer	AZD2281 matching placeb...	18 Years - 130 Years	AstraZeneca
Study of Ramucirumab in Ovarian Cancer	NCT00721162	Ovarian Cancer Fallopian Tube ... Primary Periton...	Ramucirumab	18 Years -	Eli Lilly and Company

Spots Global Cancer Trial Database for ovarian cancer,