Symptoms and General Pathology

All Conditions

Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Rare Diseases

Recurrence

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Ascites

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

Ovarian Cancer

Ovarian Epithelial Cancer

Antineoplastic Agents

All Drugs and Chemicals

Aflibercept

Angiogenesis Inhibitors

Growth Inhibitors

Participants with advanced ovarian epithelial cancer (including fallopian tube and primary peritoneal adenocarcinoma) treated with Aflibercept every 2 weeks until a criterion for treatment discontinuation was met

4.0 mg/kg administered intravenously (IV) once every 2 weeks

Aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®)

The primary objective of this study was to compare the time between paracenteses before and after administration of Aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®) in ovarian cancer participants with symptomatic malignant ascites.

The secondary objectives were to further assess efficacy and safety of Aflibercept treatment, and the exploratory objectives were to assess pharmacokinetics, immunogenicity and health-related quality of life.

The study consisted of:

* A 30-day screening phase prior to Day 1
* Day 1 registration and pre-treatment paracentesis
* Aflibercept administration within 1-day of registration
* Two-week study treatment cycles (for efficacy data, the cut-off date was 6 months post-registration
* A 60-day post-treatment follow-up phase

During the study, participants were treated with Aflibercept study treatment through the duration of the study unless they met one the following criteria for discontinuation:

* Participant (or legal representative) chose to withdraw from treatment
* The investigator or sponsor thought that continuation of the study would be detrimental to the participants well-being
* Participant had intercurrent illness that prevented further administration of investigational product (IP)
* Participant had more than 2 IP dose reductions
* Participant had unacceptable adverse events (AEs)
* Participant had arterial thromboembolic events, including cerebrovascular accidents, myocardial infarctions, transient ischemic attacks, new onset angina, or worsening of preexisting angina
* Participant required surgical intervention for intestinal obstruction or gastrointestinal perforation

AVE0005 (VEGF Trap) in Patients With Recurrent Symptomatic Malignant Ascites

A Multicenter, Open-label, Single-arm Study of the Efficacy and Safety of Intravenous AVE0005 (VEGF Trap) Administered Every 2 Weeks in Advanced Ovarian Cancer Patients With Recurrent Symptomatic Malignant Ascites

RPR was defined as at least a two-fold increase in the time to repeat paracentesis (TRP) as compared to the average duration of the 2 intervals between the 3 most recent paracenteses prior to study registration (ie, the baseline interval of paracentesis).

Percentage of participants with a repeat paracentesis response were the number of participants with RPR / number of total participants \* 100.

TRP is the number of days between the date of registration and the date of the first postregistration paracentesis. Median TRP was estimated from Kaplan-Meier curves. For participants who did not undergo a postregistration paracentesis while on study, TRP was censored at the end of the treatment period (last dose + 1 cycle), at the last visit known without repeat paracentesis, at 6 months postregistration, or at death, whichever was earlier.

FOP was the total number of paracenteses performed within the first 60 days postregistration. For participants who had withdrawn after registration but prior to the 60-day cutoff date, the withdrawal would have been regarded as a paracentesis event and the 60-day FOP normalized and calculated as the nearest integer of the value corresponding to 60 × number of paracenteses / x, where x represents the number of days on study.

According to the Response Evaluation Criteria in Solid Tumors \[RECIST\], progression was at least a 20% increase in the sum of the longest diameter (LD) of tumors, compared to smallest sum LD recorded since treatment started, or the appearance of one or more new tumors.

PFS time was interval from the date of registration to the date of tumor progression or death from any cause, whichever was earlier. Median PFS time was estimated from Kaplan-Meier Plots.

If participants were alive and progression-free at 6 months postregistration, they were censored for PFS.

OS time was the time interval between the date of registration to the date of death from any cause. Median OS was estimated from Kaplan-Meier curves. Participants who died after efficacy data cutoff date (6 months postregistration) were censored at the data cutoff date.

Anti-drug antibodies in participant's serum were measured using 2 different methods

* an Enzyme Linked Immunosorbent Assay (ELISA) in which the lower limit of detection (LLOD) was 238.4 ng/mL; and
* an Electrochemiluminescence-based, Bridging Assay in which the validated LLOD was about 5.4 ng/mL in the absence of aflibercept and about 25.2 ng/mL in the presence of 20 μg/mL of aflibercept.

Participants with detectable anti-drug antibodies by either method were considered to have a positive anti-drug antibody response.

All AEs regardless of seriousness or relationship to study treatment, spanning from the first administration of study treatment until 60 days after the last administration of study treatment, were recorded, and followed until resolution or stabilization. The number of participants with all treatment emergent adverse events (TEAE), serious adverse events (SAE), TEAE leading to death, and TEAE leading to permanent treatment discontinuation are reported.

Regeneron Pharmaceuticals

Sanofi

Participants with advanced ovarian epithelial cancer treated with 4.0 mg/kg Aflibercept every 2 weeks until a criterion for treatment discontinuation was met

Age Continuous

<65 years

>=65 years

Age, Customized

Sex: Female, Male

Caucasian

Race/Ethnicity, Customized

Primary tumor site - Ovaries

Time since initial cancer diagnosis

Serous

Endometrioid

Clear cell (mesonephroid)

Other

Missing data

Histology

Unknown

Moderately differentiated

Poorly differentiated

Histology grade

Prior anticancer surgeries,

Average of the two paracentesis intervals prior to the Day 1 paracentesis before registration.

Baseline interval of paracentesis

ECOG Score = 0

ECOG Score = 1

ECOG Score = 2

The ECOG score assesses how the disease affects a participant's daily living abilities. It ranges from 0-5, with 0 being the best and 5 being the worst outcome. "0" reflects a fully active participant, able to carry on all pre-disease performance without restriction. "1" reflects a participant restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature. "2" reflects an ambulatory participant, who is up and about more than 50% of waking hours, and capable of all self-care but unable to carry out any work activities.

Eastern Cooperative Oncology Group (ECOG) performance status score

Trial Transparency Team

Percentage of Participants With a Repeat Paracentesis Response (RPR)

All participants were analyzed. 8 had one or more paracentesis events. Participants with no paracentesis events were censored at the end of the treatment period (last dose + 1 cycle).

Time to Repeat Paracentesis (TRP)

60-day Frequency of Paracentesis (FOP)

Participants with a PFS event (tumor progression or death) were analyzed.

Progression-free Survival (PFS) Time

All participants were analyzed. 5 participants who died after efficacy data cutoff date (6 months postregistration) were censored at the data cutoff date.

Overall Survival (OS) Time

Participants who received at least part of 1 dose of aflibercept and had evaluable blood samples

Number of Participants With a Positive Anti-drug Antibody Response

With at least one TEAE

With at least one serious TEAE

With a TEAE leading to death

With a TEAE resulting in discontinuation

All participants who received at least part of 1 dose of the study treatment.

Safety - Number of Participants With Adverse Events (AE)

Overall Study

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Doxorubicin

Liposomal doxorubicin

Topotecan

Participants with advanced ovarian epithelial adenocarcinoma administered 2.0 mg/kg Aflibercept.

Participants with advanced ovarian epithelial adenocarcinoma administered 4.0 mg/kg Aflibercept.

Aflibercept 4.0 mg/kg administered intravenously (IV) over 1 hour once every 2 weeks.

Aflibercept could be reduced by 1 dose level ( to 2.0 mg/kg) or 2 dose levels (to 1.0 mg/kg) in case of uncontrolled hypertension or urinary protein \>3.5 g/24 hours. Intrapatient dose escalation was not to be permitted. Participants requiring more than 2 dose level reductions would be withdrawn from study treatment.

Aflibercept 2.0 mg/kg administered intravenously (IV) over 1 hour once every 2 weeks.

Aflibercept could be reduced by 1 dose level (to 1.0 mg/kg) or 2 dose levels (to 0.5 mg/kg) in case of uncontrolled hypertension or urinary protein \>3.5 g/24 hours. Intrapatient dose escalation was not to be permitted. Participants requiring more than 2 dose level reductions would be withdrawn from study treatment.

ICD CSD

This study evaluated outcomes in participants with advanced ovarian epithelial adenocarcinoma receiving aflibercept.

The primary objective was to compare the objective response rate of Aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®) 4.0 mg/kg and 2.0 mg/kg, administered intravenously (IV) every 2 weeks with historical control in participants with advanced ovarian epithelial (including fallopian tube and primary peritoneal) adenocarcinoma resistant to platinum and topotecan and/or liposomal doxorubicin.

The secondary objectives was to further assess efficacy, safety, pharmacokinetics, potential biological and pharmacogenomic markers of study drug activity, and health-related quality of life.

This study employed an Independent Review Committee (IRC) for radiological tumor assessments. For all tumor assessment-related efficacy variables, two analyses were performed: the primary analysis was based on Independent Review Committee (IRC) reviewed data and the secondary analysis was based on Investigator evaluation. If an endpoint was evaluated by the IRC, the IRC reviewed data is reported for this study.

The study included:

* A screening period for 21 days
* Randomization at baseline (Treatment was initiated with 5 days of randomization)
* A treatment period with 14-day study treatment cycles until a study withdrawal criterion was met
* A follow-up period up to 60 days after the end of treatment

Withdrawal criteria that led to treatment discontinuation were:

* The participant or their legally authorized representative requested to withdraw
* In the investigator's opinion, continuation of the study would be detrimental to the participant's well being, due to reasons such as disease progression, unacceptable toxicity, noncompliance, or logistical considerations.
* A specific request by the Sponsor
* Participant had intercurrent illness that prevented further administration of study treatment
* Participant had more than 2 aflibercept dose reductions
* Participant had arterial thromboembolic events, including cerebrovascular accidents, myocardial infarctions, transient ischemic attacks, new onset or worsening of pre-existing angina
* Participant had radiographic evidence of intestinal obstruction (e.g., dilated loops of bowel accompanied by air-fluid levels) or gastrointestinal perforation (e.g., presence of extraluminal gas) requiring surgical intervention
* Participant was lost to follow-up

After discontinuing treatment, participants remained on the study until the last post-treatment visit or until recovery of drug related toxicities, whichever was later.

Study of AVE0005 (VEGF Trap) in Patients With Chemoresistant Advanced Ovarian Cancer

A Multicenter, Randomized, Double-blind, Parallel-arm, Two-stage Study of the Efficacy and Safety of AVE0005 (VEGF Trap) Administered Intravenously Every 2 Weeks in Patients With Platinum-resistant and topotecan-and/or Liposomal Doxorubicin-resistant Advanced Ovarian Cancer

OR included Complete Response (CR) and Partial Response (PR). Per RECIST, CR was disappearance of all target or non-target lesions, or normalization of tumor marker levels (for non-target lesions) and PR was at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, with baseline sum LD as reference.

Tumors were assessed by an independent third-party core imaging laboratory evaluating the chest, abdomen, and pelvis by Computerized Tomography (CT) scans or Magnetic Resonance Imaging (MRI) scans; and responses were confirmed by repeat tumor imaging 4-6 weeks later.

CBR was defined as having a Stable disease (SD) for \>= 6 months or a confirmed OR (PR or CR). Based on RECIST:

* SD was neither a sufficient shrinkage of the target lesions to qualify for PR nor sufficient increase to qualify for Progressive disease (PD), the persistence of non-target lesions or the maintenance of tumor marker level above the normal limits (for non-target lesions)
* CR was the disappearance of all target or non-target lesions; and PR was at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, with reference to the baseline sum LD.

DR was defined as the time interval from the first documentation of CR or PR to the date of tumor progression (or disease progression) as determined by RECIST, or death from any cause, whichever was earlier.

Based on RECIST, progressive disease was at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started, the appearance of one or more new target or non-target lesions, or the unequivocal progression of existing non-target lesions.

TMRR was the proportion of evaluable participants achieving a cancer antigen -125 (CA-125) response based on GCIG definition. A response to CA-125 occurred if after two elevated levels before therapy there was at least a 50% decrease in a post-treatment serum sample, which was confirmed by an independent sample collected 21 days or later that was =\< 110% of the post-treatment serum sample.

TTP was defined as the time interval measured from the date of randomization to the date of tumor progression as determined by RECIST. TTP was estimated from Kaplan-Meier curves.

For a participant who did not reach tumor progression during study, the censoring date was the date of the last valid tumor burden assessment or the date of study cut-off, whichever was earlier. If the participant had no valid post-baseline tumor burden assessment due to early termination, the censoring date was the date of randomization.

TTMP was the time interval from the date of randomization to the date of tumor marker progression as was defined by GCIG for the evaluable participants. TTMP was estimated using Kaplan-Meier curves.

For a participant who did not reach tumor marker progression (TMP) during study, the censoring date was the date of the last valid tumor burden assessment or the date of study cut-off, whichever was earlier. If the participant had no valid post-baseline tumor burden assessment due to early termination, the censoring date was the date of randomization.

PFS was as the time interval measured from the date of randomization to the date of tumor progression as determined by RECIST or death from any cause, whichever was earlier.

The number of participants with tumor/disease progression are reported. Participants who did not reach tumor progression during study, or had no valid post-baseline tumor burden assessment due to early termination, were censored in the PFS analysis.

PFS was as the time interval measured from the date of randomization to the date of tumor progression as determined by RECIST or death from any cause, whichever was earlier. PFS was estimated using Kaplan-Meier curves.

For a participant who did not reach tumor progression during study, the censoring date was the date of the last valid tumor burden assessment or the date of study cut-off, whichever was earlier. If the participant had no valid post-baseline tumor burden assessment due to early termination, the censoring date was the date of randomization.

OS was the time interval between randomization and the date of death from any cause. OS was estimated using Kaplan-Meier curves

A participant was censored for the OS analysis if the participant were alive during the study. The censoring date was either at the date that the participant was last known to be alive or the date of study cut-off, whichever was earlier.

All AEs regardless of seriousness or relationship to study treatment, spanning from the first administration of study treatment until 30 days after the last administration of study treatment, were recorded, and followed until resolution or stabilization. The number of participants with all treatment emergent adverse events (TEAE), serious adverse events (SAE), TEAE leading to death, and TEAE leading to permanent treatment discontinuation are reported.

The FACT-O questionnaire consists of 38 scored questions (scored from 0-4) that address physical well-being, social/family well-being, emotional well-being, functional well-being and some additional concerns which relate specifically to ovarian cancer symptoms. For each question, higher scores reflect a better quality of life. The total FACT-O score ranges from 0-152, with 152 indicating the best outcome.

Safety population: All randomized participants who received at least part of one dose of study treatment.

Participants with advanced ovarian epithelial adenocarcinoma administered 2.0 mg/kg Aflibercept intravenously every two weeks

Aflibercept 2.0 mg/kg

Participants with advanced ovarian epithelial adenocarcinoma administered 4.0 mg/kg Aflibercept intravenously every two weeks

Aflibercept 4.0 mg/kg

Total

<35 years

>=35 to <45 years

>=45 to <55 years

>=55 to <65 years

>=65 to <75 years

>=75 years

Black

Asian, Oriental

Unknown or Not Reported

Simon's cohort: The first 67 evaluable participants, based on Simon's two-stage design that required 67 evaluable participants per group to maintain a targeted 80% power for Objective response rate versus historical controls.

Number of Participants With Confirmed Objective Response (OR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Based on the Analysis by an Independent Review Committee (IRC) - Simon's Cohort

Number of Participants With a Clinical Benefit Response (CBR) as Per RECIST Based on the Analysis by the IRC

Efficacy evaluable population: All participants with advanced ovarian epithelial carcinoma who were randomized, underwent baseline tumor assessment, and received at least part of one dose of aflibercept.

Duration of Response (DR) Based on the Analysis by an Independent Review Committee (IRC)

Randomized participants who received at least part of one dose of aflibercept, had a baseline tumor assessment, had a valid CA-125 assessment (requiring at least two pretreatment sample and 2 post-treatment samples), did not receive mouse antibodies and had no medical or surgical interference with their peritoneum or pleura in the previous 28 days.

Tumor Marker Response Rate (TMRR) Based on the Gynecologic Cancer Intergroup (GCIG) Definition

Time to Tumor Progression (TTP) as Per RECIST Based on the Analysis by the IRC

Participants with a valid assessment of CA-125 (requiring at least one pretreatment sample and 2 post-treatment samples).

Time to Tumor Marker (CA-125) Progression (TTMP)

With disease progression as the first event

Death without disease progression

Censored due to drop-out

Censored at study cut-off

Number of Participants With Disease Progression Events for Progression-free Survival (PFS) Analysis by the IRC.

Progression-free Survival (PFS) Time Based on Analysis by the IRC

Number of Participants With Confirmed Objective Response (OR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Based on the Analysis by the IRC - Efficacy Evaluable Population

With any TEAE

With any serious TEAE

With any TEAE leading to death

With TEAE leading to treatment discontinuation

Overall Safety - Number of Participants With Adverse Events (AE)

Baseline (N=97, N=104)

Change (baseline to Cycle 2-Day 14) (N=79, N=77)

All randomized participants who had evaluable FACT-O questionnaires.

Participant's Assessment of Health Related Quality of Life (HRQL) Using a by Using the Functional Assessment of Cancer Therapy-Ovarian (FACT-O) Questionnaire

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
AVE0005 (VEGF Trap) in Patients With Recurrent Symptomatic Malignant Ascites	NCT00396591	Ovarian Neoplas...	Aflibercept (zi...	18 Years -	Sanofi
Study of AVE0005 (VEGF Trap) in Patients With Chemoresistant Advanced Ovarian Cancer	NCT00327171	Neoplasms Cancer of the O...	Aflibercept (zi... Aflibercept (zi...	18 Years -	Sanofi

Spots Global Cancer Trial Database for angiogenesis inhibition