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| ID | Type | Description | Link |
|---|---|---|---|
| EudraCT : 2005-005026-31 | |||
| AVE0005A /3001 |
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| Name | Class |
|---|---|
| Regeneron Pharmaceuticals | INDUSTRY |
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This study was designed to characterize the effect of aflibercept in participants with advanced chemoresistant ovarian cancer.
Primary objective: Compare the effect of aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®) to placebo treatment on repeat paracentesis in symptomatic malignant ascites in participants with advanced ovarian cancer
Secondary objectives: Safety, tolerability, paracentesis-related parameters, participant-reported outcome.
The study included:
Criteria for discontinuation included:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator | Participants with advanced ovarian cancer administered placebo in the double-blind (DB) period. In the open-label (OL) period, participants had the option to receive aflibercept or be withdrawn from the study. |
|
| Aflibercept | Experimental | Participants with advanced ovarian cancer administered aflibercept in the double-blind (DB) period. In the open-label (OL) period, participants had the option to continue to receive aflibercept or be withdrawn from the study. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®) | Drug | 4.0 mg/kg aflibercept was administered intravenously (IV) over 1 hour once every 2 weeks in the DB period. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Time to Repeat Paracentesis (TRP) | TRP was defined as the number of days between the date of randomization and the date of the first post-randomization paracentesis. For participants who did not undergo a postrandomization paracentesis on study, TRP was calculated from randomization to the end of the double-blind treatment period. | From Day 1 up to 6 months from randomization |
| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Curve (AUC) for Participant Assessed Ascites Impact Measure (AIM) | AIM 4 symptoms (abdominal discomfort, abdominal bloating, abdominal pain, and ability to move normally) are scored from 0 to 5, where higher scores represent worst outcomes. An AIM total score ranges from 0-20. A plot for (The AIM questionnaire total score - Baseline score) versus time were generated. AIM AUC represents the overall improvement (scored positive) if the area is below the baseline value or worsening (scored negative) if the area is above the baseline. AIM AUC for a participant is the sum of individual areas representing improvement (+) or worsening (-). |
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Participants who met the following criteria were eligible to participate in this study.
Inclusion Criteria:
Exclusion Criteria:
The above information is not intended to contain all considerations relevant to participation in a clinical trial.
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| Name | Affiliation | Role |
|---|---|---|
| Walter GOTLIEB | Director of Gynecologic Oncology and Colposcopy Associate Professor of Oncology, McGill University - Montreal - Quebec Canada | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Sanofi-Aventis Administrative Office | Bridgewater | New Jersey | 08807 | United States | ||
| Sanofi-Aventis Administrative Office |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37185961 | Derived | Gaitskell K, Rogozinska E, Platt S, Chen Y, Abd El Aziz M, Tattersall A, Morrison J. Angiogenesis inhibitors for the treatment of epithelial ovarian cancer. Cochrane Database Syst Rev. 2023 Apr 18;4(4):CD007930. doi: 10.1002/14651858.CD007930.pub3. | |
| 22192729 | Derived | Gotlieb WH, Amant F, Advani S, Goswami C, Hirte H, Provencher D, Somani N, Yamada SD, Tamby JF, Vergote I. Intravenous aflibercept for treatment of recurrent symptomatic malignant ascites in patients with advanced ovarian cancer: a phase 2, randomised, double-blind, placebo-controlled study. Lancet Oncol. 2012 Feb;13(2):154-62. doi: 10.1016/S1470-2045(11)70338-2. Epub 2011 Dec 20. |
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55 were randomized (started population). 3 participants were not randomized but they were treated, and permanently withdrawn from the study due to disease progression (1 participant), fatal disease progression (1 participant) and a treatment emergent adverse event (1 participant).
Fifty-eight (58) participants from a total of 23 sites in 7 countries were enrolled in the study.
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | Participants with advanced ovarian cancer administered placebo intravenously, once every two weeks in the DB period and 4.0 mg/kg aflibercept intravenously, once every two weeks in the OL period. |
| FG001 | Aflibercept |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Double Blind Treatment (DB) Period |
|
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| Placebo | Drug | Placebo was administered intravenously (IV) over 1 hour once every 2 weeks in the DB period. |
|
| aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®) | Drug | 4.0 mg/kg aflibercept was administered intravenously (IV) over 1 hour once every 2 weeks in the OL period. |
|
| From Day 1 up to 60 days from randomization to the first postrandomization paracentesis |
| 60-Day Frequency of Paracentesis (FOP) | 60-Day FOP was defined as the total number of paracenteses performed within the first 60 days after randomization during the double blind treatment period. | From Day 1 up to 60 days from randomization |
| Plasma Levels of Free and VEGF-bound Aflibercept | Free aflibercept and VEGF-bound aflibercept plasma concentrations were measured by separate enzyme-linked immunosorbent assay (ELISA). The limit of quantitation of free aflibercept was 15.6 ng/mL, and of VEGF-bound aflibercept was 43.9 ng/mL. Peak free aflibercept was estimated at the end of Cycle 1 (C1) administration. The median free and VEGF-bound trough concentrations were determined for each participant beyond Cycle 3 (C3), then mean values were estimated from these median values. | Following every biweekly treatment administration up to 60 days after treatment discontinuation |
| Vienna |
| Austria |
| Sanofi-Aventis Administrative Office | Diegem | Belgium |
| Sanofi-Aventis Administrative Office | Laval | Canada |
| Sanofi-Aventis Administrative Office | Budapest | Hungary |
| Sanofi-Aventis Administrative Office | Mumbai | India |
| Sanofi-Aventis Administrative Office | Netanya | Israel |
| Sanofi-Aventis Administrative Office | Barcelona | Spain |
| Sanofi-Aventis Administrative Office | Guildford Surrey | United Kingdom |
Participants with advanced ovarian cancer administered 4.0 mg/kg aflibercept intravenously, once every two weeks in the DB period and the OL period.
| SAFETY |
|
| COMPLETED |
|
| NOT COMPLETED |
|
|
| Open Label Treatment (OL) Period |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | Participants with advanced ovarian cancer administered placebo intravenously, once every two weeks in the DB period and 4.0 mg/kg aflibercept intravenously, once every two weeks in the OL period. |
| BG001 | Aflibercept | Participants with advanced ovarian cancer administered 4.0 mg/kg aflibercept intravenously, once every two weeks in the DB period and the OL period. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Baseline characteristics are reported for the randomized population | Number | participants |
| ||||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| |||||||||||||||||||
| Race/Ethnicity, Customized | Number | participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Time to Repeat Paracentesis (TRP) | TRP was defined as the number of days between the date of randomization and the date of the first post-randomization paracentesis. For participants who did not undergo a postrandomization paracentesis on study, TRP was calculated from randomization to the end of the double-blind treatment period. | The intent-to-treat (ITT) population - all participants who were randomized in the study. | Posted | Least Squares Mean | Standard Error | days | From Day 1 up to 6 months from randomization |
|
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Area Under the Curve (AUC) for Participant Assessed Ascites Impact Measure (AIM) | AIM 4 symptoms (abdominal discomfort, abdominal bloating, abdominal pain, and ability to move normally) are scored from 0 to 5, where higher scores represent worst outcomes. An AIM total score ranges from 0-20. A plot for (The AIM questionnaire total score - Baseline score) versus time were generated. AIM AUC represents the overall improvement (scored positive) if the area is below the baseline value or worsening (scored negative) if the area is above the baseline. AIM AUC for a participant is the sum of individual areas representing improvement (+) or worsening (-). | The intent-to-treat (ITT) population - all participants who were randomized in the study, and had evaluable AIM scores. | Posted | Least Squares Mean | Standard Error | (units on a 4-symptom scale)*day | From Day 1 up to 60 days from randomization to the first postrandomization paracentesis |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | 60-Day Frequency of Paracentesis (FOP) | 60-Day FOP was defined as the total number of paracenteses performed within the first 60 days after randomization during the double blind treatment period. | The intent-to-treat (ITT) population - all participants who were randomized in the study. | Posted | Least Squares Mean | Standard Error | paracentesis | From Day 1 up to 60 days from randomization |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Plasma Levels of Free and VEGF-bound Aflibercept | Free aflibercept and VEGF-bound aflibercept plasma concentrations were measured by separate enzyme-linked immunosorbent assay (ELISA). The limit of quantitation of free aflibercept was 15.6 ng/mL, and of VEGF-bound aflibercept was 43.9 ng/mL. Peak free aflibercept was estimated at the end of Cycle 1 (C1) administration. The median free and VEGF-bound trough concentrations were determined for each participant beyond Cycle 3 (C3), then mean values were estimated from these median values. | The analysis was performed using the safety population with evaluable blood samples. 42 participants were evaluated. | Posted | Mean | Standard Deviation | μg/mL | Following every biweekly treatment administration up to 60 days after treatment discontinuation |
|
|
From treatment initiation to October 30, 2009
Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | Participants with advanced ovarian cancer administered placebo intravenously, once every two weeks in the DB period and 4.0 mg/kg aflibercept intravenously, once every two weeks in the OL period. | 18 | 25 | 22 | 25 | ||
| EG001 | Aflibercept | Participants with advanced ovarian cancer administered 4.0 mg/kg aflibercept intravenously, once every two weeks in the DB period and the OL period. | 27 | 30 | 28 | 30 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 12.0 |
| ||
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA 12.0 |
| ||
| Pancytopenia | Blood and lymphatic system disorders | MedDRA 12.0 |
| ||
| Cardiopulmonary failure | Cardiac disorders | MedDRA 12.0 |
| ||
| Pericardial effusion | Cardiac disorders | MedDRA 12.0 |
| ||
| Abdominal pain | Gastrointestinal disorders | MedDRA 12.0 |
| ||
| Ascites | Gastrointestinal disorders | MedDRA 12.0 |
| ||
| Colonic fistula | Gastrointestinal disorders | MedDRA 12.0 |
| ||
| Diarrhoea | Gastrointestinal disorders | MedDRA 12.0 |
| ||
| Gastric ulcer haemorrhage | Gastrointestinal disorders | MedDRA 12.0 |
| ||
| Intestinal obstruction | Gastrointestinal disorders | MedDRA 12.0 |
| ||
| Intestinal perforation | Gastrointestinal disorders | MedDRA 12.0 |
| ||
| Large intestinal obstruction | Gastrointestinal disorders | MedDRA 12.0 |
| ||
| Large intestine perforation | Gastrointestinal disorders | MedDRA 12.0 |
| ||
| Nausea | Gastrointestinal disorders | MedDRA 12.0 |
| ||
| Obstruction gastric | Gastrointestinal disorders | MedDRA 12.0 |
| ||
| Small intestinal obstruction | Gastrointestinal disorders | MedDRA 12.0 |
| ||
| Small intestinal perforation | Gastrointestinal disorders | MedDRA 12.0 |
| ||
| Vomiting | Gastrointestinal disorders | MedDRA 12.0 |
| ||
| Asthenia | General disorders | MedDRA 12.0 |
| ||
| Death | General disorders | MedDRA 12.0 |
| ||
| Disease progression | General disorders | MedDRA 12.0 |
| ||
| Fatigue | General disorders | MedDRA 12.0 |
| ||
| Multi-organ failure | General disorders | MedDRA 12.0 |
| ||
| Oedema peripheral | General disorders | MedDRA 12.0 |
| ||
| Pain | General disorders | MedDRA 12.0 |
| ||
| Pyrexia | General disorders | MedDRA 12.0 |
| ||
| Bile duct obstruction | Hepatobiliary disorders | MedDRA 12.0 |
| ||
| Abscess | Infections and infestations | MedDRA 12.0 |
| ||
| Fungal skin infection | Infections and infestations | MedDRA 12.0 |
| ||
| Pneumonia | Infections and infestations | MedDRA 12.0 |
| ||
| Sepsis | Infections and infestations | MedDRA 12.0 |
| ||
| Upper respiratory tract infection | Infections and infestations | MedDRA 12.0 |
| ||
| Hip fracture | Injury, poisoning and procedural complications | MedDRA 12.0 |
| ||
| Blood electrolytes abnormal | Investigations | MedDRA 12.0 |
| ||
| Anorexia | Metabolism and nutrition disorders | MedDRA 12.0 |
| ||
| Dehydration | Metabolism and nutrition disorders | MedDRA 12.0 |
| ||
| Failure to thrive | Metabolism and nutrition disorders | MedDRA 12.0 |
| ||
| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA 12.0 |
| ||
| Headache | Nervous system disorders | MedDRA 12.0 |
| ||
| Confusional state | Psychiatric disorders | MedDRA 12.0 |
| ||
| Renal failure acute | Renal and urinary disorders | MedDRA 12.0 |
| ||
| Aspiration | Respiratory, thoracic and mediastinal disorders | MedDRA 12.0 |
| ||
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 12.0 |
| ||
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA 12.0 |
| ||
| Pleuritic pain | Respiratory, thoracic and mediastinal disorders | MedDRA 12.0 |
| ||
| Pneumonia aspiration | Respiratory, thoracic and mediastinal disorders | MedDRA 12.0 |
| ||
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA 12.0 |
| ||
| Respiratory distress | Respiratory, thoracic and mediastinal disorders | MedDRA 12.0 |
| ||
| Hypertension | Vascular disorders | MedDRA 12.0 |
| ||
| Hypotension | Vascular disorders | MedDRA 12.0 |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 12.0 |
| ||
| Tachycardia | Cardiac disorders | MedDRA 12.0 |
| ||
| Abdominal distension | Gastrointestinal disorders | MedDRA 12.0 |
| ||
| Abdominal pain | Gastrointestinal disorders | MedDRA 12.0 |
| ||
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 12.0 |
| ||
| Constipation | Gastrointestinal disorders | MedDRA 12.0 |
| ||
| Diarrhoea | Gastrointestinal disorders | MedDRA 12.0 |
| ||
| Dyspepsia | Gastrointestinal disorders | MedDRA 12.0 |
| ||
| Nausea | Gastrointestinal disorders | MedDRA 12.0 |
| ||
| Oral pain | Gastrointestinal disorders | MedDRA 12.0 |
| ||
| Stomatitis | Gastrointestinal disorders | MedDRA 12.0 |
| ||
| Vomiting | Gastrointestinal disorders | MedDRA 12.0 |
| ||
| Asthenia | General disorders | MedDRA 12.0 |
| ||
| Chest pain | General disorders | MedDRA 12.0 |
| ||
| Fatigue | General disorders | MedDRA 12.0 |
| ||
| Gait disturbance | General disorders | MedDRA 12.0 |
| ||
| Mucosal inflammation | General disorders | MedDRA 12.0 |
| ||
| Oedema peripheral | General disorders | MedDRA 12.0 |
| ||
| Pyrexia | General disorders | MedDRA 12.0 |
| ||
| Nasopharyngitis | Infections and infestations | MedDRA 12.0 |
| ||
| Pneumonia | Infections and infestations | MedDRA 12.0 |
| ||
| Upper respiratory tract infection | Infections and infestations | MedDRA 12.0 |
| ||
| Urinary tract infection | Infections and infestations | MedDRA 12.0 |
| ||
| Weight decreased | Investigations | MedDRA 12.0 |
| ||
| Anorexia | Metabolism and nutrition disorders | MedDRA 12.0 |
| ||
| Dehydration | Metabolism and nutrition disorders | MedDRA 12.0 |
| ||
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA 12.0 |
| ||
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA 12.0 |
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| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA 12.0 |
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| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 12.0 |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 12.0 |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 12.0 |
| ||
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 12.0 |
| ||
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA 12.0 |
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| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 12.0 |
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| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 12.0 |
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| Dizziness | Nervous system disorders | MedDRA 12.0 |
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| Dysgeusia | Nervous system disorders | MedDRA 12.0 |
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| Headache | Nervous system disorders | MedDRA 12.0 |
| ||
| Confusional state | Psychiatric disorders | MedDRA 12.0 |
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| Insomnia | Psychiatric disorders | MedDRA 12.0 |
| ||
| Dysuria | Renal and urinary disorders | MedDRA 12.0 |
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| Pollakiuria | Renal and urinary disorders | MedDRA 12.0 |
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| Proteinuria | Renal and urinary disorders | MedDRA 12.0 |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 12.0 |
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| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA 12.0 |
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| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 12.0 |
| ||
| Dyspnoea exertional | Respiratory, thoracic and mediastinal disorders | MedDRA 12.0 |
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| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 12.0 |
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| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 12.0 |
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| Palmar-plantar erythrodysaesthesia syndrome | Skin and subcutaneous tissue disorders | MedDRA 12.0 |
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| Petechiae | Skin and subcutaneous tissue disorders | MedDRA 12.0 |
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| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 12.0 |
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| Rash | Skin and subcutaneous tissue disorders | MedDRA 12.0 |
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| Hypertension | Vascular disorders | MedDRA 12.0 |
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| Hypotension | Vascular disorders | MedDRA 12.0 |
|
The investigator shall have the right to independently publish study results from his site after a multicenter publication, or 12 months after the completion of the study by all sites. He must provide the sponsor a copy of any such publication derived from the study for review and comment at least 45 days (20 days) in advance of any submission, and delay publication till the approval of the publication is given in writing by the Sponsor (not to exceed ninety days).
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Trial Transparency Team | Sanofi | Contact-Us@sanofi.com |
| ID | Term |
|---|---|
| D010051 | Ovarian Neoplasms |
| D001201 | Ascites |
| ID | Term |
|---|---|
| D004701 | Endocrine Gland Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D010049 | Ovarian Diseases |
| D000291 | Adnexal Diseases |
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D005833 | Genital Neoplasms, Female |
| D014565 | Urogenital Neoplasms |
| D000091662 | Genital Diseases |
| D004700 | Endocrine System Diseases |
| D006058 | Gonadal Disorders |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
Not provided
Not provided
| ID | Term |
|---|---|
| C533178 | aflibercept |
Not provided
Not provided
Not provided
| Worsening dyspnea |
|
| Ongoing Treatment |
|
| Title | Measurements |
|---|---|
|
| >=45 to <55 years |
|
| >=55 to <65 years |
|
| >=65 to <75 years |
|
| >=75 years |
|
| Male |
|
| Black |
|
| Asian, Oriental |
|
| Units | Counts |
|---|---|
| Participants |
|
|
|
|
|
| Participants |
|
|