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NCT00976911

AURELIA: A Study of Avastin (Bevacizumab) Added to Chemotherapy in Patients With Platinum-resistant Ovarian Cancer

Completed Phase 3 Results posted Last updated 21 June 2022
What this trial tests

Phase 3 trial testing Bevacizumab in Ovarian Cancer in 361 participants. Completed in 9 July 2014.

Timeline
29 October 2009
Primary endpoint
9 July 2014
9 July 2014

Quick facts

Lead sponsorHoffmann-La Roche
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment361
Start date29 October 2009
Primary completion9 July 2014
Estimated completion9 July 2014
Sites117 locations across Bosnia and Herzegovina, France, Finland, Denmark, Greece, Italy, Netherlands, Belgium

Drugs / interventions tested

Conditions studied

Sponsor

Hoffmann-La Roche — full company profile →

Who can join

18 and older, female only, with Ovarian Cancer. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Participants With Disease Progression or Death (Data Cutoff 14 November 2011) Primary · Screening Visit, Every 8 weeks (or 9 weeks if receiving topotecan) until progression reported between day of first participant randomized (29 October 2009) until cutoff date of 14 November 2011

Progression free survival was defined as the time from the date of randomization to the first documented disease progression or death, whichever occurs first. Progression was based on tumour assessment made by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST) criteria (for participants with measurable disease), and for those with non-measurable disease presence or absence of lesions was noted.

GroupValue95% CI
Chemotherapy92.3
Chemotherapy + Bevacizumab78.8
Percentage of Participants With Best Overall Confirmed Objective Response of Complete Response (CR) or Partial Response (PR) Per Modified RECIST (Data Cutoff 14 November 2011) Secondary · Screening Visit, Every 8 weeks (or 9 weeks if receiving topotecan) until progression reported between day of first participant randomized (29 October 2009) until cutoff date of 14 November 2011

Objective Response was determined by the investigator using modified RECIST criteria, Version 1.0. An objective response was a complete or partial overall confirmed response as determined by investigators. CR defined as complete disappearance of all target and non-target lesions and no new lesions. PR defined as greater than or equal to (≥) 30 percent (%) decrease in the sum of appropriate diameters of all target measurable lesions, no progress in the non-measurable disease, and no new lesions. 95% CI computed using the normal approximation to the binomial distribution.

GroupValue95% CI
Chemotherapy12.57.1 – 17.9
Chemotherapy + Bevacizumab28.220.8 – 35.6
Duration of Objective Response (Data Cutoff 14 November 2011) Secondary · Screening Visit, Every 8 weeks (or 9 weeks if receiving topotecan) until progression reported between day of first participant randomized (29 October 2009) until cutoff date of 14 November 2011

For randomized participants who achieved an objective response per modified RECIST, duration of objective response was defined as the time from the date of the first occurrence of a CR or PR (whichever occurred first) until the date that progressive disease or death was documented (whichever occurred first). Participants who had an objective response and did not experience disease progression or death by the time of analysis were censored at the time of the last tumor assessment. Summaries of duration of objective response (median and percentiles) were estimated from Kaplan-Meier curves. 95% C

GroupValue95% CI
Chemotherapy5.43.81 – 9.23
Chemotherapy + Bevacizumab9.46.60 – 11.63
Percentage of Participants Who Died (Data Cutoff 25 January 2013) Secondary · Screening Visit, Every 8 weeks (or 9 weeks if receiving topotecan) until progression reported between day of first participant randomized (29 October 2009) until cutoff date of 25 January 2013
GroupValue95% CI
Chemotherapy75.8
Chemotherapy + Bevacizumab71.5
Progression Free Survival (PFS; Data Cutoff 14 November 2011) Primary · Screening Visit, Every 8 weeks (or 9 weeks if receiving topotecan) until progression reported between day of first participant randomized (29 October 2009) until cutoff date of 14 November 2011

PFS was defined as the time from the date of randomization to the first documented disease progression or death, whichever occurred first. Progression was based on tumor assessment made by the investigators according to the RECIST criteria (for participants with measurable disease), and for those with non-measurable disease presence or absence of lesions was noted. Time from randomization to occurrence of disease progression or death was measured in months. An event was defined as the earliest progressive disease or death that occurred on or before the cutoff date (14 November 2011), regardles

GroupValue95% CI
Chemotherapy3.42.10 – 3.75
Chemotherapy + Bevacizumab6.85.62 – 7.79
Overall Survival (Data Cutoff 25 January 2013) Secondary · Screening Visit, Every 8 weeks (or 9 weeks if receiving topotecan) until progression reported between day of first participant randomized (29 October 2009) until cutoff date of 25 January 2013

Duration of overall survival was defined as the time from randomization to death of any cause. Kaplan-Meier methodology was used. The OS data for participants for whom no death was captured in the clinical database were censored at the last time they were known to be alive. 95% CI was computed using the method of Brookmeyer and Crowley.

GroupValue95% CI
Chemotherapy13.311.89 – 16.43
Chemotherapy + Bevacizumab16.613.70 – 18.99
European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) Ovarian (OV) 28 Abdominal/Gastrointestinal (AB/GI) Symptom Scale - Percentage of Responders (Data Cutoff 14 November 2011) Secondary · Baseline and Weeks 8, 9, 16, 18, 24 and 30 (Data Cutoff 14 November 2011)

The EORTC OV-28 module is a questionnaire that focuses on issues specific to ovarian cancer. It assesses AB/GI symptoms, among others. Participants were asked to indicate the extent to which they experienced AB/GI symptoms in the week prior to assessment. Participants responded on a scale of 1-4 (1=not at all, 2=a little, 3=quite a bit, 4=very much) to the following: Did you have abdominal pain? Did you have a bloated feeling in your abdomen/stomach? Did you have problems with your clothes feeling too tight? Did you experience any change in bowel habit as a result of your disease or treatment?

Weeks 8/9
GroupValue95% CI
Chemotherapy19.011.3 – 29.1
Chemotherapy + Bevacizumab27.920.1 – 36.7
Weeks 16/18
GroupValue95% CI
Chemotherapy23.311.8 – 38.6
Chemotherapy + Bevacizumab26.717.8 – 37.4
Week 24
GroupValue95% CI
Chemotherapy22.77.8 – 45.4
Chemotherapy + Bevacizumab32.119.9 – 46.3
Week 30
GroupValue95% CI
Chemotherapy33.39.9 – 65.1
Chemotherapy + Bevacizumab28.615.7 – 44.6

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse Events (AEs) were recorded at every treatment visit and all follow-up visits until 2 months after the final follow-up visit (up to approximately 4 years).. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Chemotherapy
Serious: 49/181 (27%)
Deaths:
Chemotherapy + Bevacizumab
Serious: 56/179 (31%)
Deaths:

Serious adverse events (80 terms)

ReactionSystemChemotherapyChemotherapy + Bevacizumab
VomitingGastrointestinal disorders
SubileusGastrointestinal disorders
Abdominal painGastrointestinal disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
Pulmonary embolismRespiratory, thoracic and mediastinal disorders
IleusGastrointestinal disorders
HypertensionVascular disorders
NeutropeniaBlood and lymphatic system disorders
ConstipationGastrointestinal disorders
AscitesGastrointestinal disorders
General physical health deteriorationGeneral disorders
PyrexiaGeneral disorders
AnaemiaBlood and lymphatic system disorders
Small intestinal obstructionGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
FatigueGeneral disorders
Device related infectionInfections and infestations
InfectionInfections and infestations
PneumoniaInfections and infestations
DehydrationMetabolism and nutrition disorders
Vesical fistulaRenal and urinary disorders
Female genital tract fistulaReproductive system and breast disorders
Pleural effusionRespiratory, thoracic and mediastinal disorders
Pneumonia aspirationRespiratory, thoracic and mediastinal disorders
Febrile neutropeniaBlood and lymphatic system disorders
Other adverse events (23 terms — click to expand)

ReactionSystemChemotherapyChemotherapy + Bevacizumab
NeutropeniaBlood and lymphatic system disorders
FatigueGeneral disorders
AnaemiaBlood and lymphatic system disorders
Peripheral sensory neuropathyNervous system disorders
HypertensionVascular disorders
LeukopeniaBlood and lymphatic system disorders
Mucosal inflammationGeneral disorders
ProteinuriaRenal and urinary disorders
InfectionInfections and infestations
Palmar-plantar erythrodysaesthesia syndromeSkin and subcutaneous tissue disorders
Abdominal painGastrointestinal disorders
ConstipationGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
NauseaGastrointestinal disorders
VomitingGastrointestinal disorders
Urinary tract infectionInfections and infestations
AlopeciaSkin and subcutaneous tissue disorders
Decreased appetiteMetabolism and nutrition disorders
ThrombocytopeniaBlood and lymphatic system disorders
Weight decreasedInvestigations
DyspnoeaRespiratory, thoracic and mediastinal disorders
Abdominal pain upperGastrointestinal disorders
EpistaxisRespiratory, thoracic and mediastinal disorders

Most-reported serious reactions: Vomiting, Subileus, Abdominal pain, Dyspnoea, Pulmonary embolism, Ileus, Hypertension, Neutropenia.

Data from ClinicalTrials.gov NCT00976911 adverse events section.

Sponsor's own description

This randomized, open-label, 2-arm study will evaluate the efficacy and safety of Avastin added to chemotherapy versus chemotherapy alone in patients with epithelial ovarian, fallopian tube or primary peritoneal cancer with disease progression within 6 months of platinum therapy. All patients will receive standard chemotherapy with either paclitaxel or topotecan or liposomal doxorubicin. Patients randomized to Arm 2 of the study will receive Avastin (10 mg/kg iv 2-weekly or 15 mg/kg iv 3-weekly) concomitantly. Anticipated time on study treatment is until disease progression. Patients will then receive standard of care, those in Arm 1 (chemotherapy only) may opt to receive Avastin (15 mg/kg iv 3-weekly). Target sample size is 100-500 individuals.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Meeting the challenge of ascites in ovarian cancer: new avenues for therapy and research.
    Kipps E, Tan DS, Kaye SB. · · 2013 · cited 441× · PMID 23426401 · DOI 10.1038/nrc3432
  2. Advances in ovarian cancer therapy.
    Cortez AJ, Tudrej P, Kujawa KA, Lisowska KM. · · 2018 · cited 417× · PMID 29249039 · DOI 10.1007/s00280-017-3501-8
  3. Tumor Microenvironment in Ovarian Cancer: Function and Therapeutic Strategy.
    Yang Y, Yang Y, Yang J, Zhao X, et al · · 2020 · cited 168× · PMID 32850861 · DOI 10.3389/fcell.2020.00758
  4. Anti-VEGF therapies in the clinic.
    Meadows KL, Hurwitz HI. · · 2012 · cited 165× · PMID 23028128 · DOI 10.1101/cshperspect.a006577
  5. Patient-reported outcome results from the open-label phase III AURELIA trial evaluating bevacizumab-containing therapy for platinum-resistant ovarian cancer.
    Stockler MR, Hilpert F, Friedlander M, King MT, et al · · 2014 · cited 123× · PMID 24687829 · DOI 10.1200/jco.2013.51.4240
  6. Targeted therapies in gynecological cancers: a comprehensive review of clinical evidence.
    Wang Q, Peng H, Qi X, Wu M, et al · · 2020 · cited 114× · PMID 32728057 · DOI 10.1038/s41392-020-0199-6
  7. Limitations in Clinical Trials Leading to Anticancer Drug Approvals by the US Food and Drug Administration.
    Hilal T, Gonzalez-Velez M, Prasad V. · · 2020 · cited 65× · PMID 32539071 · DOI 10.1001/jamainternmed.2020.2250
  8. Current Ovarian Cancer Maintenance Strategies and Promising New Developments.
    Gogineni V, Morand S, Staats H, Royfman R, et al · · 2021 · cited 54× · PMID 33391401 · DOI 10.7150/jca.49406

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Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT00976911.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing