Evaluation of Optimal Treatment With Bevacizumab in Patients With Platinum-sensitive Recurrent Ovarian Cancer

Phase 3

Completed

• Conditions: Recurrent Platinum-sensitive Ovarian Cancer
• Interventions: Drug: Carboplatin; Drug: PLD; Biological: Bevacizumab

• Registration Number: NCT01837251
• Lead Sponsor: AGO Research GmbH

Brief Summary

Evaluation of the best therapeutic index for patients with platinum-sensitive ovarian cancer when treatment with bevacizumab and gemcitabine/carboplatin or with bevacizumab and PLD/carboplatin.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2013-04-16
• Study First Submitted QC: 2013-04-22
• Study First Posted: 2013-04-23
• Study Start: 2013-05
• Primary Completion: 2021-01
• Study Completion: 2021-01
• Status Verified: 2021-07
• Last Update Submitted: 2021-07-08
• Last Update Posted: 2021-07-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 682

Inclusion Criteria

1. Histologically confirmed diagnosis of epithelial ovarian carcinoma or fallopian tube carcinoma or primary peritoneal carcinoma
2. First disease recurrence >6 months after first-line platinum-based chemotherapy
3. Patients with measurable or non-measurable disease (RECIST v1.1) or CA 125 assessable disease (GCIG criteria) or histological proven diagnosis of relapse
4. In case of cytoreductive surgery for recurrence, patients must be able to commence cytotoxic chemo-therapy within 8 weeks after cytoreductive surgery
5. ECOG PS 0-2
6. Absolute Neutrophil Count >= 1.5 x 10^9/L; Platelets >= 100 x 10^9/L; Hemoglobin >= 9.5 g/dL
7. Patients not receiving anticoagulant medication who have an International Normalized Ratio <= 1.5 and an Activated ProThrombin Time <= 1.5 x ULN
8. Serum bilirubin <= 2 x ULN; Serum transaminases <= 2.5 x ULN (<= 5 x ULN in the presence of liver metastasis)
9. Serum creatinine < 1.6 mg/dL or creatinine clearance >= 40 mL/min; Glomerular filtration rate > 40 ml/min (estimates based on the Cockroft-Gault or Jelliffe formula); Urine dipstick for proteinuria < 2+. If urine dipstick is >= 2+, 24 hour urine collection must demonstrate <= 1 g of protein in 24 hours
10. Normal blood pressure or adequately treated and controlled hypertension (either systolic BP ≤ 140 mmHg and/or diastolic BP ≤ 90 mmHg)

Exclusion Criteria

1. Ovarian tumors of low malignant potential
2. Malignancies other than ovarian cancer within 5 years prior to randomization
3. Administration of other simultaneous chemotherapy drugs, any other anticancer therapy or anti-neoplastic hormonal therapy, or simultaneous radiotherapy during the trial treatment period
4. Any previous radiotherapy to the abdomen or pelvis
5. Known hypersensitivity to used chemotherapeutic agents in this trial and bevacizumab and its excipients, chinese hamster ovary cell products or other recombinant human or humanised antibodies
6. Current or recent chronic use of aspirin > 325 mg/day
7. Surgery (including open biopsy) within 4 weeks prior to anticipated first dose of Bevacizumab
8. History of VEGF therapy related abdominal fistula or gastrointestinal perforation
9. Current, clinically relevant bowel obstruction, including sub-occlusive disease, related to underlying disease
10. Patients with evidence of abdominal free air not explained by paracentesis or recent surgical procedure
11. Previous Cerebro-Vascular Accident , Transient Ischaemic Attack or Sub-Arachnoid Haemorrhage
12. Prior history of hypertensive crisis or hypertensive encephalopathy
13. Clinically significant disease, including: myocardial infarction or unstable angina within ≤ 6 months of randomization; New York Heart Association (NYHA) >= grade 2 Congestive Heart Failure; poorly controlled cardiac arrhythmia despite medication; peripheral vascular disease grade >= 3
14. LVEF defined by ECHO/MUGA below the institutional lower limit of normal
15. Significant traumatic injury during 4 weeks prior to randomization
16. Current brain metastases or spinal cord compression
17. History or evidence upon neurological examination of central nervous system disease
18. Non-healing wound, active ulcer or bone fracture
19. History or evidence of thrombotic or hemorrhagic disorders within 6 months prior to randomization
20. Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic coagulation)
21. Fertile woman of childbearing potential not willing to use adequate contraception (oral contraceptives, intrauterine device or barrier method of contraception in conjunction with spermicidal jelly or surgically sterile) for the duration of the trial and at least 6 months afterwards
22. Pregnant or lactating women
23. Requirement of therapeutic anticoagulation using marcumar, warfarin or PTT-prolonging heparin

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Research Arm	PLD	Patients receive bevacizumab 10 mg/kg iv on day 1 \& 15 followed by PLD 30mg/m² iv on day 1 carboplatin AUC4 iv on day 1 every 4 weeks for up to 6 cycles in the absence of progression disease or unacceptable toxicities. Patients then continue to receive bevacizumab 15 mg/kg iv every 3 weeks until progression disease or unacceptable toxicities.
Research Arm	Bevacizumab	Patients receive bevacizumab 10 mg/kg iv on day 1 \& 15 followed by PLD 30mg/m² iv on day 1 carboplatin AUC4 iv on day 1 every 4 weeks for up to 6 cycles in the absence of progression disease or unacceptable toxicities. Patients then continue to receive bevacizumab 15 mg/kg iv every 3 weeks until progression disease or unacceptable toxicities.
Research Arm	Carboplatin	Patients receive bevacizumab 10 mg/kg iv on day 1 \& 15 followed by PLD 30mg/m² iv on day 1 carboplatin AUC4 iv on day 1 every 4 weeks for up to 6 cycles in the absence of progression disease or unacceptable toxicities. Patients then continue to receive bevacizumab 15 mg/kg iv every 3 weeks until progression disease or unacceptable toxicities.

Primary Outcome Measures

Name	Time	Method
investigator-determined progression-free survival	every 12 weeks until progression or up to 30 months (whichever occurs first)

Secondary Outcome Measures

Name	Time	Method
Health related Quality of Life (QoL)	Baseline and then every 12 weeks until investigator-determined progresssion-free survival and thereafter at every visit for th 5-years follow-up or death (whichever occurs first)
Safety and Tolerability, i.e. type, frequency, severity and duration o adverse reactions	every 3 weeks, 30 months after start of treatment or if applicable 4 weeks after last dose of bevacizumab (whichever occurs later)
Overall Survival	every 3 weeks during treatment with bevacizumab, thereafter every 6 months; for up 30 months
biological progression-free survival by serum CA 125	every 3 weeks until progression or up to 30 months (whichever occurs first)

Trial Locations

Locations (192)

Bankstown-Lidcombe Hospital; 🇦🇺 Bankstown, Australia

Chris O'Brien Lifehouse; 🇦🇺 Camperdown, Australia

NCCI - Coffs Harbour Hospital; 🇦🇺 Coffs Harbour, Australia

The Townsville Hospital; 🇦🇺 Douglas, Australia

Peninsula Health - Frankston Hospital; 🇦🇺 Frankston, Australia

Andrew Love Cancer Centre Geelong; 🇦🇺 Geelong, Australia

Royal Brisbane & Women's Hospital; 🇦🇺 Herston, Australia

Royal Hobart Hospital; 🇦🇺 Hobart, Australia

St. George Hospital; 🇦🇺 Kogarah, Australia

ICON Cancer Care Centre; 🇦🇺 Milton, Australia

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