Bevacizumab and Trabectedin +/- Carboplatin in Advanced Ovarian Cancer

NCT ID: NCT01735071

Last Updated: 2019-11-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 71 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-07-31
• Study Completion Date: 2018-03-18

Brief Summary

This study is aimed at assessing the efficacy and the safety of the combination of bevacizumab and trabectedin with or without carboplatin in adult women with epithelial ovarian cancer at first recurrence occurred 6-12 months after the end of the last (first or second) platinum-containing regimen. According to the Bryant and Day design the primary endpoints will be the proportion of progression-free patients at 6 months for the efficacy, and the proportion of patients with severe toxicity for the safety at the same time-point.

Conditions

Ovarian Epithelial Cancer Recurrent

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

bevacizumab and trabectedin

Arm A: bevacizumab (15 mg/kg) given as 1 hour infusion will be followed by trabectedin (1.1 mg/sqm) 3 hour iv infusion; to be repeated every 21 days until progression, unacceptable toxicity, patient or physician decision to discontinue, or death patients

Group Type: EXPERIMENTAL

bevacizumab and trabectedin

Intervention Type: DRUG

Arm A: bevacizumab (15 mg/kg) given as 1 hour infusion will be followed by trabectedin (1.1 mg/sqm) 3 hour iv infusion; to be repeated every 21 days until progression, unacceptable toxicity, patient or physician decision to discontinue, or death patients

bevacizumab, trabectedin and carboplatin

Arm B: cycle 1-6, bevacizumab given as 1 hour infusion will be followed by carboplatin area under curve 4 (AUC 4) and trabectedin 3 hour iv infusion.

Cycle 7- end of treatment, bevacizumab given as 1 hour infusion will be followed by trabectedin 3 hour iv infusion.

Patient enrolled in arm B will receive (cycle 1-6): trabectedin 0.8 mg/m2 ,carboplatin AUC 4 day 1 every 28 days and bevacizumab 10 mg/kg iv on day 1 and day 15.

From cycle 7 to disease progression, unacceptable toxicity, patient or physician decision to discontinue, or death patients will receive bevacizumab 15 mg/kg iv and trabectedin 1.1 mg/m2 day 1 every 21 days

Group Type: EXPERIMENTAL

bevacizumab, trabectedin and carboplatin

Intervention Type: DRUG

Arm B: cycle 1- 6, bevacizumab given as 1 hour infusion will be followed by carboplatin AUC 4 and trabectedin 3 hour iv infusion.

Cycle 7- end of treatment, bevacizumab given as 1 hour infusion will be followed by trabectedin 3 hour iv infusion.

Patient enrolled in arm B will receive (cycle 1-6): trabectedin 0.8 mg/m2 ,carboplatin AUC 4 day 1 every 28 days and bevacizumab 10 mg/kg iv on day 1 and day 15.

From cycle 7 to disease progression, unacceptable toxicity, patient or physician decision to discontinue, or death patients will receive bevacizumab 15 mg/kg iv and trabectedin 1.1 mg/m2 day 1 every 21 days

Interventions

bevacizumab and trabectedin

Arm A: bevacizumab (15 mg/kg) given as 1 hour infusion will be followed by trabectedin (1.1 mg/sqm) 3 hour iv infusion; to be repeated every 21 days until progression, unacceptable toxicity, patient or physician decision to discontinue, or death patients

Intervention Type: DRUG

bevacizumab, trabectedin and carboplatin

Arm B: cycle 1- 6, bevacizumab given as 1 hour infusion will be followed by carboplatin AUC 4 and trabectedin 3 hour iv infusion.

Cycle 7- end of treatment, bevacizumab given as 1 hour infusion will be followed by trabectedin 3 hour iv infusion.

Patient enrolled in arm B will receive (cycle 1-6): trabectedin 0.8 mg/m2 ,carboplatin AUC 4 day 1 every 28 days and bevacizumab 10 mg/kg iv on day 1 and day 15.

From cycle 7 to disease progression, unacceptable toxicity, patient or physician decision to discontinue, or death patients will receive bevacizumab 15 mg/kg iv and trabectedin 1.1 mg/m2 day 1 every 21 days

Intervention Type: DRUG

Other Intervention Names

Avastin; Yondelis; Avastin; Yondelis; Carboplatin

Eligibility Criteria

Inclusion Criteria

• Age≥18years
• Eastern Cooperative Oncology Group (ECOG)- performance status 0-2
• Cytological/histological diagnosis of epithelial ovarian cancer
• Progression free interval between 6-12 months (calculated from the first day of the last cycle of the previous last platinum-based chemotherapy until the date of progression confirmation through radiologic imaging)
• One or two previous platinum-based chemotherapy lines
• Measurable disease according to RECIST version 1.1
• Life expectancy ≥ 12 weeks
• Patients must be able to receive dexamethasone or its equivalent, as a premedication for trabectedin
• Written informed consents given before the enrolment according to International Conference on Harmonization/ Good Clinical Practice (ICH/GCP).

Exclusion Criteria

• Prior treatment with trabectedin
• Prior progression while on therapy containing bevacizumab or other vascular endothelial growth factor (VEGF) pathway-target therapy
• Pre-existing grade > 1 sensitive/motor neurologic disorder
• Current or recent (within 30 days of first study dosing) treatment with another investigational drug
• Surgery (including open biopsy) within 4 weeks prior to the first planned dose of bevacizumab
• Current or recent (within 10 days prior to the first study drug dose) use of full-dose oral or parenteral anticoagulant or thrombolytic agent for therapeutic purposes (except for line patency, in which case international normalized ratio (INR) must be maintained below 1.5). Post operative prophylaxis with low molecular weight heparin sc is allowed
• Inadequate bone marrow function: absolute neutrophil count (ANC): <1.5 x 109/l, or platelet count <100 x 109/l or haemoglobin <9 g/dl. Patients may be transfused to maintain haemoglobin values ≥9 g/dl
• Inadequate coagulation parameters: activated partial thromboplastin time (APTT) >1.5 x upper limit of normal (ULN) or INR >1.5
• Inadequate liver function, defined as: serum (total) bilirubin > ULN for the institution AST/serum glutamic-oxaloacetic transaminase (SGOT) or ALT/ serum glutamic-pyruvic transaminase (SGPT) >2.5 x ULN
• Inadequate renal function: serum creatinine >1.5 mg/dL or >132 micromol/L and urine dipstick for proteinuria > or = 2+ and >1g of protein in their 24-hour urine collection
• History or evidence of brain metastases or spinal cord compression
• Pregnant, breastfeeding women and women of child bearing potential, who do not agree to use a medically acceptable method of contraception through the treatment period and for 6 months after discontinuation of treatment
• History or evidence of thrombotic or hemorrhagic disorders; including cerebrovascular accident, stroke or transient ischemic attack or sub-arachnoid haemorrhage within 6 months prior to the first study treatment
• Uncontrolled hypertension (sustained systolic >150 mmHg and/or diastolic >100 mmHg despite antihypertensive therapy) or clinically significant (i.e. active) cardiovascular disease, including: myocardial infarction or unstable angina within 6 months prior to the first study treatment, New York Heart Association grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication
• History of bowel obstruction, including subocclusive disease, related to the underlying disease and history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess. Evidence of recto-sigmoid involvement by pelvic examination or bowel involvement on CT scan or clinical symptoms of bowel obstruction
• Non-healing wound, ulcer or bone fracture
• hepatitis C virus (HCV) positivity
• Other malignancy within the last 5 years, except for adequately treated carcinoma in situ of the cervix or squamous carcinoma of the skin, or adequately controlled limited basal cell skin cancer.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

PharmaMar

INDUSTRY

Sponsor Role: collaborator

Hoffmann-La Roche

INDUSTRY

Sponsor Role: collaborator

Mario Negri Institute for Pharmacological Research

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Nicoletta Colombo, Medical D

Role: PRINCIPAL_INVESTIGATOR

IRCCS Istituto Europeo di Oncologia di Milano

Locations

Azienda Ospedaliera Spedali Civili di Brescia

Brescia, , Italy

Istituto Europeo di Oncologia

Milan, , Italy

AO Fatebenefratelli e Oftalmico

Milan, , Italy

Azienda Ospedaliera S. Gerardo

Monza, , Italy

Istituto Oncologico Veneto

Padua, , Italy

Policlinico Universitario Agostino Gemelli di Roma

Roma, , Italy

Mauriziano Hospital

Torino, , Italy

Countries

Italy

References

Colombo N, Zaccarelli E, Baldoni A, Frezzini S, Scambia G, Palluzzi E, Tognon G, Lissoni AA, Rubino D, Ferrero A, Farina G, Negri E, Pesenti Gritti A, Galli F, Biagioli E, Rulli E, Poli D, Gerardi C, Torri V, Fossati R, D'Incalci M. Multicenter, randomised, open-label, non-comparative phase 2 trial on the efficacy and safety of the combination of bevacizumab and trabectedin with or without carboplatin in women with partially platinum-sensitive recurrent ovarian cancer. Br J Cancer. 2019 Oct;121(9):744-750. doi: 10.1038/s41416-019-0584-5. Epub 2019 Sep 20.

Reference Type: RESULT

PMID: 31537908 (View on PubMed)

Other Identifiers

IRFMN-OVA-6152

Identifier Type: -

Identifier Source: org_study_id