Bevacizumab and Trabectedin +/- Carboplatin in Advanced Ovarian Cancer

Condition(s) targeted: Ovarian Epithelial Cancer Recurrent

Intervention: bevacizumab and trabectedin (Drug); bevacizumab, trabectedin and carboplatin (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: Mario Negri Institute for Pharmacological Research

Official(s) and/or principal investigator(s):
Nicoletta Colombo, Medical D, Principal Investigator, Affiliation: IRCCS Istituto Europeo di Oncologia di Milano

Overall contact:
Roldano Fossati, Medical D, Phone: 00390239014467, Email: roldano.fossati@marionegri.it

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 first 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.

Official title: Multicenter, Randomized, Non-comparative, Open-label Phase II Trial on the Efficacy and Safety of the Combination of Bevacizumab and Trabectedin With or Without Carboplatin in Adult Women With Platinum Partially Sensitive Recurring Ovarian Cancer.

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome:

Progression Free Survival at 6 months (PFS-6)

Proportion of patients with severe toxicity within 6 months from randomization.

Secondary outcome:

Progression Free Survival (PFS)

Overall survival at 12 months (OS-12)

Clinical Benefit (CB)

Incidence of Adverse Events (AEs)

Maximum toxicity grade

Percentage of patients experiencing grade 3-4 toxicity for each specific toxicity

Patients with at least a Serious Adverse Drug Reaction (SADR)

Patients with at least a Suspect Unexpected Serious Adverse Reaction (SUSAR).

Percentage of patients with dose and/or time modifications

Percentage of premature withdrawals

Patients with at least a Serious Adverse Event (SAE)

Nature of AEs

Severity of AEs

Seriousness of AEs

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Female.

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).

- Only one previous platinum-based chemotherapy line

- 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

Roldano Fossati, Medical D, Phone: 00390239014467, Email: roldano.fossati@marionegri.it

Azienda Ospedaliera Spedali Civili di Brescia, Brescia, Italy; Recruiting
Germana Tognon, Medical D, Email: germanatognon@alice.it
Germana Tognon, Medical D, Principal Investigator

AO Fatebenefratelli e Oftalmico, Milano, Italy; Not yet recruiting
Gabriella Farina, Email: gabriella.farina@fbf.milano.it

Istituto Europeo di Oncologia, Milan, Italy; Recruiting
Nicoletta Colombo, Medical D, Email: nicoletta.colombo@ieo.it
Nicoletta Colombo, Medical D, Principal Investigator

Azienda Ospedaliera S. Gerardo, Monza, Italy; Recruiting
Andrea Lissoni, Medical D, Email: andreaalberto.lissoni@unimib.it
Andrea Lissoni, Medical D, Principal Investigator

Istituto Oncologico Veneto, Padova, Italy; Not yet recruiting
Ornella Nicoletto, Medical D.
Ornella Nicoletto, Medical D., Principal Investigator

Università di Pisa, Pisa, Italy; Withdrawn

Policlinico Universitario Agostino Gemelli di Roma, Roma, Italy; Active, not recruiting

Azienda Ospedaliera S.Anna, Torino, Italy; Withdrawn

Starting date: July 2013
Last updated: July 22, 2015