Clinical trial NCT01735071: Bevacizumab and Trabectedin +/- Carboplatin in Advanced Ovarian Cancer
Official title: Multicenter, Randomized, Non-comparative, 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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Ovarian Epithelial Cancer Recurrent
Keywords: ovarian cancer
bevacizumab
trabectedin
carboplatin
randomized trial
phase II
Lead sponsor: Mario Negri Institute for Pharmacological Research
Sponsor class: OTHER
Collaborators: name: PharmaMar
name: Hoffmann-La Roche
First posted: 2012-11-28
Enrollment: 71
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a multicentre, randomized, non-comparative phase II study aimed at assessing efficacy and safety of two regimens according to a Bryant and Day two-stage design
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Progression Free Survival at 6 months (PFS-6)
timeFrame: from randomization up to 6 months
measure: Proportion of patients with severe toxicity within 6 months from randomization.
timeFrame: from randomization up to 6 months
Secondary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: from randomization up to 30 months
measure: Overall survival at 12 months (OS-12)
timeFrame: one year
measure: Clinical Benefit (CB)
timeFrame: from randomization up to 30 months
measure: Incidence of Adverse Events (AEs)
timeFrame: from randomization up to 30 months
measure: Maximum toxicity grade
timeFrame: from randomization up to 30 months
measure: Percentage of patients experiencing grade 3-4 toxicity for each specific toxicity
timeFrame: from randomization up to 30 months
measure: Patients with at least a Serious Adverse Drug Reaction (SADR)
timeFrame: from randomization up to 30 months
measure: Patients with at least a Suspect Unexpected Serious Adverse Reaction (SUSAR).
timeFrame: from randomization up to 30 months
measure: Percentage of patients with dose and/or time modifications
timeFrame: from randomization up to 30 months
measure: Percentage of premature withdrawals
timeFrame: from randomization up to 30 months
measure: Patients with at least a Serious Adverse Event (SAE)
timeFrame: from randomization up to 30 months
measure: Nature of AEs
timeFrame: from randomization up to 30 months
measure: Severity of AEs
timeFrame: from randomization up to 30 months
measure: Seriousness of AEs
timeFrame: from randomization up to 30 months
Other outcomes:
Locations:
city: Brescia
country: Italy
facility: Azienda Ospedaliera Spedali Civili di Brescia
city: Milano
country: Italy
facility: AO Fatebenefratelli e Oftalmico
city: Milan
country: Italy
facility: Istituto Europeo di Oncologia
city: Monza
country: Italy
facility: Azienda Ospedaliera S. Gerardo
city: Padova
country: Italy
facility: Istituto Oncologico Veneto
city: Roma
country: Italy
facility: Policlinico Universitario Agostino Gemelli di Roma
city: Torino
country: Italy
facility: Mauriziano Hospital
Study officials:
affiliation: IRCCS Istituto Europeo di Oncologia di Milano
name: Nicoletta Colombo, Medical D
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.