Bevacizumab and Trabectedin +/- Carboplatin in Advanced Ovarian Cancer

NCT01735071 | Completed Phase 2

• 1 other identifier: IRFMN-OVA-6152
• Study Type: interventional
• Target: 71
• Locations: 1 country
• Sites: 7

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

Keywords

ovarian cancer; bevacizumab; trabectedin; carboplatin; randomized trial; phase II

Outcome Measures

Primary Outcomes (2)

• Progression Free Survival at 6 months (PFS-6)

  The PFS-6, defined as the percentage of patients who are alive and progression free at 6 months after the randomization.

  from randomization up to 6 months

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

  The following conditions will be considered as severe toxicity: * absolute neutrophil count (ANC) \< 0.5x109/L lasting \> 7 days and/or with fever * platelets \< 25x109/L * any other grade 3-4 (evaluated by the National Cancer Institute-Common Terminology Criteria for Adverse Events \[NCI-CTCAE\] version 4.0) non-hematological toxicities except for reversible nausea/vomiting, diarrhea, hypersensitivity reactions, and alanine aminotransferase (ALT) or aspartate aminotransferase (AST) elevation reversible to grade 1 by day 28 * any toxicity causing a delay of \>14 days in the following cycle

  from randomization up to 6 months

Secondary Outcomes (14)

• Progression Free Survival (PFS)

  from randomization up to 30 months

• Overall survival at 12 months (OS-12)

  one year

• Clinical Benefit (CB)

  from randomization up to 30 months

• Incidence of Adverse Events (AEs)

  from randomization up to 30 months

• Maximum toxicity grade

  from randomization up to 30 months

Study Arms (2)

bevacizumab and trabectedin

EXPERIMENTAL

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

Drug: bevacizumab and trabectedin

bevacizumab, trabectedin and carboplatin

EXPERIMENTAL

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

Drug: bevacizumab, trabectedin and carboplatin

Interventions

bevacizumab and trabectedin 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

Also known as: Avastin, Yondelis

bevacizumab and trabectedin

bevacizumab, trabectedin and carboplatin 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

Also known as: Avastin, Yondelis, Carboplatin

bevacizumab, trabectedin and carboplatin

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

• Mario Negri Institute for Pharmacological Research: lead
• PharmaMar: collaborator
• Hoffmann-La Roche: collaborator

Study Sites (7)

Azienda Ospedaliera Spedali Civili di Brescia

Brescia, Italy

Location

Istituto Europeo di Oncologia

Milan, Italy

Location

AO Fatebenefratelli e Oftalmico

Milan, Italy

Location

Azienda Ospedaliera S. Gerardo

Monza, Italy

Location

Istituto Oncologico Veneto

Padua, Italy

Location

Policlinico Universitario Agostino Gemelli di Roma

Roma, Italy

Location

Mauriziano Hospital

Torino, Italy

Location

Related Publications (1)

• 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.

  PMID: 31537908 RESULT

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

Bevacizumab; Trabectedin; Carboplatin

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Dioxoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetrahydroisoquinolines; Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coordination Complexes; Organic Chemicals

Study Officials

• Nicoletta Colombo, Medical D

  IRCCS Istituto Europeo di Oncologia di Milano

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: November 13, 2012
• First Posted: November 28, 2012
• Study Start: July 1, 2013
• Primary Completion: March 18, 2018
• Study Completion: March 18, 2018
• Last Updated: November 19, 2019

Record last verified: 2019-11

Locations

IT (7)