Bevacizumab and Trabectedin +/- Carboplatin in Advanced Ovarian Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Mario Negri Institute for Pharmacological Research
Sponsor:
Collaborators:
PharmaMar
Hoffmann-La Roche
Information provided by (Responsible Party):
Mario Negri Institute for Pharmacological Research
ClinicalTrials.gov Identifier:
NCT01735071
First received: November 13, 2012
Last updated: May 9, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Ovarian Epithelial Cancer Recurrent
Drug: bevacizumab and trabectedin
Drug: bevacizumab, trabectedin and carboplatin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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.

Resource links provided by NLM:


Further study details as provided by Mario Negri Institute for Pharmacological Research:

Primary Outcome Measures:
  • Progression Free Survival at 6 months (PFS-6) [ Time Frame: from randomization up to 6 months ] [ Designated as safety issue: No ]
    The PFS-6, defined as the percentage of patients who are alive and progression free at 6 months after the randomization.

  • Proportion of patients with severe toxicity within 6 months from randomization. [ Time Frame: from randomization up to 6 months ] [ Designated as safety issue: Yes ]

    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


Secondary Outcome Measures:
  • Progression Free Survival (PFS) [ Time Frame: from randomization up to 30 months ] [ Designated as safety issue: No ]
    Defined for each patient as the time from the date of randomization to the date of first progression, second primary malignancy or death for any cause, whichever comes first. Subjects not progressed or died at the time of the analysis will be censored at the last disease assessment date.

  • Overall survival at 12 months (OS-12) [ Time Frame: one year ] [ Designated as safety issue: No ]
    Defined as the percentage of patients who are alive at 12 months after the randomization.

  • Clinical Benefit (CB) [ Time Frame: from randomization up to 30 months ] [ Designated as safety issue: No ]
    clinical benefit, defined as the percentage of patients who are judged by the Investigators to have a complete response (CR), or partial response (PR) or stable disease (SD) according to the Response Evaluation Criteria In Solid Tumors (RECIST) criteria, version 1.1 after 12 weeks from the date of randomization.

  • Incidence of Adverse Events (AEs) [ Time Frame: from randomization up to 30 months ] [ Designated as safety issue: Yes ]
    Incidence of AEs, according to NCI-CTCAE, version 4.0

  • Maximum toxicity grade [ Time Frame: from randomization up to 30 months ] [ Designated as safety issue: Yes ]
    Maximum toxicity grade experienced by each patient for each specific toxicity

  • Percentage of patients experiencing grade 3-4 toxicity for each specific toxicity [ Time Frame: from randomization up to 30 months ] [ Designated as safety issue: Yes ]
    Percentage of patients experiencing grade 3-4 toxicity for each specific toxicity during the study

  • Patients with at least a Serious Adverse Drug Reaction (SADR) [ Time Frame: from randomization up to 30 months ] [ Designated as safety issue: Yes ]
    Patients with at least a SADR during the study

  • Patients with at least a Suspect Unexpected Serious Adverse Reaction (SUSAR). [ Time Frame: from randomization up to 30 months ] [ Designated as safety issue: Yes ]
    Patients with at least a suspect unexpected serious adverse reaction during the study

  • Percentage of patients with dose and/or time modifications [ Time Frame: from randomization up to 30 months ] [ Designated as safety issue: No ]
    Percentage of patients with dose and/or time modifications of the study drugs

  • Percentage of premature withdrawals [ Time Frame: from randomization up to 30 months ] [ Designated as safety issue: No ]
    Percentage of premature withdrawals of the enrolled patients

  • Patients with at least a Serious Adverse Event (SAE) [ Time Frame: from randomization up to 30 months ] [ Designated as safety issue: Yes ]
    Patients with at least a SAE during the study

  • Nature of AEs [ Time Frame: from randomization up to 30 months ] [ Designated as safety issue: Yes ]
    Nature of AEs, according to NCI-CTCAE, version 4.0

  • Severity of AEs [ Time Frame: from randomization up to 30 months ] [ Designated as safety issue: Yes ]
    Severity of AEs, according to NCI-CTCAE, version 4.0

  • Seriousness of AEs [ Time Frame: from randomization up to 30 months ] [ Designated as safety issue: Yes ]
    Seriousness of AEs according to NCI-CTCAE, version 4.0


Estimated Enrollment: 74
Study Start Date: July 2013
Estimated Study Completion Date: April 2015
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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
Drug: 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
Other Names:
  • Avastin
  • Yondelis
Experimental: 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

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

Other Names:
  • Avastin
  • Yondelis
  • Carboplatin

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01735071

Contacts
Contact: Roldano Fossati, Medical D 00390239014467 roldano.fossati@marionegri.it
Contact: Chiara Gerardi, Chem Pharm D 00390239014649 chiara.gerardi@marionegri.it

Locations
Italy
Azienda Ospedaliera Spedali Civili di Brescia Recruiting
Brescia, Italy
Contact: Germana Tognon, Medical D       germanatognon@alice.it   
Principal Investigator: Germana Tognon, Medical D         
Istituto Europeo di Oncologia Recruiting
Milan, Italy
Contact: Nicoletta Colombo, Medical D       nicoletta.colombo@ieo.it   
Contact: Sara Boveri       sara.boveri@ieo.it   
Principal Investigator: Nicoletta Colombo, Medical D         
Azienda Ospedaliera S. Gerardo Not yet recruiting
Monza, Italy
Contact: Andrea Lissoni, Medical D       andreaalberto.lissoni@unimib.it   
Principal Investigator: Andrea Lissoni, Medical D         
Università di Pisa Not yet recruiting
Pisa, Italy
Contact: Angiolo Gadducci, Medical D       a.gadducci@obgyn.med.unipi.it   
Principal Investigator: Angiolo Gadducci, Medical D         
Azienda Ospedaliera S.Anna Not yet recruiting
Torino, Italy
Contact: Dionyssios Katsaros, Medical D       dhocc@libero.it   
Principal Investigator: Dionyssios Katsaros, Medical D         
Sponsors and Collaborators
Mario Negri Institute for Pharmacological Research
PharmaMar
Hoffmann-La Roche
Investigators
Principal Investigator: Nicoletta Colombo, Medical D IRCCS Istituto Europeo di Oncologia di Milano
  More Information

No publications provided

Responsible Party: Mario Negri Institute for Pharmacological Research
ClinicalTrials.gov Identifier: NCT01735071     History of Changes
Other Study ID Numbers: IRFMN-OVA-6152
Study First Received: November 13, 2012
Last Updated: May 9, 2014
Health Authority: Italy: The Italian Medicines Agency
Italy: Ethics Committee

Keywords provided by Mario Negri Institute for Pharmacological Research:
ovarian cancer
bevacizumab
trabectedin
carboplatin
randomized trial
phase II

Additional relevant MeSH terms:
Ovarian Neoplasms
Neoplasms, Glandular and Epithelial
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Neoplasms by Histologic Type
Trabectedin
Bevacizumab
Carboplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors

ClinicalTrials.gov processed this record on August 28, 2014