Bevacizumab and Trabectedin +/- Carboplatin in Advanced Ovarian Cancer
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ClinicalTrials.gov Identifier: NCT01735071 |
Recruitment Status :
Completed
First Posted : November 28, 2012
Last Update Posted : November 19, 2019
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Condition or disease | Intervention/treatment | Phase |
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Ovarian Epithelial Cancer Recurrent | Drug: bevacizumab and trabectedin Drug: bevacizumab, trabectedin and carboplatin | Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 71 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
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 |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
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. |
Actual Study Start Date : | July 2013 |
Actual Primary Completion Date : | March 18, 2018 |
Actual Study Completion Date : | March 18, 2018 |
Arm | Intervention/treatment |
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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
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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:
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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:
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- Progression Free Survival at 6 months (PFS-6) [ Time Frame: from randomization up to 6 months ]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 ]
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
- Progression Free Survival (PFS) [ Time Frame: from randomization up to 30 months ]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 ]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 ]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 ]Incidence of AEs, according to NCI-CTCAE, version 4.0
- Maximum toxicity grade [ Time Frame: from randomization up to 30 months ]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 ]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 ]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 ]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 ]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 ]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 ]Patients with at least a SAE during the study
- Nature of AEs [ Time Frame: from randomization up to 30 months ]Nature of AEs, according to NCI-CTCAE, version 4.0
- Severity of AEs [ Time Frame: from randomization up to 30 months ]Severity of AEs, according to NCI-CTCAE, version 4.0
- Seriousness of AEs [ Time Frame: from randomization up to 30 months ]Seriousness of AEs according to NCI-CTCAE, version 4.0
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, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | Female |
Accepts Healthy Volunteers: | No |
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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01735071
Italy | |
Azienda Ospedaliera Spedali Civili di Brescia | |
Brescia, Italy | |
AO Fatebenefratelli e Oftalmico | |
Milano, Italy | |
Istituto Europeo di Oncologia | |
Milan, Italy | |
Azienda Ospedaliera S. Gerardo | |
Monza, Italy | |
Istituto Oncologico Veneto | |
Padova, Italy | |
Policlinico Universitario Agostino Gemelli di Roma | |
Roma, Italy | |
Mauriziano Hospital | |
Torino, Italy |
Principal Investigator: | Nicoletta Colombo, Medical D | IRCCS Istituto Europeo di Oncologia di Milano |
Responsible Party: | Mario Negri Institute for Pharmacological Research |
ClinicalTrials.gov Identifier: | NCT01735071 |
Other Study ID Numbers: |
IRFMN-OVA-6152 |
First Posted: | November 28, 2012 Key Record Dates |
Last Update Posted: | November 19, 2019 |
Last Verified: | November 2019 |
ovarian cancer bevacizumab trabectedin |
carboplatin randomized trial phase II |
Ovarian Neoplasms Carcinoma, Ovarian Epithelial 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 Carcinoma Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Bevacizumab Carboplatin Trabectedin Antineoplastic Agents, Immunological Antineoplastic Agents Angiogenesis Inhibitors Angiogenesis Modulating Agents Growth Substances Physiological Effects of Drugs Growth Inhibitors Antineoplastic Agents, Alkylating |