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Bevacizumab Beyond Progression in Platinum Sensitive Ovarian Cancer (MITO16MANGO2b)

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ClinicalTrials.gov Identifier: NCT01802749
Recruitment Status : Unknown
Verified December 2016 by National Cancer Institute, Naples.
Recruitment status was:  Active, not recruiting
First Posted : March 1, 2013
Last Update Posted : December 21, 2016
Sponsor:
Collaborator:
Mario Negri Institute for Pharmacological Research
Information provided by (Responsible Party):
National Cancer Institute, Naples

Tracking Information
First Submitted Date  ICMJE February 27, 2013
First Posted Date  ICMJE March 1, 2013
Last Update Posted Date December 21, 2016
Study Start Date  ICMJE November 2013
Estimated Primary Completion Date December 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 28, 2013)
progression free survival [ Time Frame: 12 months ]
assessed by local Investigator
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01802749 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 28, 2013)
  • overall survival [ Time Frame: 12 months ]
  • number of complete or partial responses [ Time Frame: 6 months ]
    according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
  • worst grade toxicity per patient [ Time Frame: evaluated every 3 weeks up to 12 months ]
    according to Common Toxicity Criteria for Adverse Events v. 4.03
  • number of patients taking oral antidiabetic therapy [ Time Frame: at baseline ]
  • number of patients taking antithrombotic therapy [ Time Frame: at baseline ]
  • progression free survival [ Time Frame: 12 months ]
    as measured by independent central review
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: February 28, 2013)
  • predictive clinical factors for efficacy of bevacizumab [ Time Frame: 12 months ]
  • correlation of baseline plasma biomarker expression and clinical outcome [ Time Frame: 12 months ]
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Bevacizumab Beyond Progression in Platinum Sensitive Ovarian Cancer
Official Title  ICMJE Multicenter Phase III Randomized Study With Second Line Chemotherapy Plus or Minus Bevacizumab in Patients With Platinum Sensitive Epithelial Ovarian Cancer Recurrence After a Bevacizumab/Chemotherapy First Line
Brief Summary

Bevacizumab has been found to prolong progression free survival in first line, and more recently, in second line treatment for platinum sensitive ovarian cancer patients who had not received prior treatment with bevacizumab.

Recently reported data suggest that patients with colon cancer who receive bevacizumab in more than one line of therapy (beyond progression) have better results. In ovarian cancer, the role of bevacizumab administered in both first and second-line therapies needs to be defined.

This study aims to evaluate whether administering bevacizumab in combination with chemotherapy in second-line therapy to patients with recurrent ovarian cancer who have received first-line bevacizumab will be more effective than chemotherapy alone.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Recurrent Ovarian Cancer
Intervention  ICMJE
  • Drug: Bevacizumab
    Other Name: Avastin
  • Drug: Paclitaxel
  • Drug: Carboplatin
  • Drug: pegylated liposomal doxorubicin
    Other Name: Caelyx
  • Drug: Gemcitabine
Study Arms  ICMJE
  • Active Comparator: chemotherapy

    Combination chemotherapy with ONE of the following regimens:

    • PLD-C: Pegylated liposomal doxorubicin 30 mg/m2 + Carboplatin AUC (area under curve) 5 on day 1 every 4 weeks;
    • GEM-C: Gemcitabine 1000 mg/m2 on day 1, 8 every 21 + Carboplatin AUC of 4 on day 1 every 21 days;
    • PAC-C: Paclitaxel 175 mg/m2 on day 1, every 21 + Carboplatin AUC of 5 on day 1 every 21 days.
    Interventions:
    • Drug: Paclitaxel
    • Drug: Carboplatin
    • Drug: pegylated liposomal doxorubicin
    • Drug: Gemcitabine
  • Experimental: Chemotherapy and bevacizumab

    Combination chemotherapy AND bevacizumab with ONE of the following regimens:

    • PLD-C: Pegylated liposomal doxorubicin 30 mg/m2 + Carboplatin AUC 5 on day 1 every 4 weeks and Bevacizumab 10 mg/kg i.v. on Day 1 every 2 weeks;
    • GEM-C: Gemcitabine 1000 mg/m2 on day 1, 8 every 21 + Carboplatin AUC of 4 on day 1 every 21 days AND Bevacizumab 15 mg/kg i.v. on Day 1 every 3 weeks;L
    • PAC-C: Paclitaxel 175 mg/m2 on day 1, every 21 + Carboplatin AUC of 5 on day 1 every 21 days AND Bevacizumab 15 mg/kg i.v. on Day 1 every 3 weeks.

    Patients whose disease has not progressed after the initial six cycles of combination treatment will continue bevacizumab, at 15 mg/kg every 3 weeks until disease progression,unacceptable toxicity or patient withdrawn.

    Interventions:
    • Drug: Bevacizumab
    • Drug: Paclitaxel
    • Drug: Carboplatin
    • Drug: pegylated liposomal doxorubicin
    • Drug: Gemcitabine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Actual Enrollment  ICMJE
 (submitted: December 20, 2016)
406
Original Estimated Enrollment  ICMJE
 (submitted: February 28, 2013)
400
Estimated Study Completion Date  ICMJE July 2018
Estimated Primary Completion Date December 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Female patients ≥18 years of age.
  • Patients with histologically confirmed epithelial ovarian or fallopian tube carcinoma or primary peritoneal carcinoma, including mixed Mullerian Tumours
  • Recurrence or progression at least 6 months after the last chemotherapy cycle of a first line carboplatin + paclitaxel chemotherapy including bevacizumab (recurrence or progression might occur either during or after bevacizumab as maintenance)
  • Patients can be included if they have a RECIST progression, with either measurable or non-measurable disease
  • ECOG (Eastern Cooperative Oncology Group Performance) Status of 0-2.
  • Life expectancy of at least 12 weeks.
  • Signed informed consent obtained prior to initiation of any study-specific procedures and treatment as confirmation of the patient's awareness and willingness to comply with the study requirements including blood samples for molecular analyses.
  • Availability of tumour samples for molecular analyses from primary surgery (mandatory) and secondary surgery (when available)

Exclusion Criteria:

Cancer related

  • Ovarian tumours with low malignant potential (i.e. borderline tumours)
  • History or evidence of synchronous primary endometrial carcinoma, unless all of the following criteria related to the endometrial carcinoma are met:

    • stage ≤Ia
    • no more than superficial myometrial invasion
    • no lymphovascular invasion
    • not poorly differentiated (grade 3 or papillary serous or clear cell carcinoma).
  • 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.

Prior current or planned treatment:

  • More than one previous chemotherapy line
  • Previous therapy with other anti-angiogenetic agents different from bevacizumab.
  • Any prior radiotherapy to the pelvis or abdomen.
  • Surgery (including open biopsy) within 4 weeks prior to the first bevacizumab dose.Current or recent (within 10 days prior to the first study drug dose) use of full-dose oral or parenteral anticoagulants or thrombolytic agents 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.
  • Current or recent (within 30 days of first study dosing) treatment with any other investigational drug.

Laboratory:

  • Inadequate bone marrow function: ANC (absolute neutrophil count): <1500/mm3, or platelet count <100,000/mm3 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 (international normalized ratio) >1.5
  • Inadequate liver function, defined as:

    • serum (total) bilirubin >1.5 x ULN for the institution
    • AST/SGOT or ALT/SGPT > 2.5 x ULN.
  • Inadequate renal function, defined as:

    • serum creatinine >2.0 mg/dl or >177 micromol/l
    • urine dipstick for proteinuria >2+. Patients with ≥ 1+ proteinuria at baseline dipstick analysis should undergo a 24-hour urine collection and must demonstrate ≤1g of protein in their 24-hour urine collection.

Prior or concomitant conditions or procedures:

  • History or evidence of brain metastases or spinal cord compression.
  • Pregnant or lactating females.
  • History or evidence of thrombotic or haemorrhagic disorders; including cerebrovascular accident (CVA) / stroke or transient ischemic attack (TIA) or sub-arachnoid haemorrhage within ≤6 months prior to the first study treatment).
  • Uncontrolled hypertension (sustained systolic >150 mm Hg and/or diastolic >100 mm Hg 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 (NYHA) grade II or greater congestive heart failure (CHF)
  • serious cardiac arrhythmia requiring medication (with the exception of atrial fibrillation or paroxysmal supraventricular tachycardia)
  • peripheral vascular disease ≥grade 3 (i.e. symptomatic and interfering with activities of daily living requiring repair or revision).
  • History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess, or with signs of impending bowel obstruction within 6 months prior to the first study treatment.
  • Non-healing wound, ulcer or bone fracture. Patients with granulating incisions healing by secondary intention with no evidence of facial dehiscence or infection are eligible but require three weekly wound examinations.
  • Evidence of any other medical conditions (such as psychiatric illness, peptic ulcer, etc.), physical examination or laboratory findings that may interfere with the planned treatment, affect patient compliance or place the patient at high risk from treatment-related complications.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France,   Greece,   Italy,   Monaco,   Switzerland
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01802749
Other Study ID Numbers  ICMJE MITO-16 -MANGO-OV2b
2012-004362-17 ( EudraCT Number )
ENGOT-ov 17 ( Other Identifier: ENGOT )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Cancer Institute, Naples
Study Sponsor  ICMJE National Cancer Institute, Naples
Collaborators  ICMJE Mario Negri Institute for Pharmacological Research
Investigators  ICMJE
Principal Investigator: Sandro Pignata, M.D., Ph.D. National Cancer Institute, Naples
Principal Investigator: Nicoletta Colombo, M.D. European Institute of Oncology
Principal Investigator: Francesco Perrone, M.D., Ph.D. National Cancer Institute, Naples
Principal Investigator: Gennaro Daniele, M.D., Ph.D. National Cancer Institute, Naples
Principal Investigator: Roldano Fossati, M.D. Mario Negri Institute
Principal Investigator: Ciro Gallo, M.D. University of Campania "Luigi Vanvitelli"
Principal Investigator: Irene Floriani, Ph.D. Mario Negri Institute
PRS Account National Cancer Institute, Naples
Verification Date December 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP