Bevacizumab Beyond Progression in Platinum Sensitive Ovarian Cancer (MITO16MANGO2b)

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by National Cancer Institute, Naples
Sponsor:
Collaborator:
Mario Negri Institute for Pharmacological Research
Information provided by (Responsible Party):
National Cancer Institute, Naples
ClinicalTrials.gov Identifier:
NCT01802749
First received: February 27, 2013
Last updated: April 10, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Recurrent Ovarian Cancer
Drug: Bevacizumab
Drug: Paclitaxel
Drug: Carboplatin
Drug: pegylated liposomal doxorubicin
Drug: Gemcitabine
Phase 3

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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute, Naples:

Primary Outcome Measures:
  • progression free survival [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    assessed by local Investigator


Secondary Outcome Measures:
  • overall survival [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • number of complete or partial responses [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
    according to Common Toxicity Criteria for Adverse Events v. 4.03

  • number of patients taking oral antidiabetic therapy [ Time Frame: at baseline ] [ Designated as safety issue: No ]
  • number of patients taking antithrombotic therapy [ Time Frame: at baseline ] [ Designated as safety issue: No ]
  • progression free survival [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    as measured by independent central review


Other Outcome Measures:
  • predictive clinical factors for efficacy of bevacizumab [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • correlation of baseline plasma biomarker expression and clinical outcome [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 400
Study Start Date: November 2013
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: Paclitaxel Drug: Carboplatin Drug: pegylated liposomal doxorubicin
Other Name: Caelyx
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.

Drug: Bevacizumab
Other Name: Avastin
Drug: Paclitaxel Drug: Carboplatin Drug: pegylated liposomal doxorubicin
Other Name: Caelyx
Drug: Gemcitabine

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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.
  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: NCT01802749

Contacts
Contact: Francesco Perrone, M.D., Ph.D. +39 081 5903571 francesco.perrone@usc-intnapoli.net
Contact: Sandro Pignata, M.D. +39 081 5903383 s.pignata@istitutotumori.na.it

Locations
France
Centre Hospitalier Intercommunal de Créteil Recruiting
Créteil, France
Italy
Centro di Riferimento Oncologico Recruiting
Aviano, Italy
A.O. G. Rummo Recruiting
Benevento, Italy
Ospedale Senatore Antonio Perrino Recruiting
Brindisi, Italy
Istituto Romagnolo per lo Studio e la Cura dei Tumori Recruiting
Meldola, Italy
Istituto Nazionale Tumori Recruiting
Milano, Italy
Istituto Nazionale dei Tumori , Oncologia Medica - Dipartimento Uro-Ginecologico Recruiting
Napoli, Italy
Osp Silvestrini Recruiting
Perugia, Italy
Switzerland
IOSI Recruiting
Bellinzona, Switzerland
Sponsors and Collaborators
National Cancer Institute, Naples
Mario Negri Institute for Pharmacological Research
Investigators
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. Second University of Naples
Principal Investigator: Irene Floriani, Ph.D. Mario Negri Institute
  More Information

No publications provided

Responsible Party: National Cancer Institute, Naples
ClinicalTrials.gov Identifier: NCT01802749     History of Changes
Other Study ID Numbers: MITO-16 -MANGO-OV2b, 2012-004362-17, ENGOT-ov 17
Study First Received: February 27, 2013
Last Updated: April 10, 2014
Health Authority: Italy: Ethics Committee

Keywords provided by National Cancer Institute, Naples:
second line
platinum sensitive
first line bevacizumab
biologic factors
clinical factors

Additional relevant MeSH terms:
Ovarian Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Doxorubicin
Gemcitabine
Bevacizumab
Carboplatin
Paclitaxel
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on July 29, 2014