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Neoadjuvant Therapy in Advanced Ovarian Cancer With Avastin (NOVA)

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ClinicalTrials.gov Identifier: NCT01847677
Recruitment Status : Active, not recruiting
First Posted : May 7, 2013
Last Update Posted : August 20, 2018
Sponsor:
Collaborator:
Roche Pharma AG
Information provided by (Responsible Party):
Grupo Español de Investigación en Cáncer de Ovario

Brief Summary:
Recently results have shown that Bevacizumab is active both in monotherapy and in combination therapy in patients with ovarian cancer. One of our objectives is to evaluate whether the addition of neoadjuvant bevacizumab improves the response and whether this affects the evolution of patients.

Condition or disease Intervention/treatment Phase
Cancer, Ovarian Drug: Bevacizumab Drug: Paclitaxel Drug: Carboplatin Phase 2

Detailed Description:

Epithelial ovarian cancer (OC) is the fourth leading cause of cancer death in women, after lung, breast and colon cancer, and it represents the most common cause of death from gynaecological malignancies. The high mortality associated with OC is due to the lack of screening tests that enable an early diagnosis, thus the majority of patients are diagnosed at advanced stages of the disease when the chances of a cure are very limited. In fact, the 5-year overall survival (OS) rate for stage III-IV OC does not exceed 20-30% in many series. The standard treatment for advanced OC is maximal cytoreductive surgery (or debulking) followed by the administration of 6 cycles of adjuvant chemotherapy with carboplatin and paclitaxel.

In recent years, a number of studies have been carried out with antiangiogenic drugs. Specifically, bevacizumab, an anti-VEGF monoclonal antibody, has been shown to be active both in monotherapy and combination therapy in patients with OC that have received multiple previous lines of chemotherapy.

One of the objectives is to evaluate whether the addition of neoadjuvant bevacizumab improves the response and whether this affects the evolution of patients.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 71 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized Phase II Multi-centric Open Label Clinical Trial to Determine the Efficacy and Toxicity of Preoperative Chemotherapy With or Without Bevacizumab in Patients With Advanced Ovarian Cancer
Actual Study Start Date : May 6, 2013
Actual Primary Completion Date : June 4, 2015
Estimated Study Completion Date : December 2018


Arm Intervention/treatment
Active Comparator: Paclitaxel & Carboplatin
  1. Preoperative treatment Cycle 1 to 4 (4 cycles every 3 weeks of chemotherapy pre-surgery)

    • Carboplatin AUC 6 i.v. first day
    • Paclitaxel 175 mg/m2 i.v. first day
  2. Surgery
  3. Post-Operative treatment

Cycle 5 to 7 (3 cycles every 3 weeks of chemotherapy post-surgery):

  • Carboplatin AUC 6 i.v. first day
  • Paclitaxel 175 mg/m2 i.v. first day
  • Bevacizumab 15 mg/Kg i.v. first day1

When the chemotherapy treatment is completed, the patient will continue with maintenance bevacizumab until 15 months length treatment.

Drug: Paclitaxel
Other Name: Taxol

Drug: Carboplatin
Other Name: Paraplatin

Experimental: Paclitaxel & Carboplatin & Bevacizumab

4 cycles every 3 weeks (at least 3 Bevacizumab neoadjuvant cycles): Carboplatin AUC 6 i.v. first day Paclitaxel 175 mg/m2 i.v. first day Bevacizumab 15 mg/Kg i.v. first day.

b) Surgery Ovarian cancer surgery should be performed according to FIGO guidelines.

c) Postoperative treatment

Both arms:

Cycle 5 to 7 (3 cycles every 3 weeks of chemotherapy post-surgery):

Carboplatin AUC 6 i.v. first day Paclitaxel 175 mg/m2 i.v. first day Bevacizumab 15 mg/Kg i.v. first day.

When the chemotherapy treatment is completed, the patient will continue with maintenance bevacizumab until 15 months length treatment.

Drug: Bevacizumab
Other Name: Avastin

Drug: Paclitaxel
Other Name: Taxol

Drug: Carboplatin
Other Name: Paraplatin




Primary Outcome Measures :
  1. Complete response rate [ Time Frame: average 24 months ]
    Complete response rate (microscopic residual tumor included) assessed by the surgeon at laparotomy after neoadjuvant therapy.


Secondary Outcome Measures :
  1. Safety: toxicities and surgical complications [ Time Frame: average 24 months ]
    Safety and tolerability of the treatment will be assessed by adverse event description: incidence, severity, time of onset, causes, and abnormal laboratory values .

  2. Surgical feasibility [ Time Frame: average 24 months ]
    rate of patients in which surgery is feasible, comparing both arms.

  3. Optimal surgery rate [ Time Frame: average 24 months ]
    rate of patients in which surgery is optimal (residual disease<1cm), comparing both arms

  4. RECIST 1.1 responses and correlation with serological responses (GCIG criteria) [ Time Frame: average 24 months ]
    It will be assesed using descriptive statistics techniques such as frequency tables and contingency tables

  5. Progression-free survival according RECIST 1.1 criteria [ Time Frame: average 24 months ]
    tables of survival will be constructed by the Kaplan-Meier method. Mean and median, both with confidence intervals of 95%. Comparisons between groups will be made by log-rank test.

  6. Overall Survival (OS) [ Time Frame: average 24 months ]
    tables of survival will be constructed by the Kaplan-Meier method. Mean and median, both with confidence intervals of 95%. Comparisons between groups will be made by log-rank test.

  7. Association between clinical response and the expression of protein biomarkers, in pre-and post-surgical plasma. [ Time Frame: average 24 months ]
    It will be assesed using descriptive statistics techniques such as frequency tables and contingency tables

  8. Biomarkers: Epithelial-mesenchymal transition performed at C.S. Parc Taulí [ Time Frame: average 24 months ]
    It will be assesed using descriptive statistics techniques such as frequency tables and contingency tables


Other Outcome Measures:
  1. Histological response: comparison between the obtained response only with chemotherapy or chemotherapy and bevacizumab. [ Time Frame: average 24 months ]
    information correlating the clinical laboratory with the response to treatment.

  2. Association of clinical response with other potential biomarkers, including but not limited to, single nucleotide polymorphisms (SNP) and specific tumor markers. [ Time Frame: Average 24 months ]
    It will be assesed using descriptive statistics techniques such as frequency tables and contingency tables



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Women over 18 years old
  2. Obtained informed consent, in writing and signed
  3. Histological confirmation of primary peritoneal carcinoma or fallopian tube carcinoma
  4. Planned interval debulking surgery
  5. ECOG:0 to 2
  6. Life expectancy >12 weeks

Exclusion Criteria:

  1. Non-epithelial ovarian cancer, including malignant mixed Müllerian tumors.
  2. Borderline ovarian tumors.
  3. Administration of intraperitoneal chemotherapy planned.
  4. Previous systemic anti-tumor treatment against ovarian cancer.
  5. Intestinal obstruction or sub-occlusion, intestinal infiltration shown by CT scan or rectosigmoid infiltration in gynaecological examination.
  6. Uncontrolled hypertension.
  7. Any previous radiotherapy: abdomen or pelvis.
  8. Major traumatic injuries in the 4 weeks prior to the first potential dose of bevacizumab.
  9. History or clinical suspicion of brain metastases or spinal cord compression.
  10. History or evidence of central nervous system (CNS) disorders, unless properly treated with standard medical treatment.
  11. Cerebrovascular accident (CVA), transient ischemic attack (TIA) or subarachnoid haemorrhage (SAH) in the 6 months prior to randomization.
  12. Fertile women of childbearing age who are not willing to use effective contraception during the study and at least 6 months after the study.
  13. Women that are breastfeeding or pregnant.
  14. Prior exposure to mouse CA-125 antibody.
  15. Treatment with any other experimental product, or participation in another clinical trial within 30 days prior to inclusion.
  16. Malignant tumors other than ovarian cancer within the 5 years prior to randomisation, with the exception of cervical carcinoma in situ treated correctly and/or basal-cell carcinoma.
  17. Known hypersensitivity to bevacizumab or any of its excipients (including Cremophor).
  18. Non-healing wound, active peptic ulcer or bone fracture. Patients with healing incised granulomas by secondary intention, with no evidence of fascial dehiscence or infection can be included, but they require three weeks of wound control.
  19. History or evidence of bleeding or thrombotic diathesis
  20. Current or recent continued use of aspirin > 325 mg / day (within 10 days prior to randomization)
  21. Current or recent use (within 10 days before the first cycle of treatment) of full doses of anticoagulants or thrombolytics administered orally or parenterally for therapeutic purposes (except for vascular permeability, in which case the INR should be kept below 1.5).
  22. Clinically significant cardiovascular disease, including:

    • Myocardial infarction or unstable angina (≤ 6 months before randomization)
    • Congestive heart failure (CHF) class ≥ II of the NYHA (New York Heart Association)
    • Poorly controlled cardiac arrhythmia despite medication (may include patients with atrial fibrillation with controlled frequency)
    • Peripheral vascular disease ≥ grade 3 (i.e. symptomatic and interfering with activities or daily living [ADL] needing repair or review)
  23. Pre-existing sensory or motor neuropathy, ≥ grade 2
  24. Demonstration of any other neurological or metabolic dysfunction involving a reasonable suspicion of the existence of a disease or condition that contraindicates the use of an experimental drug, or that involves an increased risk to the patient of treatment-related complications
  25. No medical or psychiatric illness that may impede the performance of a systemic or surgical treatment
  26. Laboratory:

Inadequate bone marrow function:

  • ANC: <1.5 x 109/l
  • platelet count <100 x 109/l
  • Hb <9 g/dl. (Patients may be transfused)

Inadequate coagulation parameters: Activated partial thromboplastin time (APTT) >1.5 x ULN or INR >1.5

Inadequate liver function, defined as:

  • Serum (total) bilirubin >1.5 x the upper limit of normal (ULN) for the institution
  • AST & ALT > 2.5 x ULN (> 5 x ULN in patients with liver metastases) or alkaline phosphatase > 2.5 x ULN (or > 5 x ULN in case of liver metastases or > 10 x ULN in case of bone metastases).

Inadequate renal function, defined as:

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

Information from the National Library of Medicine

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): NCT01847677


Locations
Spain
Hospital La Fe
Valencia, Comunidad Valenciana, Spain, 46026
Hospital Germans Trias i Pujol
Badalona, Spain
Hospital Clínic
Barcelona, Spain
Hospital Sant Pau
Barcelona, Spain
H. Reina Sofia
Cordoba, Spain
ICO Girona
Girona, Spain
ICO Hospitalet
Hospitalet del Llobregat, Spain
Hospital 12 de Octubre
Madrid, Spain
Hospital Clínico San Carlos
Madrid, Spain
Hospital Universitario Morales Meseguer
Murcia, Spain
Hospital Son Llatzer
Palma Mallorca, Spain
Parc Taulí
Sabadell, Spain
Hospital Marqués de Valdecilla
Santander, Spain
Sponsors and Collaborators
Grupo Español de Investigación en Cáncer de Ovario
Roche Pharma AG
Investigators
Study Chair: Yolanda García, MD C.S Parc Taulí

Responsible Party: Grupo Español de Investigación en Cáncer de Ovario
ClinicalTrials.gov Identifier: NCT01847677     History of Changes
Other Study ID Numbers: GEICO-1205
2012-003883-31 ( EudraCT Number )
First Posted: May 7, 2013    Key Record Dates
Last Update Posted: August 20, 2018
Last Verified: August 2018

Keywords provided by Grupo Español de Investigación en Cáncer de Ovario:
ovarian cancer
neoadyuvant
bevacizumab

Additional relevant MeSH terms:
Ovarian Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Bevacizumab
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Endocrine System Diseases
Gonadal Disorders
Paclitaxel
Albumin-Bound Paclitaxel
Carboplatin
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors