Neoadjuvant Therapy in Advanced Ovarian Cancer With Avastin

Cancer, Ovarian Clinical Trial

— NOVA  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01847677
• Other study ID #: GEICO-1205
• Secondary ID: 2012-003883-31
• Status: Terminated
• Phase: Phase 2
• Start date: May 6, 2013
• Est. completion date: May 17, 2019

Study information

• Verified date: May 2019
• Source: Grupo Español de Investigación en Cáncer de Ovario
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 71
• Est. completion date: May 17, 2019
• Est. primary completion date: June 4, 2015
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cancer, Ovarian
• Carcinoma, Ovarian Epithelial
• Ovarian Neoplasms

Intervention

Drug:
• Bevacizumab

• Paclitaxel

• Carboplatin

Locations

Country	Name	City	State
Spain	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	Hospital La Fe	Valencia	Comunidad Valenciana

Sponsors (2)

Lead Sponsor	Collaborator
Grupo Español de Investigación en Cáncer de Ovario	Roche Pharma AG

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Histological response: comparison between the obtained response only with chemotherapy or chemotherapy and bevacizumab.	information correlating the clinical laboratory with the response to treatment.	average 24 months
Other	Association of clinical response with other potential biomarkers, including but not limited to, single nucleotide polymorphisms (SNP) and specific tumor markers.	It will be assesed using descriptive statistics techniques such as frequency tables and contingency tables	Average 24 months
Primary	Complete response rate	Complete response rate (microscopic residual tumor included) assessed by the surgeon at laparotomy after neoadjuvant therapy.	average 24 months
Secondary	Safety: toxicities and surgical complications	Safety and tolerability of the treatment will be assessed by adverse event description: incidence, severity, time of onset, causes, and abnormal laboratory values .	average 24 months
Secondary	Surgical feasibility	rate of patients in which surgery is feasible, comparing both arms.	average 24 months
Secondary	Optimal surgery rate	rate of patients in which surgery is optimal (residual disease<1cm), comparing both arms	average 24 months
Secondary	RECIST 1.1 responses and correlation with serological responses (GCIG criteria)	It will be assesed using descriptive statistics techniques such as frequency tables and contingency tables	average 24 months
Secondary	Progression-free survival according RECIST 1.1 criteria	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.	average 24 months
Secondary	Overall Survival (OS)	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.	average 24 months
Secondary	Association between clinical response and the expression of protein biomarkers, in pre-and post-surgical plasma.	It will be assesed using descriptive statistics techniques such as frequency tables and contingency tables	average 24 months
Secondary	Biomarkers: Epithelial-mesenchymal transition performed at C.S. Parc Taulí	It will be assesed using descriptive statistics techniques such as frequency tables and contingency tables	average 24 months