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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

Phase 2
18 Years
Open (Enrolling)
Cancer, Ovarian

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Trial Information

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

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.

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

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

17. Known hypersensitivity to bevacizumab or any of its excipients (including

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

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

- 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

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Complete response rate

Outcome Description:

Complete response rate (microscopic residual tumor included) assessed by the surgeon at laparotomy after neoadjuvant therapy.

Outcome Time Frame:

average 24 months

Safety Issue:


Principal Investigator

Yolanda García, MD

Investigator Role:

Study Chair

Investigator Affiliation:

C.S Parc Taulí


Spain: Spanish Agency of Medicines

Study ID:




Start Date:

April 2013

Completion Date:

June 2016

Related Keywords:

  • Cancer, Ovarian
  • ovarian cancer
  • neoadyuvant
  • bevacizumab
  • Ovarian Neoplasms