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Randomized Double Blind Placebo-controlled Phase II Trial of Vargatef® (Nintedanib) in Addition to First Line Chemotherapy With Interval Debulking Surgery in Patients With Adenocarcinoma of the Ovary, the Fallopian Tube or Serous Adenocarcinoma of the Peritoneum

Phase 2
18 Years
Open (Enrolling)
Ovarian Cancer

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Trial Information

Randomized Double Blind Placebo-controlled Phase II Trial of Vargatef® (Nintedanib) in Addition to First Line Chemotherapy With Interval Debulking Surgery in Patients With Adenocarcinoma of the Ovary, the Fallopian Tube or Serous Adenocarcinoma of the Peritoneum

Inclusion Criteria:

- First diagnosis of histological confirmed (cytology alone excluded) epithelial
ovarian cancer, fallopian tube or primary peritoneal cancer. Histology should be
obtained by laparoscopy (or by laparotomy),

- FIGO-Stages IIIC - IV,

- ECOG performance status < 2,

- Life expectancy of at least 6 months,

- Primary debulking surgery denied and maximum surgical effort of cytoreduction with
the goal of no residual disease planned as interval debulking surgery,

- Interval between diagnosis and enrolment (informed consent) ≤ 8 weeks,

- Adequate hepatic, renal and bone marrow functions:

Platelets > 100 000 /μL, Hemoglobin > 9.0 g/dL, Absolute Neutrophil Count (ANC) > 1500/μL,
Prothrombin time and/or partial thromboplastin time < 50% deviation from normal limits in
the absence of therapeutic anticoagulation, Proteinuria < CTCAE grade 2, Total bilirubin ≤
upper limit of normal (ULN), ALT and/or AST ≤ 2.5 x ULN, Glomerular filtration rate >40

- Females, age 18 years or older,

- Patient has given written informed consent,

Exclusion Criteria:

- Histological diagnosis of malignant tumour of non-epithelial origin (e.g. germ cell
tumour, malignant mixed mullerian tumour, sex cord-stromal tumour) of the ovary, the
fallopian tube or peritoneum or borderline tumour of the ovary (tumour of low
malignant potential),

- Non-healing wound, ulcer (intestinal tract, skin) or bone fracture,

- Clinical symptoms or signs of gastrointestinal obstruction,

- History of major thromboembolic event, defined as:

- Pulmonary embolism (PE) within 6 months prior to enrolment,

- Recurrent pulmonary embolism (history of at least 2 events),

- History of at least 2 unprovoked (without a transient or reversible risk factor)
events of proximal deep venous thrombosis,

- Prior thrombosis or thromboembolic event in the presence of an inherited coagulopathy
(including deficiency of antithrombin, deficiency of protein C or protein S, Factor V
Leiden mutation, Prothrombin G20210A mutation),

- Patients with perioperative thrombosis including proximal deep vein thrombosis (DVT)
or thrombosis of visceral vessels not associated with pulmonary embolism may be
included in the trial if stable therapeutic anticoagulation is documented,

- Known inherited or acquired bleeding disorder,

- Significant cardiovascular diseases, including:

- Hypertension not controlled by medical therapy,

- Unstable angina within the past 6 months,

- History of myocardial infarction within the past 6 months,

- Congestive heart failure > NYHA II,

- Clinically relevant cardiac arrhythmia

- Peripheral vascular disease Fontaine stage ≥3,

- Clinically relevant pericardial effusion (e.g. pericardial effusion with
echocardiographic or clinical signs of haemodynamic impairment),

- History of a cerebral vascular accident, transient ischemic attack or subarachnoid
hemorrhage within the past 6 months,

- Serious infections in particular if requiring systemic antibiotic (antimicrobial,
antifungal) or antiviral therapy, including HIV-infection, hepatitis B and/or C

- Poorly controlled diabetes mellitus or other contraindication to high dose
corticosteroid therapy,

- Clinical symptoms of brain metastases and/or diagnosis of brain metastases on

- Pre-existing sensory or motor neuropathy CTCAE ≥ 2, except due to trauma,

- Gastrointestinal disorders or abnormalities that would interfere with absorption of
the study drug,

- Other malignancy diagnosed within the past 5 years, except:

- non-melanomatous skin cancer (if adequately treated),

- cervical carcinoma in situ (if adequately treated),

- carcinoma in situ of the breast (if adequately treated),

- prior or synchronous endometrial cancer (if adequately treated), provided the
following criteria are met:

- Disease stage FIGO ≤ IB,

- No more than superficial myometrial invasion,

- Not poorly differentiated (less than grade 3, no papillary serous or clear
cell histology),

- Prior systemic therapy for ovarian cancer (e.g. chemotherapy, monoclonal antibody
therapy, oral targeted therapy, hormonal therapy),

- Prior radiotherapy to the abdomen or prior radiotherapy to an extra-abdominal target
volume that would bear the risk of increased toxicity of chemotherapy,

- Hypersensitivity to Vargatef® (Nintedanib) and/or the excipients of the trial drugs,

- Serious illness or concomitant non-oncological disease such as neurologic,
psychiatric or infectious disease, active ulcers (gastrointestinal tract, skin) or a
laboratory abnormality that may increase the risk associated with study participation
or study drug administration and in the judgment of the investigator would make the
patient inappropriate for entry into the study,

- Patients with preserved reproductive capacity who are sexually active and unwilling
to use a medically acceptable method of contraception (e.g. such as implants,
injectables, combined oral contraceptives, some intrauterine devices or vasectomized
partner) during the trial and for at least twelve months after end of active therapy,

- Pregnancy or breast feeding,

- Psychological, familial, sociological or geographical factors potentially hampering
compliance with the study protocol and follow-up schedule,

- Active alcohol or drug abuse,

- Any contraindications for therapy with paclitaxel or carboplatin, e.g. a history of
severe hypersensitivity reactions to paclitaxel or platinum-containing compounds and
their excipients, or other drugs formulated with Polyoxyl 35 Castor Oil - ELP,

- Treatment with other investigational drugs or participation in another clinical trial
testing a drug within the past four weeks before start of therapy or concomitantly
with this trial.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Outcome Measure:

Median Progression-free Survival (PFS) in each study arm

Outcome Time Frame:

average of 18 months

Safety Issue:


Principal Investigator

Gwénaël Ferron, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Institut Claudius Régaud


France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Study ID:




Start Date:

June 2012

Completion Date:

December 2018

Related Keywords:

  • Ovarian Cancer
  • ovarian cancer
  • debulking surgery
  • interval debulking
  • vargatef
  • nintedanib
  • maintenance
  • first line
  • paclitaxel
  • carboplatin
  • Adenocarcinoma
  • Ovarian Neoplasms