Vargatef in Addition to First Line Chemotherapy With Interval Debulking Surgery in Patients With Ovarian Cancer (CHIVA)

This study is currently recruiting participants.
Verified January 2014 by ARCAGY/ GINECO GROUP
Sponsor:
Information provided by (Responsible Party):
ARCAGY/ GINECO GROUP
ClinicalTrials.gov Identifier:
NCT01583322
First received: April 19, 2012
Last updated: January 9, 2014
Last verified: January 2014
  Purpose

Patients with extensive and bulky disease are often those whose initial surgery is delayed after 3 or 4 cycles of neo-adjuvant chemotherapy.

In that case, there is, indeed, some concern to administer bevacizumab during the chemotherapy surrounding the interval debulking surgery due to the long half life (14- 21 days) of this monoclonal antibody and the interference of anti angiogenic agents with wound healing.

Vargatef® (Nintedanib) might offer a better alternative to bevacizumab in the neo-adjuvant setting. Vargatef® (Nintedanib) has a much shorter half-life of 7 to 19 hours. Preliminary experience in cancer did not show a trend for increased incidence of fistula or bowel perforation. For more details please refer to the investigator drug brochure for Vargatef® (Nintedanib).

This trial will compare progression-free survival and surgical complications of 188 patients with FIGO stage IIIC/IV treated in first line with either neo-adjuvant chemotherapy (carboplatin & paclitaxel) and interval debulking surgery or the same treatment + Vargatef® (Nintedanib).


Condition Intervention Phase
Ovarian Cancer
Drug: vargatef
Drug: placebo
Phase 2

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

Resource links provided by NLM:


Further study details as provided by ARCAGY/ GINECO GROUP:

Primary Outcome Measures:
  • Median Progression-free Survival (PFS) in each study arm [ Time Frame: average of 18 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Response rate [ Time Frame: 2 months after beginning of treatment ] [ Designated as safety issue: No ]

Estimated Enrollment: 188
Study Start Date: June 2012
Estimated Study Completion Date: December 2018
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: vargatef/Nintedanib Drug: vargatef

400 mg (200 mg twice daily) Route of administration= oral Twice daily (to be swallowed unchewed with a glass of water of about 250 mL. If taken twice the dose interval should be of around 12 hours at the same times every day, usually in the morning and the evening after food intake).

Continuous daily dosing until progression of disease or until criteria for interruption of treatment are met, no intake of Vargatef® (Nintedanib) on days of paclitaxel and carboplatin administration. The maximum time on monotherapy is 2 years.

Placebo Comparator: placebo Drug: placebo

Contains 0 mg of Vargatef® (Nintedanib) in capsules matching 100 mg and 150 mg of Vargatef® (Nintedanib) Route of administration: oral Twice daily (to be swallowed unchewed with a glass of water of about 250 mL. If taken twice the dose interval should be of around 12 hours at the same times every day, usually in the morning and the evening after food intake).

Continuous daily dosing until progression of disease or until criteria for interruption of treatment is met, no intake of placebo on days of paclitaxel and carboplatin administration.

The maximum time on monotherapy is 2 years.


  Eligibility

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

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 mL/min,

  • 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 infection,
  • Poorly controlled diabetes mellitus or other contraindication to high dose corticosteroid therapy,
  • Clinical symptoms of brain metastases and/or diagnosis of brain metastases on imaging,
  • 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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01583322

Contacts
Contact: Frédéric Marmion, Msc 01 42 34 83 23 fmarmion@arcagy.org

Locations
France
Centre Paul Papin Recruiting
Angers, France
Institut Ste Catherine Recruiting
Avignon, France
Institut Bergonié Recruiting
Bordeaux, France
Clinique Tivoli Recruiting
Bordeaux, France
Polyclinique Bordeaux Nord Recruiting
Bordeaux, France
centre Francois baclesse Recruiting
Caen, France
Centre Georges François leclerc Recruiting
Dijon, France
Centre Oscar Lambret Recruiting
Lille, France
BACHELOT Recruiting
Lyon, France, 69000
Contact: Thomas BACHELOT, Md    + 33 4 78 78 26 54    bachelot@lyon.fnclcc.fr   
Centre Léon bérard Recruiting
Lyon, France
Centre Alexis Vautrin Recruiting
Nancy, France
Centre Catherine de Sienne Recruiting
Nantes, France
Centre Hospitalier Régional Recruiting
Orléans, France
Recruiting
Paris, France
Contact: Jérôme ALEXANDRE, PhD         
Principal Investigator: Jérôme ALEXANDRE, PhD         
Centre Hospitalier Lyon-sud Recruiting
Pierre-Bénite, France, 69495
Contact: Gilles Freyer, MD, PhD    + 33 (0) 478863324      
Principal Investigator: Gilles Freyer, MD, PhD         
Institut Jean Godinot Recruiting
Reims, France
Centre Henri Becquerel Recruiting
Rouen, France
Clinique Armoricaine de Radiologie Recruiting
Saint Brieuc, France
ICO René Gauducheau Recruiting
St Herblain, France
Hôpital Civil Recruiting
Strasbourg, France
Centre Claudius Régaud Recruiting
Toulouse, France, 31052
Contact: Laurence GLADIEFF, physician    05 61 42 41 19      
Principal Investigator: Laurence GLADIEFF, physician         
Sponsors and Collaborators
ARCAGY/ GINECO GROUP
Investigators
Principal Investigator: Gwénaël Ferron, MD Institut Claudius Régaud
  More Information

No publications provided

Responsible Party: ARCAGY/ GINECO GROUP
ClinicalTrials.gov Identifier: NCT01583322     History of Changes
Other Study ID Numbers: GINECO-OV119
Study First Received: April 19, 2012
Last Updated: January 9, 2014
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by ARCAGY/ GINECO GROUP:
ovarian cancer
debulking surgery
interval debulking
vargatef
nintedanib
maintenance
first line
paclitaxel
carboplatin

Additional relevant MeSH terms:
Adenocarcinoma
Ovarian Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Carboplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 16, 2014