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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01583322
Recruitment Status : Completed
First Posted : April 24, 2012
Last Update Posted : March 17, 2016
Sponsor:
Information provided by (Responsible Party):
ARCAGY/ GINECO GROUP

Tracking Information
First Submitted Date  ICMJE April 19, 2012
First Posted Date  ICMJE April 24, 2012
Last Update Posted Date March 17, 2016
Study Start Date  ICMJE June 2012
Actual Primary Completion Date May 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 23, 2012)
Median Progression-free Survival (PFS) in each study arm [ Time Frame: average of 18 months ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 23, 2012)
Response rate [ Time Frame: 2 months after beginning of treatment ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Vargatef in Addition to First Line Chemotherapy With Interval Debulking Surgery in Patients With Ovarian Cancer
Official Title  ICMJE 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
Brief Summary

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).

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Ovarian Cancer
Intervention  ICMJE
  • 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.

  • 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.

Study Arms  ICMJE
  • Experimental: vargatef/Nintedanib
    Intervention: Drug: vargatef
  • Placebo Comparator: placebo
    Intervention: Drug: placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 23, 2012)
188
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE March 2016
Actual Primary Completion Date May 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01583322
Other Study ID Numbers  ICMJE GINECO-OV119
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party ARCAGY/ GINECO GROUP
Study Sponsor  ICMJE ARCAGY/ GINECO GROUP
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Gwénaël Ferron, MD Institut Claudius Régaud
PRS Account ARCAGY/ GINECO GROUP
Verification Date March 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP