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

September 5, 2023 updated by: ARCAGY/ GINECO GROUP

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

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

188

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Angers, France
        • Centre Paul Papin
      • Avignon, France
        • Institut Ste Catherine
      • Bordeaux, France
        • Institut Bergonie
      • Bordeaux, France
        • Clinique Tivoli
      • Bordeaux, France
        • Polyclinique Bordeaux Nord
      • Caen, France
        • Centre Francois Baclesse
      • Clermont-Ferrand, France
        • Centre Jean Perrin
      • Contamine-sur-Arve, France
        • Centre Hospitalier Alpes Leman
      • Créteil, France
        • Centre Hospitalier Intercommunal de Créteil
      • Dax, France
        • Centre Hospitalier de Dax
      • Dijon, France
        • Centre Georges François Leclerc
      • Lille, France
        • Centre Oscar Lambret
      • Lille, France
        • Centre Hospitalier Régional Universitaire de Lille - Hôpital Huriez
      • Limoges, France
        • Centre Hospitalier Universitaire Dupuytren
      • Lyon, France
        • Centre Leon Berard
      • Montpellier, France
        • ICM Val d'Aurelle
      • Nantes, France
        • Hôpital Privé du Confluent S.A.S.
      • Nantes, France
        • Centre Catherine de Sienne
      • Nice, France
        • Centre Antoine Lacassagne
      • Orléans, France
        • Centre Hospitalier Regional
      • Paris, France
        • Hôpital Cochin
      • Paris, France
        • Hôpital Européen Georges Pompidou
      • Paris, France
        • Hopital Tenon
      • Paris, France
        • Institut Mutualiste Montsouris-Jourdan
      • Pierre-Bénite, France
        • Centre Hospitalier Lyon-Sud
      • Poitiers, France
        • Milétrie - Centre Hospitalier Universitaire de Poitiers
      • Reims, France
        • Institut Jean Godinot
      • Rouen, France
        • Centre Henri Becquerel
      • Saint Brieuc, France
        • Clinique Armoricaine de Radiologie
      • Saint-Cloud, France
        • Hopital René Huguenin
      • St Herblain, France
        • Ico Rene Gauducheau
      • Strasbourg, France
        • Hôpital Civil
      • Thonon-les-Bains, France
        • Hopitaux du Leman
      • Toulouse, France
        • Centre Claudius Regaud
      • Vandoeuvre-Les-Nancy, France
        • Institut de Cancérologie de Lorraine
      • Villejuif, France
        • Gustave Roussy

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Median Progression-free Survival (PFS) in each study arm
Time Frame: average of 18 months
average of 18 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Response rate
Time Frame: 2 months after beginning of treatment
2 months after beginning of treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

ARCAGY/ GINECO GROUP

Investigators

  • Principal Investigator: Gwénaël Ferron, MD, Institut Claudius Regaud

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2012

Primary Completion (Actual)

May 1, 2015

Study Completion (Actual)

March 1, 2016

Study Registration Dates

First Submitted

April 19, 2012

First Submitted That Met QC Criteria

April 23, 2012

First Posted (Estimated)

April 24, 2012

Study Record Updates

Last Update Posted (Actual)

September 6, 2023

Last Update Submitted That Met QC Criteria

September 5, 2023

Last Verified

September 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GINECO-OV119

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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