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Ovarian CancerPhase 2CHIVANCT01583322

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

A Phase 2 study testing vargatef in people with Ovarian Cancer, run by ARCAGY/ GINECO GROUP at 36 sites in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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)… Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Ovarian Cancer
What is being tested?
vargatef
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
188 participants
Where
36 sitesFrance
Study dates
Jun 2012to Mar 2016
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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,
Show all 10Show fewer
  • 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,

Who cannot join

  • 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),
Show all 42Show fewer
  • 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.

Trial locations and contacts

36 sites in 1 country.

36 sites in 1 country

France36 sites

  • Centre Paul Papin

    Angers

  • Institut Ste Catherine

    Avignon

  • Clinique Tivoli

    Bordeaux

  • Institut Bergonié

    Bordeaux

  • Polyclinique Bordeaux Nord

    Bordeaux

  • Centre François Baclesse

    Caen

  • Centre Jean Perrin

    Clermont-Ferrand

  • Centre Hospitalier Alpes Leman

    Contamine-sur-Arve

  • Centre Hospitalier Intercommunal de Créteil

    Créteil

  • Centre Hospitalier de Dax

    Dax

  • Centre Georges François Leclerc

    Dijon

  • Centre Hospitalier Régional Universitaire de Lille - Hôpital Huriez

    Lille

  • Centre Oscar Lambret

    Lille

  • Centre Hospitalier Universitaire Dupuytren

    Limoges

  • Centre Léon bérard

    Lyon

  • ICM Val d'Aurelle

    Montpellier

  • Centre Catherine de Sienne

    Nantes

  • Hôpital Privé du Confluent S.A.S.

    Nantes

  • Centre Antoine Lacassagne

    Nice

  • Centre Hospitalier Régional

    Orléans

  • Hôpital Cochin

    Paris

  • Hôpital Européen Georges Pompidou

    Paris

  • Hôpital Tenon

    Paris

  • Institut Mutualiste Montsouris-Jourdan

    Paris

  • Centre Hospitalier Lyon-sud

    Pierre-Bénite

  • Milétrie - Centre Hospitalier Universitaire de Poitiers

    Poitiers

  • Institut Jean Godinot

    Reims

  • Centre Henri Becquerel

    Rouen

  • Clinique Armoricaine de Radiologie

    Saint-Brieuc

  • Hôpital René Huguenin

    Saint-Cloud

  • ICO René Gauducheau

    Saint-Herblain

  • Hôpital Civil

    Strasbourg

  • Hôpitaux Du Leman

    Thonon-les-Bains

  • Centre Claudius Régaud

    Toulouse

  • Institut de Cancérologie de Lorraine

    Vandœuvre-lès-Nancy

  • Gustave Roussy

    Villejuif

Other trials in France

About this study

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

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.

Read more

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).

Conditions
Ovarian Cancer
Being tested
vargatef, placebo
Keywords
ovarian cancer, debulking surgery, interval debulking, vargatef, nintedanib, maintenance, first line, paclitaxel, carboplatin
Medical subject headings
Ovarian Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • vargatefDrug

    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.

  • placeboDrug

    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 groups in NCT01583322
Study groupRoleWhat they receive
vargatef/NintedanibExperimentalNot described
Receives: Drug: vargatef
placeboPlacebo comparatorNot described
Receives: Drug: placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Measured: average of 18 months

Secondary outcomes (1)

  1. Response rate

    Measured: 2 months after beginning of treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Apr 2012 (estimated)
  2. Study startJun 2012
  3. Primary completionMay 2015
  4. Study completionMar 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
188 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01583322
Sponsor's protocol ID
GINECO-OV119
Acronym
CHIVA
Status last verified
Sep 2023
First submitted
19 Apr 2012
Last updated
6 Sep 2023
Results posted
No
Data monitoring committee
Yes

Publications

  • Marchetti C, Ferron G, Colomban O, Giannarelli D, Blanc-Durand F, Scambia G, Just PA, Lorusso D, Pujade-Lauraine E, Ergasti R, Lortholary A, Sassu CM, Ray-Coquard I, Capomacchia FM, Combe P, Apostol AI, Zannoni GF, Carrot A, Malapelle U, Leary A, Fagotti A, You B. Predictors of Successful Neoadjuvant Chemotherapy and Interval Cytoreductive Surgery in Management of Ovarian Cancer. JCO Oncol Pract. 2025 Nov 24:OP2500469. doi: 10.1200/OP-25-00469. Online ahead of print.

    PubMed 41284952

  • Azais H, Brochard C, Taly V, Benoit L, Ferron G, Ray-Coquard I, You B, Abadie-Lacourtoisie S, Lebreton C, Venat L, Louvet C, Favier L, Blonz C, Dohollou N, Malaurie E, Dubot C, Kurtz JE, Pujade-Lauraine E, Rouleau E, Leary A, Bats AS, Blons H, Laurent-Puig P. Prognostic value of circulating tumor DNA at diagnosis and its early decrease after one cycle of neoadjuvant chemotherapy for patients with advanced epithelial ovarian cancer. An ancillary analysis of the CHIVA phase II GINECO trial. Gynecol Oncol. 2025 Jan;192:145-154. doi: 10.1016/j.ygyno.2024.12.004. Epub 2024 Dec 12.

    PubMed 39671779

  • Yaniz-Galende E, Zeng Q, Bejar-Grau JF, Klein C, Blanc-Durand F, Le Formal A, Pujade-Lauraine E, Chardin L, Edmond E, Marty V, Ray-Coquard I, Joly F, Ferron G, Pautier P, Berton-Rigaud D, Lortholary A, Dohollou N, Desauw C, Fabbro M, Malaurie E, Bonichon-Lamaichhane N, Bello Roufai D, Gantzer J, Rouleau E, Genestie C, Leary A. Spatial Profiling of Ovarian Carcinoma and Tumor Microenvironment Evolution under Neoadjuvant Chemotherapy. Clin Cancer Res. 2024 Jul 1;30(13):2790-2800. doi: 10.1158/1078-0432.CCR-23-3836.

    PubMed 38669064

  • Gaitskell K, Rogozinska E, Platt S, Chen Y, Abd El Aziz M, Tattersall A, Morrison J. Angiogenesis inhibitors for the treatment of epithelial ovarian cancer. Cochrane Database Syst Rev. 2023 Apr 18;4(4):CD007930. doi: 10.1002/14651858.CD007930.pub3.

    PubMed 37185961

  • Ferron G, De Rauglaudre G, Becourt S, Delanoy N, Joly F, Lortholary A, You B, Bouchaert P, Malaurie E, Gouy S, Kaminsky MC, Meunier J, Alexandre J, Berton D, Dohollou N, Dubot C, Floquet A, Favier L, Venat-Bouvet L, Fabbro M, Louvet C, Lotz JP, Abadie-Lacourtoisie S, Desauw C, Del Piano F, Leheurteur M, Bonichon-Lamichhane N, Rastkhah M, Follana P, Gantzer J, Ray-Coquard I, Pujade-Lauraine E. Neoadjuvant chemotherapy with or without nintedanib for advanced epithelial ovarian cancer: Lessons from the GINECO double-blind randomized phase II CHIVA trial. Gynecol Oncol. 2023 Mar;170:186-194. doi: 10.1016/j.ygyno.2023.01.008. Epub 2023 Jan 25.

    PubMed 36706645

  • Aide N, Fauchille P, Coquan E, Ferron G, Combe P, Meunier J, Alexandre J, Berton D, Leary A, De Rauglaudre G, Bonichon N, Pujade Lauraine E, Joly F. Predicting tumor response and outcome of second-look surgery with 18F-FDG PET/CT: insights from the GINECO CHIVA phase II trial of neoadjuvant chemotherapy plus nintedanib in stage IIIc-IV FIGO ovarian cancer. Eur J Nucl Med Mol Imaging. 2021 Jun;48(6):1998-2008. doi: 10.1007/s00259-020-05092-3. Epub 2020 Nov 21.

    PubMed 33221969

  • Robelin P, Tod M, Colomban O, Lachuer J, Ray-Coquard I, Rauglaudre G, Joly F, Chevalier-Place A, Combe P, Lortholary A, Hamizi S, Raban N, Ferron G, Meunier J, Berton-Rigaud D, Alexandre J, Kaminsky MC, Dubot C, Leary A, Malaurie E, You B. Comparative analysis of predictive values of the kinetics of 11 circulating miRNAs and of CA125 in ovarian cancer during first line treatment (a GINECO study). Gynecol Oncol. 2020 Oct;159(1):256-263. doi: 10.1016/j.ygyno.2020.07.021. Epub 2020 Jul 22.

    PubMed 32712155

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing vargatef in people with Ovarian Cancer, run by ARCAGY/ GINECO GROUP at 36 sites in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 42 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 36 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Median Progression-free Survival (PFS) in each study arm (time frame: average of 18 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01583322, which also lists 7 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Sep 2023.

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