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

NCT01583322 | Completed Phase 2 DMC

• 1 other identifier: GINECO-OV119
• Study Type: interventional
• Target: 188
• Locations: 1 country
• Sites: 36

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).

Conditions

Ovarian Cancer

Keywords

ovarian cancer; debulking surgery; interval debulking; vargatef; nintedanib; maintenance; first line; paclitaxel; carboplatin

Outcome Measures

Primary Outcomes (1)

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

  average of 18 months

Secondary Outcomes (1)

• Response rate

  2 months after beginning of treatment

Study Arms (2)

vargatef/Nintedanib

EXPERIMENTAL

Drug: vargatef

placebo

PLACEBO COMPARATOR

Drug: placebo

Interventions

vargatef DRUG

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.

vargatef/Nintedanib

placebo DRUG

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.

placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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,

You may not qualify if:

• 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,

Sponsors & Collaborators

• ARCAGY/ GINECO GROUP: lead

Study Sites (36)

Centre Paul Papin

Angers, France

Location

Institut Ste Catherine

Avignon, France

Location

Clinique Tivoli

Bordeaux, France

Location

Institut Bergonié

Bordeaux, France

Location

Polyclinique Bordeaux Nord

Bordeaux, France

Location

Centre François Baclesse

Caen, France

Location

Centre Jean Perrin

Clermont-Ferrand, France

Location

Centre Hospitalier Alpes Leman

Contamine-sur-Arve, France

Location

Centre Hospitalier Intercommunal de Créteil

Créteil, France

Location

Centre Hospitalier de Dax

Dax, France

Location

Centre Georges François Leclerc

Dijon, France

Location

Centre Hospitalier Régional Universitaire de Lille - Hôpital Huriez

Lille, France

Location

Centre Oscar Lambret

Lille, France

Location

Centre Hospitalier Universitaire Dupuytren

Limoges, France

Location

Centre Léon bérard

Lyon, France

Location

ICM Val d'Aurelle

Montpellier, France

Location

Centre Catherine de Sienne

Nantes, France

Location

Hôpital Privé du Confluent S.A.S.

Nantes, France

Location

Centre Antoine Lacassagne

Nice, France

Location

Centre Hospitalier Régional

Orléans, France

Location

Hôpital Cochin

Paris, France

Location

Hôpital Européen Georges Pompidou

Paris, France

Location

Hôpital Tenon

Paris, France

Location

Institut Mutualiste Montsouris-Jourdan

Paris, France

Location

Centre Hospitalier Lyon-sud

Pierre-Bénite, France

Location

Milétrie - Centre Hospitalier Universitaire de Poitiers

Poitiers, France

Location

Institut Jean Godinot

Reims, France

Location

Centre Henri Becquerel

Rouen, France

Location

Clinique Armoricaine de Radiologie

Saint-Brieuc, France

Location

Hôpital René Huguenin

Saint-Cloud, France

Location

ICO René Gauducheau

Saint-Herblain, France

Location

Hôpital Civil

Strasbourg, France

Location

Hôpitaux Du Leman

Thonon-les-Bains, France

Location

Centre Claudius Régaud

Toulouse, France

Location

Institut de Cancérologie de Lorraine

Vandœuvre-lès-Nancy, France

Location

Gustave Roussy

Villejuif, France

Location

Related Publications (7)

• 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.

  PMID: 41284952 DERIVED

• 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.

  PMID: 39671779 DERIVED

• 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.

  PMID: 38669064 DERIVED

• 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.

  PMID: 37185961 DERIVED

• 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.

  PMID: 36706645 DERIVED

• 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.

  PMID: 33221969 DERIVED

• 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.

  PMID: 32712155 DERIVED

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

nintedanib

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Study Officials

• Gwénaël Ferron, MD

  Institut Claudius Régaud

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 19, 2012
• First Posted: April 24, 2012
• Study Start: June 1, 2012
• Primary Completion: May 1, 2015
• Study Completion: March 1, 2016
• Last Updated: September 6, 2023

Record last verified: 2023-09

Locations

FR (36)