Combination Chemotherapy With Nintedanib / Placebo in Endometrial Cancer

NCT02730416 | Completed Phase 2 DMC

• 1 other identifier: ENGOT-EN1/FANDANGO
• Study Type: interventional
• Target: 146
• Locations: 7 countries
• Sites: 37

Brief Summary

This study will evaluate the role of addition of an anti-angiogenic agent (Nintedanib/placebo) to conventional combination chemotherapy as concomitant and maintenance treatment in primary advanced or with first relapse of endometrial cancer.

Conditions

Endometrial Cancer

Outcome Measures

Primary Outcomes (1)

• PFS: Difference in months of Median Progression-Free Survival in experimental arm versus comparator arm

  Superiority of Nintedanib arm vs. placebo arm by median PFS increase of 4 months (from 10 months to 14 months) HR: 1.4; power80%; one-sided alpha: 15%. Inclusion period 18 months. Median PFS matures after 14 months of end inclusion

  36 months

Secondary Outcomes (11)

• PFS in the sub-populations as described under stratification factors

  32 months

• PFS after consecutive treatment (PFS2). To be measured (in months) and reported

  48 months

• Disease Specific Survival (DSS)

  48 months

• TSST (Time to Second Subsequent Therapy)

  48 months

• TFST (Time to First Subsequent Therapy)

  48 months

Study Arms (2)

A: Nintedanib

EXPERIMENTAL

Nintedanib 200mg twice daily days 2-21 every 21 days for 6 courses during simultaneous treatment with carboplatin-paclitaxel; afterwards in maintenance 200mg twice daily days 1-21 every 21 days. Treatment continues until progression or unacceptable toxicity.

Drug: Nintedanib or Placebo; Carboplatin, Paclitaxel

B: Placebo

PLACEBO COMPARATOR

Placebo twice daily days 2-21 every 21 days for 6 courses during simultaneous treatment with carboplatib-paclitaxel; afterwards in maintenance 200mg twice daily days 1-21 every 21 days. Treatment continues until progression or unacceptable toxicity.

Drug: Nintedanib or Placebo; Carboplatin, Paclitaxel

Interventions

Nintedanib or Placebo; Carboplatin, Paclitaxel DRUG

Arm A: Nintedanib: 200mg orally twice daily d 2-21 q 21 days x 6 courses; afterwards daily dosing, until PD Arm B: Placebo: orally twice daily d 2-21 q 21 days x 6 courses; afterwards daily dosing, until PD In both arms: 6 courses of standard carboplatin and paclitaxel: Carboplatin AUC 5 iv every 21 days; Paclitaxel 175mg/m2 iv every 21 days. Both drugs are continued for maximum six courses or until unacceptable toxicity

A: Nintedanib; B: Placebo

Eligibility Criteria

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

You may qualify if:

• Histological confirmed endometrial cancer. (FIGO 2009)
• Stage 3C 2
• Stage 4 A \& B
• Relapsed after adjuvant therapy for stage 1-3 disease
• Patients may have undergone primary surgery.
• Patients may have received adjuvant chemotherapy for stage 1 - 3.
• Patients may have received vaginal brachytherapy
• Patients may have received external beam radiotherapy. Patients who are to be enrolled for stage 3C2 diseases are allowed to receive external beam radiotherapy prior to trial entry.
• Patients may have received hormonal treatment
• Patients must have measurable disease or non-measurable disease on CT scan according to RECIST 1.1 outside irradiated field. For stage 3C2 disease patients without measureable or non-measureable disease are accepted.
• Patients must give informed consent
• ECOG performance status of 0 -1
• Patients must have an adequate organ function
• Life expectancy of at least 12 weeks
• Patients must be fit to receive combination chemotherapy

You may not qualify if:

• Sarcomas, small cell carcinoma with neuroendocrine differentiation or non-epithelial cancers.
• Concurrent cancer therapy
• Previous Chemotherapy for stage 4 disease or for relapsed disease.
• Previous treatment with anti-angiogenic/anti VEGF therapy including nintedanib.
• Concurrent treatment with an investigational agent or participation in another clinical trial.
• Treatment within 28 days prior to randomisation with any investigational drug, radiotherapy, immunotherapy, chemotherapy, hormonal therapy or biological therapy. Palliative radiotherapy may be permitted for symptomatic control of pain from bone metastases in extremities, provided that the radiotherapy does not involve target lesions, and the reason for the radiotherapy does not reflect progressive disease.
• Major injuries or surgery within the past 21 days prior to start of study treatment with incomplete wound healing and/or planned surgery during the on-treatment study period.
• Relapse within six months after adjuvant chemotherapy (treatment-free interval \< 182 days).
• Previous malignant disease, except patients with other malignant disease, for which the patient has been disease-free for at least three years. Concurrent other malignant disease except for curatively treated carcinoma in situ of the cervix or basal cell carcinoma of the skin.
• Active infection or other serious underlying medical condition, which might prevent the patient from receiving treatment or to be followed.
• Evidence of significant medical illness, abnormal laboratory finding or psychiatric illness/social situation that would, in the Investigator's judgement, make the patient inappropriate for this study.
• Known contraindications to VEGF directed therapy Target Disease Exceptions
• Known uncontrolled hypersensitivity to the investigational drugs.
• History of major thromboembolic event defined as:
• Uncontrolled pulmonary embolism (PE)

Sponsors & Collaborators

• Nordic Society of Gynaecological Oncology - Clinical Trials Unit: lead
• North Eastern German Society of Gynaecological Oncology: collaborator
• Belgian Gynaecological Oncology Group: collaborator
• ARCAGY/ GINECO GROUP: collaborator

Study Sites (37)

Onze Lieve Vrouwziekenhuis

Aalst, 9300, Belgium

Location

Cliniques universitaires Saint-Luc

Brussels, 1200, Belgium

Location

Antwerp University Hospital

Edegem, 2650, Belgium

Location

Ghent University Hospital

Ghent, 9000, Belgium

Location

University Hospitals Leuven

Leuven, 3000, Belgium

Location

Odense Universitetshospital

Odense, Fyn, 5000, Denmark

Location

Aalborg Universitetshospital

Aalborg, Jylland, 9000, Denmark

Location

Vejle Sygehus

Vejle, Jylland, 7100, Denmark

Location

Rigshospitalet

Copenhagen, Region Sjælland, 2100, Denmark

Location

Kuopio University Hospital

Kuopio, 70029, Finland

Location

Tampere University Hospital

Tampere, 33520, Finland

Location

Institute Bergonié

Bordeaux, 33076, France

Location

Centre François Baclesse

Caen, 14076, France

Location

Centre Oscar Lambret

Lille, 59020, France

Location

Léon Bérard Center

Lyon, 69008, France

Location

Institut Paoli Calmettes

Marseille, 13009, France

Location

ICM (Cancer Institute of Montpellier)

Montpellier, France

Location

Centre Antoine Lacassagne

Nice, 06189, France

Location

Hospital Group Diaconesses Croix Saint-Simon

Paris, 75012, France

Location

Private Hospital Of Côtes D'armor

Plérin, 22 190, France

Location

Institut de Cancérologie de l'Ouest

Saint-Herblain, 44800, France

Location

Charité Campus Virchow Clinic

Berlin, 13353, Germany

Location

Klinik Chemnitz gGmbH

Chemnitz, 09116, Germany

Location

University Hospital Carl Gustav Carus Dresden

Dresden, 01307, Germany

Location

Universitätsklinikum Essen

Essen, 45122, Germany

Location

Kliniken Essen Mitte

Essen, 45135, Germany

Location

Center of Gynecology and Obstetrics

Frankfurt, 60596, Germany

Location

Universitätsklinikum Hamburg-Eppendorf

Hamburg, 20246, Germany

Location

St. Vincentius-Kliniken gAG Frauenklinik mit Hebammenlehranstalt

Karlsruhe, 76137, Germany

Location

Universitätsfrauenklinik Mainz

Mainz, 55131, Germany

Location

Universitätsfrauenklinik am Klinikum Südstadt Rostock

Rostock, 18059, Germany

Location

Universitätsfrauenklinik Ulm

Ulm, 89075, Germany

Location

Oslo University Hospital

Oslo, 0450, Norway

Location

Linköping University Hospital

Linköping, 58185, Sweden

Location

Skåne University Hospital

Lund, 221 85, Sweden

Location

Karolinska University Hospital

Stockholm, 171 76, Sweden

Location

Uppsala University Hospital

Uppsala, 751 85, Sweden

Location

MeSH Terms

Conditions

Endometrial Neoplasms

Interventions

nintedanib; Carboplatin; Paclitaxel

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Study Officials

• Mansoor R Mirza, MD

  NSGO

  STUDY CHAIR

Study Design

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

Study Record Dates

• First Submitted: January 14, 2016
• First Posted: April 6, 2016
• Study Start: December 12, 2016
• Primary Completion: October 20, 2021
• Study Completion: November 25, 2021
• Last Updated: July 29, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: From January 2024.

Locations

FR (10); DE (11); NO (1); FI (2); SE (4); DK (4); BE (5)