NCT02009579

Brief Summary

Indication: Treatment of subjects with advanced (FIGO stage IVB) or recurrent cervical cancer, prior radiochemotherapy or neo-adjuvant chemotherapy is allowed. Study design: This is a phase II randomized, double blind and placebo controlled trial evaluating the efficacy of Nintedanib/placebo in combination with the standard carboplatin and paclitaxel followed by Nintedanib/placebo maintenance in the treatment of patients with advanced or recurrent cervical cancer. A total of 120 patients will be randomized between the experimental and control arm in a 1:1 ratio. Randomization will be stratified for 1previous chemotherapy for metastatic disease (yes/no) and 2disease status (Stage IVB primary versus recurrent disease). Experimental arm: Subjects will receive 6 cycles of 3-weekly carboplatin (AUC 5) + paclitaxel (175 mg/m2) and Nintedanib 200 mg BID followed by Nintedanib maintenance until progression or for a total maximum duration of 120 weeks. Control arm: Subjects will receive 6 cycles of 3-weekly carboplatin (AUC 5) + paclitaxel (175 mg/m2) and placebo 200 mg BID followed by placebo maintenance until progression or for a total maximum duration of 120 weeks. Subjects without evidence of disease progression after completion or discontinuation of the study treatment will be followed until radiographic disease progression, withdrawal of consent or death.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
120

participants targeted

Target at P50-P75 for phase_2

Timeline
Completed

Started Mar 2014

Longer than P75 for phase_2

Geographic Reach
4 countries

32 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

October 24, 2013

Completed
2 months until next milestone

First Posted

Study publicly available on registry

December 12, 2013

Completed
3 months until next milestone

Study Start

First participant enrolled

March 1, 2014

Completed
6.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2021

Completed
2.7 years until next milestone

Study Completion

Last participant's last visit for all outcomes

October 1, 2023

Completed
Last Updated

August 7, 2024

Status Verified

August 1, 2024

Enrollment Period

6.8 years

First QC Date

October 24, 2013

Last Update Submit

August 6, 2024

Conditions

Uterine Cervical Neoplasms

Keywords

Uterine Cervical CancerPaclitaxelCarboplatinNintedanib

Outcome Measures

Primary Outcomes (1)

  • Progression free survival

    Primary objective: The purpose of this trial is to determine if chemotherapy (carboplatin/paclitaxel) plus Nintedanib (BIBF 1120) can improve progression free survival compared to chemotherapy (carboplatin/paclitaxel) plus placebo in patients with advanced or recurrent cervical cancer.

    1.5 years after LPI

Secondary Outcomes (4)

  • Safety and toxicity

    5 years after LPI

  • Overall survival

    5 years after LPI

  • Patient health status

    5 years after LPI

  • Overall survival

    5 years after LPI

Study Arms (2)

Experimental arm

ACTIVE COMPARATOR

Nintedanib/vargatef

Drug: Nintedanib

Comparator arm

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

NintedanibDRUG

Subjects will receive 6 cycles of 3-weekly carboplatin (AUC 5) + paclitaxel (175 mg/m2) and Nintedanib 200 mg BID followed by Nintedanib maintenance until progression or for a total maximum duration of 120 weeks.

Also known as: Vargatef
Experimental arm
PlaceboDRUG

Subjects will receive 6 cycles of 3-weekly carboplatin (AUC 5) + paclitaxel (175 mg/m2) and placebo 200 mg BID followed by placebo maintenance until progression or for a total maximum duration of 120 weeks.

Comparator arm

Eligibility Criteria

Age18 Years+
Sexfemale
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Female subjects more than 18 years of age
  • Histologically or cytologically confirmed advanced (\[FIGO\] stage IVB), or recurrent/persistent squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix will be eligible.
  • Prior treatment with angiogenesis inhibitors is allowed
  • Up to one prior line of chemotherapy for metastatic cervical cancer is allowed.
  • Treatment of primary disease with concomitant cisplatinum chemotherapy during radiotherapy is allowed and does not count as a line of chemotherapy for metastatic disease.
  • Treatment of primary disease with neoadjuvant chemotherapy before radical local surgery is allowed and does not count as a line of chemotherapy for metastatic disease.
  • Treatment of primary disease with neoadjuvant chemotherapy before radical local surgery followed by adjuvant radiochemotherapy is allowed and does not count as a line of chemotherapy for metastatic disease.
  • Treatment of primary disease with neoadjuvant chemotherapy before radical local surgery followed by adjuvant radiotherapy is allowed and does not count as a line of chemotherapy for metastatic disease.
  • Life expectancy at least 3 months.
  • ECOG Performance status score of 0 or 1
  • At least one measurable lesion according to RECIST 1.1 criteria
  • Signed and dated written informed consent prior to admission to the study in accordance with ICH-GCP guidelines and to the local legislation

You may not qualify if:

  • Known hypersensitivity to the trial drugs or to their excipients (including peanut or soya).
  • Brain or leptomeningeal metastases.
  • Centrally located tumors with radiographic evidence (CT or MRI) of local invasion of major blood vessels.
  • Tumor infiltrating the mucosa of the bowel or bladder, or known fistulas between the tumor and the gastrointestinal or urinary tract.
  • Radiographic evidence of cavitary or necrotic tumours
  • Treatment with other investigational drugs or treatment in another clinical trial within the past 4 weeks before start of therapy or concomitantly with the trial.
  • Therapeutic anticoagulation with drugs requiring INR monitoring (except low-dose heparin and/or heparin flush as needed for maintenance of an in-dwelling intravenous devise) or anti-platelet therapy (except for low-dose therapy with acetylsalicylic acid \<325 mg per day).
  • Major injuries within the past 4 weeks prior to start of study treatment with incomplete wound healing and/or planned surgery during the on-treatment study period.
  • History of clinically significant haemorrhagic or thromboembolic event in the past 6 months.
  • Known inherited predisposition to bleeding or thrombosis.
  • Significant cardiovascular diseases ( i.e. uncontrolled hypertension, unstable angina within the past 6 months, history of infarction within the past 12 months prior to start of study treatment, congestive heart failure \> NYHA II, serious cardiac arrhythmia, pericardial effusion).
  • History of a cerebral vascular accident, transient ischemic attack or subarachnoid haemorrhage within the past 6 months.
  • Abnormal renal, liver or bone marrow function defined as:
  • Proteinuria CTCAE grade 2 or greater
  • Creatinin \> 2 ULN or GFR \< 30 ml/min
  • +12 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (32)

CHU Saint-Pierre

Brussels, Belgium

Location

Institut Jules Bordet

Brussels, Belgium

Location

Grand Hopital de Charleroi

Charleroi, Belgium

Location

UZ Antwerpen

Edegem, Belgium

Location

AZ Groeninge

Kortrijk, Belgium

Location

UZ Leuven

Leuven, 3000, Belgium

Location

CHU de Liège

Liège, 4000, Belgium

Location

CHR Citadelle

Liège, Belgium

Location

Clinique et maternite St. Elisabeth

Namur, Belgium

Location

Cliniques Universitaires mont godinne

Yvoir, Belgium

Location

Charité Med Uni Berlin

Berlin, Germany

Location

Universitätsklinikum Carl Gustav Carus Dresden

Dresden, Germany

Location

Kliniken Essen Mitte

Essen, Germany

Location

Georg-August University Göttingen

Göttingen, Germany

Location

Medical University Greifswald

Greifswald, Germany

Location

University Tübingen

Tübingen, Germany

Location

Centro Riferimento Oncologico

Aviano, Italy

Location

Spedali Civili

Brescia, Italy

Location

Azienda Ospedaliera Cannizzaro

Catania, Italy

Location

National Cancer Institute

Milan, Italy

Location

Istituto Nazionale Tumori-Pascale Naples

Naples, Italy

Location

Padova Istituti Oncologico Veneto

Padua, Italy

Location

University Pisa

Pisa, Italy

Location

AUSL Reggio Emilia

Reggio Emilia, Italy

Location

Poloclinico A Gemelli

Rome, Italy

Location

Mauriziano -Torino

Torino, Italy

Location

S. Anna Torino

Torino, Italy

Location

Hospital Provincial Reina Sofia

Córdoba, 14004, Spain

Location

H. Ramón y Cajal

Madrid, 28034, Spain

Location

Hospital Clinico San Carlos

Madrid, 28040, Spain

Location

Hospital Universitario Morales Meseguer

Murcia, 30008, Spain

Location

Hospital Son Llatzer

Palma Mallorca, 07198, Spain

Location

Related Links

MeSH Terms

Conditions

Uterine Cervical Neoplasms

Interventions

nintedanib

Condition Hierarchy (Ancestors)

Uterine NeoplasmsGenital Neoplasms, FemaleUrogenital NeoplasmsNeoplasms by SiteNeoplasmsUterine Cervical DiseasesUterine DiseasesGenital Diseases, FemaleFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesGenital Diseases

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

October 24, 2013

First Posted

December 12, 2013

Study Start

March 1, 2014

Primary Completion

January 1, 2021

Study Completion

October 1, 2023

Last Updated

August 7, 2024

Record last verified: 2024-08

Locations

IT(11)DE(6)BE(10)ES(5)