NCT04042116

Brief Summary

This is an open-label, Phase 1b/2 study to determine the recommended dose of lucitanib in combination with nivolumab in patients with an advanced solid tumor (Phase 1b); followed by evaluation of the safety and efficacy of lucitanib and nivolumab in patients with an advanced gynecological solid tumor (Phase 2) and evaluate the effects of dosing under fasting or fed state (Food Effect)

Trial Health

40
At Risk

Trial Health Score

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

Trial has exceeded expected completion date
Trial recruitment is currently suspended
Enrollment
227

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started Jul 2019

Longer than P75 for phase_1

Geographic Reach
6 countries

27 active sites

Status
suspended

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

July 19, 2019

Completed
10 days until next milestone

Study Start

First participant enrolled

July 29, 2019

Completed
3 days until next milestone

First Posted

Study publicly available on registry

August 1, 2019

Completed
3.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2023

Completed
6 months until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2024

Completed
Last Updated

December 20, 2022

Status Verified

December 1, 2022

Enrollment Period

3.9 years

First QC Date

July 19, 2019

Last Update Submit

December 16, 2022

Conditions

Keywords

lucitanibnivolumabantineoplastic agents immunologicalantineoplastic agentstyrosine kinase inhibitorsgynecologic neoplasmscheckpoint inhibitorovarian cancerfallopian tube cancerprimary peritoneal cancerendometrial cancerclear cell cancercervical cancerPD-1 inhibitorImmuno-oncology

Outcome Measures

Primary Outcomes (2)

  • Determine the recommended Phase 2 dose of the combination of lucitanib and nivolumab (Phase 1b)

    Incidence of adverse events and clinical lab abnormalities defined as dose-limiting toxicities and maximum tolerated dose.

    First dose of study drug through at least 100 days after end of treatment (up to approximately 2 years)

  • Best Overall Response Rate (Phase 2)

    Confirmed best overall response (PR or CR) based on investigator assessment of objective response according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

    From first dose of study drug until disease progression (up to approximately 2 years)

Secondary Outcomes (12)

  • Acute and long-term safety and tolerability of the combination (Phase 2)

    From first dose of study drug until disease progression (up to approximately 2 years)

  • Further evaluation of preliminary efficacy of combination (Phase 2)

    From first dose of study drug until at least 100 days after end of treatment (up to approximately 2 years)

  • Lucitanib PK Profile at Steady State [Phase 1 dose escalation and Food Effect]

    From first dose of study drug to the end of Cycle 1 (each cycle is 28 days)

  • Lucitanib PK Profile at Steady State [Phase 1 dose escalation and Food Effect]

    From first dose of study drug to the end of Cycle 1 (each cycle is 28 days)

  • Lucitanib PK Profile at Steady State [Phase 1 dose escalation and Food Effect]

    From first dose of study drug to the end of Cycle 1 (each cycle is 28 days)

  • +7 more secondary outcomes

Study Arms (6)

Phase 1b: Dose Escalation

EXPERIMENTAL

\- Up to 50 patients with advanced solid tumor

Drug: LucitanibDrug: Nivolumab

Phase 1b: Food Effect Cohort

EXPERIMENTAL

\- Approximately 16 evaluable patients with an advanced, metastatic solid tumor will be enrolled

Drug: LucitanibDrug: Nivolumab

Phase 2: Expansion Cohort - Endometrial Cancer

EXPERIMENTAL

* Recurrent endometrial carcinoma at least 1 prior platinum-based chemotherapy regimen * Up to 10 patients who have progressed on treatment with 1 prior PD-(L)1 inhibitor administered as monotherapy will be allowed to enroll

Drug: LucitanibDrug: Nivolumab

Phase 2: Expansion Cohort - Ovarian Cancer

EXPERIMENTAL

* Recurrent high grade epithelial ovarian, fallopian tube, or primary peritoneal cancer, of any histology excluding clear cell carcinoma * At least 2 prior chemotherapy regimens which at least 1 must have been platinum-doublet chemotherapy * Up to 10 subjects with recurrent ovarian, fallopian tube, or primary peritoneal cancer, of any histology excluding clear cell carcinoma who have progressed within 6 months after completing first-line platinum-based chemotherapy will be allowed to enroll

Drug: LucitanibDrug: Nivolumab

Phase 2: Expansion Cohort - Clear Cell Cancer

EXPERIMENTAL

* Recurrent, metastatic clear cell carcinoma of ovarian, fallopian tube, primary peritoneal or endometrial origin * At least 1 prior platinum- and taxane-based chemotherapy regimen

Drug: LucitanibDrug: Nivolumab

Phase 2: Expansion Cohort - Cervical Cancer

EXPERIMENTAL

* Persistent or recurrent cervix cancer of squamous carcinoma, adenocarcinoma, or adenosquamous carcinoma histology * At least 1 prior regimen of platinum-based chemotherapy, with or without bevacizumab, for metastatic disease

Drug: LucitanibDrug: Nivolumab

Interventions

Oral lucitanib will be administered once daily (QD) at the starting dose of 6 mg.

Also known as: CO-3810
Phase 1b: Dose Escalation

IV nivolumab 480 mg will be administered once every 4 weeks.

Also known as: Opdivo, BMS-936558
Phase 1b: Dose EscalationPhase 1b: Food Effect CohortPhase 2: Expansion Cohort - Cervical CancerPhase 2: Expansion Cohort - Clear Cell CancerPhase 2: Expansion Cohort - Endometrial CancerPhase 2: Expansion Cohort - Ovarian Cancer

Eligibility Criteria

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

You may qualify if:

  • ≥ 18 years of age
  • Adequate organ function
  • Life expectancy ≥ 3 months
  • Women of childbearing potential must have a negative serum pregnancy test
  • Advanced/metastatic solid tumor (Phase 1b)
  • Availability of tumor tissue at screening
  • ECOG performance status of 0 to 1
  • Measurable disease (RECIST v1.1) (Phase 2)
  • Advanced, recurrent, or metastatic gynecological solid tumor (Phase 2)
  • Willing and able to fast, and to eat a high-fat breakfast (Food Effect)

You may not qualify if:

  • Prior treatment with lucitanib
  • Active second malignancy
  • Active central nervous system brain metastases
  • Pre-existing duodenal stent or any gastrointestinal disorder
  • Known history of HIV or AIDs; positive result of hepatitis B or C viruses
  • Evidence of interstitial lung disease, active pneumonitis, myocarditis, or history of myocarditis
  • Active, known or suspected autoimmune disease (eg, autoimmune hepatitis)
  • Condition requiring systemic treatment with corticosteroids or other immune suppressive medications
  • Unstable or uncontrolled hypertension (BP ≥ 140/90 mmHg)
  • Prior treatment with a VEGFR-tyrosine kinase inhibitor (Phase 2)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (27)

UCLA Jonsson Comprehensive Cancer Center

Los Angeles, California, 90095, United States

Location

UC San Diego Moores Cancer Center

San Diego, California, 92093, United States

Location

Anschutz Cancer Pavilion

Aurora, Colorado, 80045, United States

Location

Florida Cancer Specialists

Sarasota, Florida, 34232, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

NYU Langone Laura and Isaac Perlmutter Cancer Center

New York, New York, 10016, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Duke University School of Medicine

Durham, North Carolina, 27710, United States

Location

Ohio State University Wexner Medical Center

Columbus, Ohio, 43210, United States

Location

Stephenson Cancer Center

Oklahoma City, Oklahoma, 73104, United States

Location

Magee-Womens Hospital of UPMC

Pittsburgh, Pennsylvania, 15213, United States

Location

Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

Swedish Cancer Institute

Seattle, Washington, 98107, United States

Location

Medical University of Innsbruck

Innsbruck, 6020, Austria

Location

Saint Luc Univerisity Hospital

Brussels, 1200, Belgium

Location

University Hospital Ghent

Ghent, 9000, Belgium

Location

University Hospitals Leuven, Campus Gasthuisberg

Leuven, 3000, Belgium

Location

University Hospital Carl Gustav Carus

Dresden, 01307, Germany

Location

Kliniken Essen-Mitte

Essen, 45136, Germany

Location

University Hospital Mannhein

Mannheim, 68167, Germany

Location

Polyclinic S. Orsola-Malpighi

Bologna, 40138, Italy

Location

National Cancer Institute -IRCCS "Fondazione G. Pascale

Naples, 80131, Italy

Location

Foundation IRCCS Hospital Agostino Gemelli

Rome, 00168, Italy

Location

University Hospital Reina Sofia

Córdoba, Andalusia, 14004, Spain

Location

University Hospital Vall d'Hebron

Barcelona, 08035, Spain

Location

Navarra University Clinic

Madrid, 28027, Spain

Location

La Paz University Hospital

Madrid, 28046, Spain

Location

MeSH Terms

Conditions

Genital Neoplasms, FemaleOvarian NeoplasmsFallopian Tube NeoplasmsEndometrial NeoplasmsUterine Cervical Neoplasms

Interventions

E-3810Nivolumab

Condition Hierarchy (Ancestors)

Urogenital NeoplasmsNeoplasms by SiteNeoplasmsGenital Diseases, FemaleFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesGenital DiseasesEndocrine Gland NeoplasmsOvarian DiseasesAdnexal DiseasesEndocrine System DiseasesGonadal DisordersFallopian Tube DiseasesUterine NeoplasmsUterine DiseasesUterine Cervical Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulins

Study Officials

  • Erika Hamilton, MD

    Tennessee Oncology

    PRINCIPAL INVESTIGATOR
  • Nicole Concin, MD

    KEM Kliniken Essen Mitte Evang. Huyssens-Stiftung

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 19, 2019

First Posted

August 1, 2019

Study Start

July 29, 2019

Primary Completion

July 1, 2023

Study Completion

January 1, 2024

Last Updated

December 20, 2022

Record last verified: 2022-12

Data Sharing

IPD Sharing
Will share

De-identified datasets for study results will be made available to qualified researchers in compliance with applicable privacy laws and data protection regulations. Data will be provided by Clovis Oncology.

Shared Documents
STUDY PROTOCOL, SAP
Time Frame
Data will be made available to qualified researchers after the primary, secondary, and/or exploratory outcomes of the study are reported or published and for 1 year thereafter.
Access Criteria
Requests for de-identified datasets will be made available to qualified researchers following submission of a methodologically sound proposal to medinfo@clovisoncology.com.

Locations