Clinical trial NCT04042116: A Study to Evaluate Lucitanib in Combination With Nivolumab in Patients With a Solid Tumor
Official title: LIO-1: A Phase 1b/2, Open-Label Study to Evaluate the Safety and Efficacy of Lucitanib in Combination With Nivolumab in Patients With An Advanced, Metastatic Solid Tumor
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: PHASE1
PHASE2
Conditions: Advanced Solid Tumor
Gynecologic Cancer
Keywords: lucitanib
nivolumab
antineoplastic agents immunological
antineoplastic agents
tyrosine kinase inhibitors
gynecologic neoplasms
checkpoint inhibitor
ovarian cancer
fallopian tube cancer
primary peritoneal cancer
endometrial cancer
clear cell cancer
cervical cancer
PD-1 inhibitor
Immuno-oncology
Lead sponsor: Clovis Oncology, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Bristol-Myers Squibb
name: European Network of Gynaecological Oncological Trial Groups (ENGOT)
First posted: 2019-08-01
Enrollment: 227
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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)


Eligibility criteria: General Inclusion Criteria:

* ≥ 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)

General Exclusion Criteria:

* 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)

Primary outcomes:
measure: Determine the recommended Phase 2 dose of the combination of lucitanib and nivolumab (Phase 1b)
timeFrame: First dose of study drug through at least 100 days after end of treatment (up to approximately 2 years)
measure: Best Overall Response Rate (Phase 2)
timeFrame: From first dose of study drug until disease progression (up to approximately 2 years)
Secondary outcomes:
measure: Acute and long-term safety and tolerability of the combination (Phase 2)
timeFrame: From first dose of study drug until disease progression (up to approximately 2 years)
measure: Further evaluation of preliminary efficacy of combination (Phase 2)
timeFrame: From first dose of study drug until at least 100 days after end of treatment (up to approximately 2 years)
measure: Lucitanib PK Profile at Steady State [Phase 1 dose escalation and Food Effect]
timeFrame: From first dose of study drug to the end of Cycle 1 (each cycle is 28 days)
measure: Lucitanib PK Profile at Steady State [Phase 1 dose escalation and Food Effect]
timeFrame: From first dose of study drug to the end of Cycle 1 (each cycle is 28 days)
measure: Lucitanib PK Profile at Steady State [Phase 1 dose escalation and Food Effect]
timeFrame: From first dose of study drug to the end of Cycle 1 (each cycle is 28 days)
measure: Lucitanib PK Profile at Steady State [Phase 1 dose escalation and Food Effect, Phase 2]
timeFrame: From Cycle 2 to Cycle 5 (each cycle is 28 days)
measure: Lucitanib PK Profile at single dose [Food Effect Cohort]
timeFrame: From first dose of study drug to Day -1
measure: Lucitanib PK Profile at single dose [Food Effect Cohort]
timeFrame: From first dose of study drug to Day -1
measure: Lucitanib PK Profile at single dose [Food Effect Cohort]
timeFrame: From first dose of study drug to Day -1
measure: The effect of food (fasted or fed) on the Lucitanib PK Profile [Food Effect Cohort]
timeFrame: From first dose of study drug to Day -1
measure: The effect of food (fasted or fed) on the Lucitanib PK Profile [Food Effect Cohort]
timeFrame: From first dose of study drug to Day -1
measure: The effect of food (fasted or fed) on the Lucitanib PK Profile [Food Effect Cohort]
timeFrame: From first dose of study drug to Day -1
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA Jonsson Comprehensive Cancer Center
state: California
city: San Diego
country: United States
facility: UC San Diego Moores Cancer Center
state: California
city: Aurora
country: United States
facility: Anschutz Cancer Pavilion
state: Colorado
city: Sarasota
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: New York
country: United States
facility: NYU Langone Laura and Isaac Perlmutter Cancer Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Durham
country: United States
facility: Duke University School of Medicine
state: North Carolina
city: Columbus
country: United States
facility: Ohio State University Wexner Medical Center
state: Ohio
city: Oklahoma City
country: United States
facility: Stephenson Cancer Center
state: Oklahoma
city: Pittsburgh
country: United States
facility: Magee-Womens Hospital of UPMC
state: Pennsylvania
city: Nashville
country: United States
facility: Tennessee Oncology
state: Tennessee
city: Seattle
country: United States
facility: Swedish Cancer Institute
state: Washington
city: Innsbruck
country: Austria
facility: Medical University of Innsbruck
city: Brussels
country: Belgium
facility: Saint Luc Univerisity Hospital
city: Ghent
country: Belgium
facility: University Hospital Ghent
city: Leuven
country: Belgium
facility: University Hospitals Leuven, Campus Gasthuisberg
city: Dresden
country: Germany
facility: University Hospital Carl Gustav Carus
city: Essen
country: Germany
facility: Kliniken Essen-Mitte
city: Mannheim
country: Germany
facility: University Hospital Mannhein
city: Bologna
country: Italy
facility: Polyclinic S. Orsola-Malpighi
city: Naples
country: Italy
facility: National Cancer Institute -IRCCS "Fondazione G. Pascale
city: Rome
country: Italy
facility: Foundation IRCCS Hospital Agostino Gemelli
city: Cordoba
country: Spain
facility: University Hospital Reina Sofia
state: Andalusia
city: Barcelona
country: Spain
facility: University Hospital Vall d'Hebron
city: Madrid
country: Spain
facility: Navarra University Clinic
city: Madrid
country: Spain
facility: La Paz University Hospital
Study officials:
affiliation: Tennessee Oncology
name: Erika Hamilton, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: KEM Kliniken Essen Mitte Evang. Huyssens-Stiftung
name: Nicole Concin, MD
role: PRINCIPAL_INVESTIGATOR
References: