A Study to Evaluate Lucitanib in Combination With Nivolumab in Patients With a Solid Tumor

Advanced Solid Tumor Clinical Trial

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

Clinical Trial Details — Status: Suspended

Administrative data

• NCT number: NCT04042116
• Other study ID #: CO-3810-101
• Secondary ID: ENGOT-GYN3/AGO/L
• Status: Suspended
• Phase: Phase 1/Phase 2
• Start date: July 29, 2019
• Est. completion date: January 2024

Study information

• Verified date: December 2022
• Source: Clovis Oncology, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

Recruitment information / eligibility

• Status: Suspended
• Enrollment: 227
• Est. completion date: January 2024
• Est. primary completion date: July 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Advanced Solid Tumor
• Gynecologic Cancer
• Neoplasms

Intervention

Drug:
• Lucitanib
Oral lucitanib will be administered once daily (QD) at the starting dose of 6 mg.
• Lucitanib
Oral lucitanib will be administered once daily (QD). The dose will be 6 mg.
• Lucitanib
Oral lucitanib will be administered once daily (QD) at the starting dose of 6 mg. Subjects will be allowed to intrapatient dose escalate in increments of 2 mg up to a total dose of 10 mg QD lucitanib if they meet the study specific clinical criteria.
• Nivolumab
IV nivolumab 480 mg will be administered once every 4 weeks.

Locations

Country	Name	City	State
Austria	Medical University of Innsbruck	Innsbruck
Belgium	Saint Luc Univerisity Hospital	Brussels
Belgium	University Hospital Ghent	Ghent
Belgium	University Hospitals Leuven, Campus Gasthuisberg	Leuven
Germany	University Hospital Carl Gustav Carus	Dresden
Germany	Kliniken Essen-Mitte	Essen
Germany	University Hospital Mannhein	Mannheim
Italy	Polyclinic S. Orsola-Malpighi	Bologna
Italy	National Cancer Institute -IRCCS "Fondazione G. Pascale	Naples
Italy	Foundation IRCCS Hospital Agostino Gemelli	Rome
Spain	University Hospital Vall d'Hebron	Barcelona
Spain	University Hospital Reina Sofia	Cordoba	Andalusia
Spain	La Paz University Hospital	Madrid
Spain	Navarra University Clinic	Madrid
United States	Anschutz Cancer Pavilion	Aurora	Colorado
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Ohio State University Wexner Medical Center	Columbus	Ohio
United States	Duke University School of Medicine	Durham	North Carolina
United States	UCLA Jonsson Comprehensive Cancer Center	Los Angeles	California
United States	Tennessee Oncology	Nashville	Tennessee
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	NYU Langone Laura and Isaac Perlmutter Cancer Center	New York	New York
United States	Stephenson Cancer Center	Oklahoma City	Oklahoma
United States	Magee-Womens Hospital of UPMC	Pittsburgh	Pennsylvania
United States	UC San Diego Moores Cancer Center	San Diego	California
United States	Florida Cancer Specialists	Sarasota	Florida
United States	Swedish Cancer Institute	Seattle	Washington

Sponsors (3)

Lead Sponsor	Collaborator
Clovis Oncology, Inc.	Bristol-Myers Squibb, European Network of Gynaecological Oncological Trial Groups (ENGOT)

Countries where clinical trial is conducted

United States,  Austria,  Belgium,  Germany,  Italy,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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	Acute and long-term safety and tolerability of the combination (Phase 2)	Incidence of AEs, clinical lab abnormalities, and dose modifications.	From first dose of study drug until disease progression (up to approximately 2 years)
Secondary	Further evaluation of preliminary efficacy of combination (Phase 2)	Duration of response, progression-free survival, and disease control per RECIST v1.1, overall survival.	From first dose of study drug until at least 100 days after end of treatment (up to approximately 2 years)
Secondary	Lucitanib PK Profile at Steady State [Phase 1 dose escalation and Food Effect]	Area under the curve [AUCss]	From first dose of study drug to the end of Cycle 1 (each cycle is 28 days)
Secondary	Lucitanib PK Profile at Steady State [Phase 1 dose escalation and Food Effect]	Maximum plasma concentration [Cmax,ss]	From first dose of study drug to the end of Cycle 1 (each cycle is 28 days)
Secondary	Lucitanib PK Profile at Steady State [Phase 1 dose escalation and Food Effect]	Total clearance of drug after oral administration [CLss/F]	From first dose of study drug to the end of Cycle 1 (each cycle is 28 days)
Secondary	Lucitanib PK Profile at Steady State [Phase 1 dose escalation and Food Effect, Phase 2]	Minimum plasma concentration [Cmin,ss]	From Cycle 2 to Cycle 5 (each cycle is 28 days)
Secondary	Lucitanib PK Profile at single dose [Food Effect Cohort]	Area under the curve [AUC]	From first dose of study drug to Day -1
Secondary	Lucitanib PK Profile at single dose [Food Effect Cohort]	Maximum plasma concentration [Cmax]	From first dose of study drug to Day -1
Secondary	Lucitanib PK Profile at single dose [Food Effect Cohort]	Time to maximum plasma concentration [Tmax]	From first dose of study drug to Day -1
Secondary	The effect of food (fasted or fed) on the Lucitanib PK Profile [Food Effect Cohort]	Area under the curve [AUC]	From first dose of study drug to Day -1
Secondary	The effect of food (fasted or fed) on the Lucitanib PK Profile [Food Effect Cohort]	Maximum plasma concentration [Cmax]	From first dose of study drug to Day -1
Secondary	The effect of food (fasted or fed) on the Lucitanib PK Profile [Food Effect Cohort]	Time to maximum plasma concentration [Tmax]	From first dose of study drug to Day -1