A Study to Evaluate Lucitanib in Combination With Nivolumab in Patients With a Solid Tumor
- Conditions
- Advanced Solid TumorGynecologic Cancer
- Interventions
- Registration Number
- NCT04042116
- Lead Sponsor
- Clovis Oncology, Inc.
- 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)
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- SUSPENDED
- Sex
- All
- Target Recruitment
- 227
- ≥ 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
- 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)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Phase 1b: Dose Escalation Lucitanib - Up to 50 patients with advanced solid tumor Phase 1b: Dose Escalation Nivolumab - Up to 50 patients with advanced solid tumor Phase 1b: Food Effect Cohort Nivolumab - Approximately 16 evaluable patients with an advanced, metastatic solid tumor will be enrolled Phase 2: Expansion Cohort - Endometrial Cancer Lucitanib * 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 Phase 2: Expansion Cohort - Ovarian Cancer Lucitanib * 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 Phase 2: Expansion Cohort - Endometrial Cancer Nivolumab * 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 Phase 2: Expansion Cohort - Ovarian Cancer Nivolumab * 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 Phase 2: Expansion Cohort - Clear Cell Cancer Nivolumab * Recurrent, metastatic clear cell carcinoma of ovarian, fallopian tube, primary peritoneal or endometrial origin * At least 1 prior platinum- and taxane-based chemotherapy regimen Phase 2: Expansion Cohort - Cervical Cancer Nivolumab * 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 Phase 1b: Food Effect Cohort Lucitanib - Approximately 16 evaluable patients with an advanced, metastatic solid tumor will be enrolled Phase 2: Expansion Cohort - Clear Cell Cancer Lucitanib * Recurrent, metastatic clear cell carcinoma of ovarian, fallopian tube, primary peritoneal or endometrial origin * At least 1 prior platinum- and taxane-based chemotherapy regimen Phase 2: Expansion Cohort - Cervical Cancer Lucitanib * 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
- Primary Outcome Measures
Name Time Method Best Overall Response Rate (Phase 2) From first dose of study drug until disease progression (up to approximately 2 years) 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.
Determine the recommended Phase 2 dose of the combination of lucitanib and nivolumab (Phase 1b) First dose of study drug through at least 100 days after end of treatment (up to approximately 2 years) Incidence of adverse events and clinical lab abnormalities defined as dose-limiting toxicities and maximum tolerated dose.
- Secondary Outcome Measures
Name Time Method Lucitanib PK Profile at Steady State [Phase 1 dose escalation and Food Effect, Phase 2] From Cycle 2 to Cycle 5 (each cycle is 28 days) Minimum plasma concentration \[Cmin,ss\]
The effect of food (fasted or fed) on the Lucitanib PK Profile [Food Effect Cohort] From first dose of study drug to Day -1 Time to maximum plasma concentration \[Tmax\]
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) Duration of response, progression-free survival, and disease control per RECIST v1.1, overall survival.
Lucitanib PK Profile at single dose [Food Effect Cohort] From first dose of study drug to Day -1 Time to maximum plasma concentration \[Tmax\]
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) Incidence of AEs, clinical lab abnormalities, and dose modifications.
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) Total clearance of drug after oral administration \[CLss/F\]
Trial Locations
- Locations (27)
Magee-Womens Hospital of UPMC
🇺🇸Pittsburgh, Pennsylvania, United States
Swedish Cancer Institute
🇺🇸Seattle, Washington, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
University Hospital Carl Gustav Carus
🇩🇪Dresden, Germany
National Cancer Institute -IRCCS "Fondazione G. Pascale
🇮🇹Naples, Italy
Foundation IRCCS Hospital Agostino Gemelli
🇮🇹Rome, Italy
Saint Luc Univerisity Hospital
🇧🇪Brussels, Belgium
Anschutz Cancer Pavilion
🇺🇸Aurora, Colorado, United States
Duke University School of Medicine
🇺🇸Durham, North Carolina, United States
Tennessee Oncology
🇺🇸Nashville, Tennessee, United States
Stephenson Cancer Center
🇺🇸Oklahoma City, Oklahoma, United States
University Hospital Reina Sofia
🇪🇸Cordoba, Andalusia, Spain
La Paz University Hospital
🇪🇸Madrid, Spain
UCLA Jonsson Comprehensive Cancer Center
🇺🇸Los Angeles, California, United States
UC San Diego Moores Cancer Center
🇺🇸San Diego, California, United States
Florida Cancer Specialists
🇺🇸Sarasota, Florida, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Navarra University Clinic
🇪🇸Madrid, Spain
Kliniken Essen-Mitte
🇩🇪Essen, Germany
University Hospital Mannhein
🇩🇪Mannheim, Germany
University Hospital Vall d'Hebron
🇪🇸Barcelona, Spain
University Hospitals Leuven, Campus Gasthuisberg
🇧🇪Leuven, Belgium
NYU Langone Laura and Isaac Perlmutter Cancer Center
🇺🇸New York, New York, United States
Ohio State University Wexner Medical Center
🇺🇸Columbus, Ohio, United States
Medical University of Innsbruck
🇦🇹Innsbruck, Austria
University Hospital Ghent
🇧🇪Ghent, Belgium
Polyclinic S. Orsola-Malpighi
🇮🇹Bologna, Italy