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A Study to Assess the Safety and Efficacy of the VEGFR-FGFR-PDGFR Inhibitor, Lucitanib, Given to Patients With Metastatic Breast Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02202746
Recruitment Status : Terminated (Sponsor decision to end monotherapy development of the compound in breast cancer.)
First Posted : July 29, 2014
Results First Posted : June 23, 2020
Last Update Posted : June 23, 2020
Sponsor:
Information provided by (Responsible Party):
Clovis Oncology, Inc.

Tracking Information
First Submitted Date  ICMJE July 25, 2014
First Posted Date  ICMJE July 29, 2014
Results First Submitted Date  ICMJE February 20, 2020
Results First Posted Date  ICMJE June 23, 2020
Last Update Posted Date June 23, 2020
Actual Study Start Date  ICMJE September 9, 2014
Actual Primary Completion Date January 17, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 20, 2020)
Progression Free Survival (PFS) According to RECIST Version 1.1 as Determined by the Investigator [ Time Frame: From Cycle 1 Day 1 until disease progression or end of treatment, whichever came first, assessed up to 29 months ]
The primary efficacy endpoint of PFS was calculated as 1+ the number of days from the date of first dose of study drug to disease progression or death due to any cause, whichever occurs first. Patients without a documented event of progression were censored on the date of their last adequate tumor assessment (i.e., radiologic assessment), or the date of randomization if no tumor assessments were performed. Progression events were determined by the investigator. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.
Original Primary Outcome Measures  ICMJE
 (submitted: July 25, 2014)
Progression-Free Survival (PFS) [ Time Frame: Screening, every 8 weeks; up to 2 years ]
Defined as 1+ the number of days from the date of randomization to disease progression or death due to any cause, whichever occurs first
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 20, 2020)
  • Objective Response Rate (ORR) by RECIST v1.1 [ Time Frame: From Cycle 1 Day 1 until disease progression or end of treatment, whichever came first, assessed up to 29 months ]
    ORR is the percentage of patients with a best response of CR or PR according to RECIST v1.1. The best response is recorded from the start of the treatment (Day 1) until disease progression or recurrence. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions, defined by and assessed as: Complete Response (CR), is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. Partial Response (PR), at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter.
  • Duration of Response (DR) by RECIST v1.1 [ Time Frame: From Cycle 1 Day 1 until disease progression or end of treatment, whichever came first, assessed up to 29 months ]
    DR for complete response (CR) and partial response (PR) was measured from the date that any of these best confirmed responses was first recorded until the first date that PD was objectively documented. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions, defined by and assessed as: Complete Response (CR), is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. Partial Response (PR), at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter.
  • Disease Control Rate (DCR) by RECIST v1.1 [ Time Frame: From Cycle 1 Day 1 until disease progression or end of treatment, whichever came first, assessed up to 29 months ]
    The DCR is defined as the percentage of patients with a best response rate of CR, PR, or SD for at least 12 weeks. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions, defined by and assessed as: Complete Response (CR), is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. Partial Response (PR), at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter. Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum longest diameter since the treatment started.
  • Comparative Pharmacokinetics (PK) of the Lucitanib Capsule Formulation vs. Tablet Formulation - Cmax [ Time Frame: Study Day -7 to Study Day 1, or approximately 8 days ]
    The comparative PK study was a within-patient comparison of tablet and capsule formulations of lucitanib administered orally. PK sampling was performed at specified time points on each of the following two days: • Day -7: patients received a single administration of 10 mg or 15 mg lucitanib tablet formulation • Day 1: patients received a single administration of 10 mg or 15 mg lucitanib in capsule formulation. Cmax = maximum concentration following administration of lucitanib.
  • Comparative Pharmacokinetics (PK) of the Lucitanib Capsule Formulation vs. Tablet Formulation - Tmax [ Time Frame: Study Day -7 to Study Day 1, or approximately 8 days ]
    The comparative PK study was a within-patient comparison of tablet and capsule formulations of lucitanib administered orally. PK sampling was performed at specified time points on each of the following two days: • Day -7: patients received a single administration of 10 mg or 15 mg lucitanib tablet formulation • Day 1: patients received a single administration of 10 mg or 15 mg lucitanib in capsule formulation. Tmax = time to maximum concentration following administration of lucitanib
  • Comparative Pharmacokinetics (PK) of the Lucitanib Capsule Formulation vs. Tablet Formulation - AUClast [ Time Frame: Study Day -7 to Study Day 1, or approximately 8 days ]
    The comparative PK study was a within-patient comparison of tablet and capsule formulations of lucitanib administered orally. PK sampling was performed at specified time points on each of the following two days: • Day -7: patients received a single administration of 10 mg or 15 mg lucitanib tablet formulation • Day 1: patients received a single administration of 10 mg or 15 mg lucitanib in capsule formulation. AUClast = area under the plasma concentration time curve from time 0 to the last quantifiable time point (24 hour)
  • Comparative Pharmacokinetics (PK) of the Lucitanib Capsule Formulation vs. Tablet Formulation - AUCinf [ Time Frame: Study Day -7 to Study Day 1, or approximately 8 days ]
    The comparative PK study was a within-patient comparison of tablet and capsule formulations of lucitanib administered orally. PK sampling was performed at specified time points on each of the following two days: • Day -7: patients received a single administration of 10 mg or 15 mg lucitanib tablet formulation • Day 1: patients received a single administration of 10 mg or 15 mg lucitanib in capsule formulation. AUCinf = area under the plasma concentration time curve from 0 to infinity
  • Relative Bioavailability Analysis for Tablet vs Capsule - Cmax, AUClast, AUCinf [ Time Frame: Study Day -7 to Study Day 1, or approximately 8 days ]
    Relative bioavailability of lucitanib was evaluated by comparison of (log-transformed) AUClast, Cmax and AUCinf of the tablet formulation to the capsule formulation using an analysis of variance (ANOVA) model with treatment as a fixed effect. The geometric means, ratio of the geometric means and 90% confidence intervals (CI) on the ratio of Tablet to Capsule (T:R) were presented for AUClast, Cmax and AUCinf. The CIs on the ratio of untransformed PK parameters were derived through reverse transformation of the 90% CI of the difference in the log scale to the 90% CI of the ratio in the original scale.
  • Overall Survival [ Time Frame: Cycle 1 Day 1 to date of death, assessed up to 29 months ]
    Overall survival (OS) is defined as the number of days from the date of first dose of study drug to the date of death (due to any cause). Patients without a known date of death will be censored on the date the patient was last known to be alive.
  • Change From Baseline in Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Total Score [ Time Frame: From Cycle 1 Day 1 until end of treatment, assessed up to 29 months ]
    FACT-B is used for assessment of health-related quality of life (QoL) in participants with breast cancer. It consists of 37 items, summarized to 5 subscales: physical (7 items), functional (7 items), social/family (7 items); all 3 ranged from 0 to 28, emotional (6 items) ranging from 0 to 24, and breast cancer subscale (10 items) ranging from 0 to 40; high subscale score represents a better QoL. All single-item measures range from 0='Not at all' to 4='Very much'. FACT-B Total Score is derived from adding the five subscale scores. Total possible score ranges from 0 to 148. High scale score represents a better QoL.
Original Secondary Outcome Measures  ICMJE
 (submitted: July 25, 2014)
  • Objective Response Rate (ORR) [ Time Frame: Screening, every 8 weeks; up to 2 years ]
    The best overall response recorded from the start of the treatment until disease progression or recurrence
  • Duration of Response (DR) [ Time Frame: Screening, every 8 weeks; up to 2 years ]
    DR for CR and PR will be measured from the date that any of these best responses is first recorded until the first date that PD is objectively documented
  • Disease Control Rate (DCR) [ Time Frame: Screening, every 8 weeks; up to 2 years ]
    The percentage of patients with a best response rate of CR, PR, or SD for at least 12 weeks
  • Overall Survival (OS) [ Time Frame: Continuously; up to 2 years ]
    Defined as 1+ the number of days from the date of randomization to death due to any cause
  • Safety Analyses [ Time Frame: Continuously; up to 2 years ]
    Incidence of adverse events (AEs), clinical laboratory abnormalities, and cardiac function, performed on all patients who have received at least one dose of lucitanib
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Assess the Safety and Efficacy of the VEGFR-FGFR-PDGFR Inhibitor, Lucitanib, Given to Patients With Metastatic Breast Cancer
Official Title  ICMJE A Phase 2, Open-label, Multicenter, Safety and Efficacy Study of Oral Lucitanib in Patients With FGF Aberrant Metastatic Breast Cancer
Brief Summary The purpose of this study is to determine whether lucitanib is safe and effective in the treatment of patients with FGF aberrant metastatic breast cancer, as well as in the treatment of patients with biomarker negative (FGF non-aberrant) metastatic breast cancer.
Detailed Description

Lucitanib is a selective, orally available tyrosine kinase inhibitor targeting FGFR1-3, VEGFR1-3, and PDGFRα and β, with activity in relevant cell lines and animal models.

The first in human trial of lucitanib demonstrated that daily dosing with lucitanib can provide durable clinical responses in patients with FGFR1- or 11q (FGF3, FGF4, Cyclin D1, or FGF19)-amplified breast cancer. RECIST partial responses (PRs) were also observed in patients not known to have FGF abnormalities.

Based on these results, this study is designed to explore the safety and anti-tumor activity of daily lucitanib in breast cancer patients with and without alterations of the FGF pathway.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Breast Cancer
  • Metastatic Breast Cancer
  • MBC
  • HER2 Positive
  • HER2
  • Estrogen Receptor Positive
  • ER
  • Triple Negative
Intervention  ICMJE Drug: Lucitanib
Lucitanib is a potent, orally available selective inhibitor of the tyrosine kinase activity of fibroblast growth factor receptors (FGFR1-3), vascular endothelial growth factor receptors (VEGFR1-3), and platelet-derived growth factor receptors alpha and beta (PDGFR alpha and beta)
Other Name: CO-3810
Study Arms  ICMJE
  • Experimental: Cohort A: Lucitanib (CO-3810) 10 mg daily
    10 mg of lucitanib daily in patients with FGFR1-amplified or 11q-amplified metastatic breast cancer.
    Intervention: Drug: Lucitanib
  • Experimental: Cohort B: Lucitanib (CO-3810) 15 mg daily
    15 mg of lucitanib daily in patients with FGFR1-amplified and 11q-amplified metastatic breast cancer.
    Intervention: Drug: Lucitanib
  • Experimental: Cohort C: Lucitanib (CO-3810) 10 mg daily
    10 mg of lucitanib daily in patients with FGFR1 non-amplified and 11q non-amplified metastatic breast cancer.
    Intervention: Drug: Lucitanib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: April 4, 2016)
178
Original Estimated Enrollment  ICMJE
 (submitted: July 25, 2014)
160
Actual Study Completion Date  ICMJE January 18, 2017
Actual Primary Completion Date January 17, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histologically or cytologically confirmed metastatic breast cancer relapsed or refractory to approved standard available treatment
  • Prior treatment with standard first line therapy in the metastatic setting
  • Availability of tumor tissue sufficient for confirmatory testing of FGFR1 and 11q amplification status
  • Demonstrated progression of disease by radiological or clinical assessment (Measurable disease according to RECIST Version 1.1 is NOT required for enrollment)
  • Estimated life expectancy >6 months

Exclusion Criteria:

  • Current or recent treatment with biologic anticancer therapies
  • Ongoing AEs from prior anticancer therapies
  • Active central nervous system (CNS) metastases
  • Clinically significant or uncontrolled hypertension or cardiac disease
  • Females who are pregnant or breastfeeding
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02202746
Other Study ID Numbers  ICMJE CO-3810-025
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Clovis Oncology, Inc.
Study Sponsor  ICMJE Clovis Oncology, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Clovis Oncology, Inc.
Verification Date June 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP