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

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2015 by Clovis Oncology, Inc.
Sponsor:
Information provided by (Responsible Party):
Clovis Oncology, Inc.
ClinicalTrials.gov Identifier:
NCT02202746
First received: July 25, 2014
Last updated: June 24, 2015
Last verified: June 2015
  Purpose

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.


Condition Intervention Phase
Breast Cancer
Metastatic Breast Cancer
MBC
HER2 Positive
HER2+
Estrogen Receptor Positive
ER+
Triple Negative
Drug: Lucitanib
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2, Randomized, Open-label, Multicenter, Safety and Efficacy Study of Oral Lucitanib in Patients With FGF Aberrant Metastatic Breast Cancer

Resource links provided by NLM:


Further study details as provided by Clovis Oncology, Inc.:

Primary Outcome Measures:
  • Cohorts A and B: Progression-Free Survival (PFS) [ Time Frame: Screening, every 8 weeks; up to 2 years ] [ Designated as safety issue: No ]
    Defined as 1+ the number of days from the date of randomization to disease progression or death due to any cause, whichever occurs first

  • Cohort C: Objective Response Rate (ORR) [ Time Frame: Screening, every 8 weeks; up to 2 years ] [ Designated as safety issue: No ]
    Defined as the best overall response recorded from the start of the treatment until disease progression or recurrence


Secondary Outcome Measures:
  • Cohorts A and B: Objective Response Rate (ORR) [ Time Frame: Screening, every 8 weeks; up to 2 years ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
    Incidence of adverse events (AEs), clinical laboratory abnormalities, and cardiac function, performed on all patients who have received at least one dose of lucitanib

  • Cohort C: Progression-Free Survival (PFS) [ Time Frame: Screening, every 8 weeks; up to 2 years ] [ Designated as safety issue: No ]
    Defined as 1+ the number of days from the date of randomization to disease progression or death due to any cause, whichever occurs first


Estimated Enrollment: 201
Study Start Date: July 2014
Estimated Study Completion Date: November 2016
Estimated Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: Lucitanib
Lucitanib is a potent, orally available selective inhibitor of the tyrosine kinase activity of fibroblast growth factor receptors (FGFR1/2), vascular endothelial growth factor receptors (VEGFR1-3), and platelet-derived growth factor receptors alpha and beta (PDGFR alpha and beta)
Other Name: CO-3810
Experimental: Cohort B: Lucitanib (CO-3810) 15 mg daily
15 mg of lucitanib daily in patients with FGFR1-amplified or 11q-amplified metastatic breast cancer.
Drug: Lucitanib
Lucitanib is a potent, orally available selective inhibitor of the tyrosine kinase activity of fibroblast growth factor receptors (FGFR1/2), vascular endothelial growth factor receptors (VEGFR1-3), and platelet-derived growth factor receptors alpha and beta (PDGFR alpha and beta)
Other Name: CO-3810
Experimental: Cohort C: Lucitanib (CO-3810) 15 mg daily
15 mg of lucitanib daily in patients with FGFR1 non-amplified and 11q non-amplified metastatic breast cancer.
Drug: Lucitanib
Lucitanib is a potent, orally available selective inhibitor of the tyrosine kinase activity of fibroblast growth factor receptors (FGFR1/2), vascular endothelial growth factor receptors (VEGFR1-3), and platelet-derived growth factor receptors alpha and beta (PDGFR alpha and beta)
Other Name: CO-3810

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 15 mg of lucitanib, given daily, can provide durable clinical responses in cancer patients with alterations of the FGF pathway. It has been noted, however, that for many patients, 15 mg daily is difficult to sustain beyond 3 cycles and dose reductions are frequently required. As such, this study will determine whether a starting dose of 10 mg of lucitanib daily is better tolerated and provides similar antitumor activity than 15 mg in patients with FGF aberrant advanced breast cancer, as measured by PFS.

In phase 1, RECIST partial responses (PRs) were also observed in patients not known to have FGF abnormalities. As such, this study will also determine whether 15 mg of lucitanib daily provides antitumor activity in patients with FGF non-aberrant advanced breast cancer, as measured by ORR.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  • For Cohort C (biomarker-negative) patients: Greater than 3 lines of previous chemotherapy in the metastatic setting
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02202746

Contacts
Contact: Clovis Oncology Clinical Trial Navigation Service 1-855-262-3040 (USA) clovistrials@emergingmed.com
Contact: Clovis Oncology Clinical Trial Navigation Service +1-303-625-5160 (ex-USA) clovistrials@emergingmed.com

  Show 32 Study Locations
Sponsors and Collaborators
Clovis Oncology, Inc.
Investigators
Study Director: Jason B Litten, MD Clovis Oncology, Inc.
  More Information

No publications provided

Responsible Party: Clovis Oncology, Inc.
ClinicalTrials.gov Identifier: NCT02202746     History of Changes
Other Study ID Numbers: CO-3810-025
Study First Received: July 25, 2014
Last Updated: June 24, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Clovis Oncology, Inc.:
Breast cancer
Metastatic breast cancer
MBC
HER2 positive
HER2+
Estrogen receptor positive
ER+
Triple negative
FGFR1
11q
FGF aberrant
Biomarker negative
FGF non-aberrant

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Rabeprazole
Anti-Ulcer Agents
Enzyme Inhibitors
Gastrointestinal Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Proton Pump Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on August 02, 2015