Clinical Trials /

Lucitanib (E3810) in Patients With Advanced Cancer and FGFR, VEGFR, or PDGFR Pathway Aberrations

NCT02747797

Description:

Lucitanib is an oral multi kinase inhibitor designed to block the action of certain molecules called "angiogenic factors" that may cause tumors to grow. These factors are called vascular endothelial growth factor (VEGF), platelet derived growth factor receptor (PDGFR) and fibroblast growth factor (FGF). Lucitanib is experimental and not approved by the FDA for the treatment of cancer. The purpose of this study is to look at the effects of lucitanib in cancer patients whose cancers harbor aberrations in FGFR, VEGFR, PDGFR or other markers predicted to be sensitive to lucitanib. This study will also look for biomarkers in samples of blood and tumor tissue to identify patients most likely to respond to lucitanib. Biomarkers are substances such as genetic material (DNA and RNA) and proteins found in blood and tumor tissue that might show if a cancer patient will respond or not respond to a drug.

Related Conditions:
  • Cancer
Recruiting Status:

Withdrawn

Phase:

Phase 2

Trial Eligibility

Document

<span class="go-doc-concept go-doc-intervention">Lucitanib</span> (E3810) in Patients With Advanced Cancer and <span class="go-doc-concept go-doc-biomarker">FGFR</span>, <span class="go-doc-concept go-doc-biomarker">VEGFR</span>, or <span class="go-doc-concept go-doc-biomarker">PDGFR</span> Pathway Aberrations

Title

  • Brief Title: Lucitanib (E3810) in Patients With Advanced Cancer and FGFR, VEGFR, or PDGFR Pathway Aberrations
  • Official Title: Histology-Independent Study of the Multikinase Inhibitor Lucitanib (E3810) in Patients With Advanced Cancer and Fibroblast Growth Factor Receptor (FGFR), Vascular Endothelial Growth Factor Receptors (VEGFR), or Platelet Derived Growth Factor Receptor (PDGFR) Pathway Aberrations
  • Clinical Trial IDs

    NCT ID: NCT02747797

    ORG ID: 141506

    Trial Conditions

    Advanced Cancer

    Trial Interventions

    Drug Synonyms Arms
    Lucitanib E3810 Advanced cancer with lucitanib-targeting biomarker(s)

    Trial Purpose

    Lucitanib is an oral multi kinase inhibitor designed to block the action of certain
    molecules called "angiogenic factors" that may cause tumors to grow. These factors are
    called vascular endothelial growth factor (VEGF), platelet derived growth factor receptor
    (PDGFR) and fibroblast growth factor (FGF). Lucitanib is experimental and not approved by
    the FDA for the treatment of cancer.

    The purpose of this study is to look at the effects of lucitanib in cancer patients whose
    cancers harbor aberrations in FGFR, VEGFR, PDGFR or other markers predicted to be sensitive
    to lucitanib. This study will also look for biomarkers in samples of blood and tumor tissue
    to identify patients most likely to respond to lucitanib. Biomarkers are substances such as
    genetic material (DNA and RNA) and proteins found in blood and tumor tissue that might show
    if a cancer patient will respond or not respond to a drug.

    Detailed Description

    Lucitanib is an oral multi kinase inhibitor designed to block the action of certain
    molecules called "angiogenic factors" that may cause tumors to grow. These factors are
    called vascular endothelial growth factor (called VEGF), platelet derived growth factor
    receptor (PDGFR) and fibroblast growth factor (called FGF). Lucitanib is experimental and
    not approved by the FDA for the treatment of cancer.

    The purpose of this clinical trial is to study the following in cancer patients whose
    cancers harbor aberrations in FGFR, VEGFR, PDGFR, or other biomarkers predicted to be
    sensitive to lucitanib:

    - To look at the effects of lucitanib on their disease at 10 mg once daily.

    - To look for biomarkers in samples of blood and tumor tissue to identify patients most
    likely to respond to lucitanib.

    - To look at the safety of lucitanib in these patients

    This is a two-center, open-label, non-randomized Phase II study of lucitanib in adult
    subjects with advanced cancers. Treatment will consist of daily oral administration of 10mg
    of lucitanib in 28-day cycles.

    All patients providing informed consent will be screened for eligibility. Baseline
    assessments will include vital signs, physical exam, blood hematology and chemistries, ECG,
    and ECHO. If not done within the prior 4 weeks, a PET/CT scan, MRI, and/or CT scan will be
    performed for radiological evaluation of disease.

    Clinical evaluations include physical exam, vitals, ECG (obtained once every month
    throughout treatment); blood hematology and chemistries (obtained every two weeks for the
    first three months and then once every month throughout treatment); radiologic evaluations
    (PET/CT, CT and/or MRI, +/- bone imaging as clinically appropriate) will be performed every
    8 weeks.

    This study may last up to approximately 4 years or longer, depending on whether or not the
    study doctor feels that continuing lucitanib dosing is in the patient's best interest. Once
    a patient finishes study treatment with lucitanib, patients will need to complete an End of
    Study visit. Each of the study visits can last from approximately 2 to 8 hours.

    Trial Arms

    Name Type Description Interventions
    Advanced cancer with lucitanib-targeting biomarker(s) Experimental Lucitanib 10 mg orally daily Lucitanib

    Eligibility Criteria

    Inclusion Criteria:

    - Pathologically confirmed advanced or metastatic malignancy characterized by one or
    more of the following:

    - Subject is intolerant of standard therapy

    - Malignancy is refractory to standard therapy

    - Malignancy relapsed after standard therapy

    - Malignancy for which there is no standard therapy that improves survival by at
    least 3 months.

    - Subjects must have evaluable tumor(s) with documented alteration(s) in potential
    lucitanib related biomarker(s) VEGFR, FGFR, PDGFR.

    - Laboratory function within specified parameters:

    - Adequate bone marrow function: absolute neutrophil count 1,500/mL; hemoglobin
    8.5 g/dL, platelets 75,000/mL.

    - Adequate liver function: transaminases (AST/ALT) and alkaline phosphatase 3 (
    5 X ULN in the setting of liver metastasis) x ULN; bilirubin 1.5 x ULN.

    - Adequate renal function: creatinine clearance 40 mL/min (Cockcroft Gault).

    - Adequate blood coagulation: international normalized ratio (INR) 2.3.

    - Serum amylase and lipase 1.5 x ULN.

    - Adequately controlled blood pressure (BP): BP 150/90 mm Hg. Use of > 2
    antihypertensive agents at enrollment is not allowed.

    - Adequate performance status: Eastern Cooperative Oncology Group (ECOG) 0-2

    - Subjects must be off other anti-tumor agents for at least 5 half lives of the agent
    or 4 weeks from the last day of treatment, whichever is shorter. Endocrine therapies
    (e.g., for breast or prostate cancer) and anti-Her2 therapies (for example,
    trastuzumab, pertuzumab, or lapatinib) are allowed to continue while on this study.
    Bisphosphonates or denosumab are allowed for subjects with bone metastasis.

    - Subjects may not be receiving any other experimental agents or agents that are not
    FDA approved.

    Exclusion Criteria:

    - Pregnant or lactating women.

    - Uncontrolled hypertension (defined as SBP 140 mmHg and/or DBP 90 mmHg with
    optimized antihypertensive therapy)

    - Subjects who have not recovered from toxicities as a result of prior anticancer
    therapy, except alopecia and infertility. Recovery is defined as < Grade 2 severity
    per Common Terminology Criteria for Adverse Events Version 4.3.

    - Significant cardiovascular impairment: history of CHF greater than New York Heart
    Association (NYHA) Class II, unstable angina, MI or stroke within 6 months of the
    first dose of study drug, or cardiac arrhythmia requiring medical treatment.

    - Uncontrolled hypothyroidism defined as serum TSH higher than 5 mIU/mL while receiving
    appropriate thyroid hormone therapy.

    - Bleeding or thrombotic disorders or use of anticoagulants requiring therapeutic INR
    monitoring, e.g., warfarin or similar agents. Treatment with LMWH and factor X
    inhibitors that do not require INR monitoring is permitted. Anti-platelet agents are
    prohibited throughout the study.

    - Current treatment with any prohibited medications associated with prolongation of QT
    interval.

    - Received strong inhibitors of CYP2C8 or CYP3A4 or strong inducers of CYP3A4 7 days
    prior to first dose of lucitanib or have on-going requirements for these medications.

    - Received bevacizumab < 3 months prior to first dose of lucitanib.

    - Major surgery (not including placement of central lines) within 3 weeks prior to
    study or planned surgery during the course of this study.

    - Subjects with breast or lung cancer who are eligible for other clinical trials of
    lucitanib open at their institution are not eligible for this trial.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Response rates to lucitanib in subjects with advanced cancers harboring aberrations targeted by lucitanib.

    Secondary Outcome Measures

    Clinical Benefit rates (complete response (CR), partial response (PR), or stable disease (SD) 6 months) in the study population.

    Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

    Correlation between response rates and specific molecular tumor profile (type of FGF/FGFR or other aberration) in a descriptive fashion

    Trial Keywords

    Advanced Cancer

    Lucitanib (E3810)

    Fibroblast Growth Factor Receptor

    FGFR

    Vascular Endothelial Growth Factor Receptor

    VEGFR

    Platelet Derived Growth Factor Receptor

    PDGFR

    metastatic malignancy