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

NCT02747797 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: 141506
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Advanced Cancer

Keywords

Advanced Cancer; Lucitanib (E3810); Fibroblast Growth Factor Receptor; FGFR; Vascular Endothelial Growth Factor Receptor; VEGFR; Platelet Derived Growth Factor Receptor; PDGFR; metastatic malignancy

Outcome Measures

Primary Outcomes (1)

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

  28-day cycle

Secondary Outcomes (3)

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

  through study completion, up tp 3 years

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

  28-day cycle

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

  28-day cycle

Study Arms (1)

Advanced cancer with lucitanib-targeting biomarker(s)

EXPERIMENTAL

Lucitanib 10 mg orally daily

Drug: Lucitanib

Interventions

Lucitanib DRUG

10 mg orally daily

Also known as: E3810

Advanced cancer with lucitanib-targeting biomarker(s)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Teresa Helsten, MD: lead
• Clovis Oncology, Inc.: collaborator

Study Sites (1)

UC San Diego Moores Cancer Center

La Jolla, California, 92093, United States

Location

MeSH Terms

Conditions

Acrocephalosyndactylia; Neoplasms

Interventions

E-3810; Rabeprazole

Condition Hierarchy (Ancestors)

Craniosynostoses; Synostosis; Dysostoses; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Syndactyly; Craniofacial Abnormalities; Musculoskeletal Abnormalities; Limb Deformities, Congenital; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Teresa Helsten, MD

  University of California, San Diego

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Clinical Professor

Study Record Dates

• First Submitted: March 22, 2016
• First Posted: April 22, 2016
• Study Start: April 1, 2017
• Primary Completion: April 1, 2021
• Study Completion: April 1, 2022
• Last Updated: August 2, 2018

Record last verified: 2018-07

Locations

US (1)