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

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.