Eribulin Mesylate in Combination With Intermittent Erlotinib in Patients With Previously Treated, Advanced Non-Small Cell Lung Cancer
Condition: Non-small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: eribulin mesylate + erlotinib; eribulin mesylate + erlotinib
Intervention description: 21-day Regimen: Eribulin mesylate given at a dose of 2 mg/m2 as a 2-5 min intravenous (IV) bolus on Day 1 and 150 mg of erlotinib given orally once daily, one hour before or two hours after the ingestion of food, on Days 2-16 of a 21-day cycle.; 28-day Regimen: Eribulin mesylate given at a dose of 1.4 mg/m2 as a 2-5 min IV bolus on Days 1 and 8, and 150 mg of erlotinib given orally once daily, one hour before or two hours after the ingestion of food, on Days 15-28 of a 28-day cycle.
Intervention MeSH terms: Erlotinib Hydrochloride
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 123.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: NSCLC; Eribulin Mesylate; Erlotinib

Summary:

      This is a Phase 2, multicenter, randomized study of two different dose regimens of eribulin
      mesylate in combination with intermittent erlotinib in patients with previously treated,
      advanced non-small cell lung cancer.
    

Eligibility criteria:

        Inclusion criteria:

          -  Histologically confirmed non-small cell lung cancer (NSCLC)

          -  At least one prior platinum-based doublet anti-cancer treatment for recurrent or
             advanced NSCLC

          -  Disease progression during or after the last anti-cancer therapy

          -  Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2

          -  Serum creatinine less than or equal to 2.0 mg/dL or creatinine clearance 40 mL/min
             according to Cockcroft and Gault formula:

          -  Absolute neutrophil count greater than or equal to 1.5 x 10^9/L, hemoglobin greater
             than or equal to 10 g/dL (can be corrected by growth factor or transfusion), and
             platelet count greater than or equal to 100 x 10^9/L

          -  Total bilirubin less than or equal to 1.5 times the upper limit of normal (ULN) and
             alkaline phosphatase (AP), alanine aminotransferase (ALT), and aspartate
             aminotransferase (AST) less than or equal to 3 times ULN (in the case of liver
             metastases less than or equal to 5 times ULN). In case AP is greater than 3 times ULN
             (in absence of liver metastases) or greater than 5 times ULN (in presence of liver
             metastases) AND subject also is known to have bone metastases, the liver specific AP
             must be separated from the total and used to assess the liver function instead of the
             total AP.

          -  At least one lesion of greater than or equal to 1.5 cm in longest diameter for
             non-lymph nodes or greater than or equal to 1.5 cm in shortest diameter for lymph
             nodes which is serially measurable according to the Response Evaluation Criteria in
             Solid Tumors (RECIST) version 1.17

               -  Males and females, age greater than or equal to 18 years

               -  Provide written informed consent

               -  Are willing and able to comply with all aspects of the protocol

               -  Females of childbearing potential must have a negative serum beta-human chorionic
                  gonadotropin (Beta-hCG) at Visit 1 (Screening) and a negative urine pregnancy
                  test prior to starting study drug (Visit 2). Female subjects of childbearing
                  potential must agree to be abstinent or to use highly effective methods of
                  contraception (eg, condom + spermicide, condom + diaphragm with spermicide,
                  intrauterine device (IUD), or have a vasectomised partner) having starting for at
                  least one menstrual cycle prior to starting study drugs and throughout the entire
                  study period and for 30 days (longer if appropriate) after the last dose of study
                  drug. Those women using hormonal contraceptives must also be using an additional
                  approved method of contraception (as described previously). Perimenopausal women
                  must be amenorrheic for at least 12 months to be considered of non-childbearing
                  potential.

          -  Male subjects who are not abstinent or have not undergone a successful vasectomy, who
             are partners of women of childbearing potential must use, or their partners must use a
             highly effective method of contraception (eg, condom + spermicide, condom + diaphragm
             with spermicide, IUD) starting for at least one menstrual cycle prior to starting
             study drugs and throughout the entire study period and for 30 days (longer if
             appropriate) after the last dose of study drug. Those with partners using hormonal
             contraceptives must also be using an additional approved method of contraception (as
             described previously).

        Exclusion criteria:

          -  Prior therapy with eribulin or an tyrosine kinase inhibitor of the epidermal growth
             factor receptor

          -  Subjects with brain or subdural metastases are not eligible, unless they have
             completed local therapy and have discontinued steroids for this indication for greater
             than or equal to 4 weeks before starting study treatment. Symptoms attributed to brain
             metastases must be stable for greater than or equal to 4 weeks before starting study
             treatment; radiographic stability should be determined by comparing contrast-enhanced
             computed tomography (CT) or magnetic resonance imaging (MRI) brain scan performed
             during screening to a prior scan performed 4 weeks earlier.

          -  Existing anti-cancer therapy-related toxicities of grade greater than or equal to 2,
             other than any grade of alopecia or grade less than or equal to 2 neuropathy, which
             are acceptable

          -  Current smokers who will not stop smoking one week prior to treatment and during the
             study

          -  History of congestive heart failure with New York Heart Association (NYHA) Grade
             greater than II, unstable angina, myocardial infarction within the past 6 months,
             serious cardiac arrhythmia

          -  Electrocardiogram with QTc interval greater than or equal to 500 msec based upon
             Bazett's formula (QTcB)

          -  Females who are pregnant (positive Beta-hCG test) or breastfeeding

          -  Subject with hypersensitivity to eribulin and /or erlotinib or any of the excipients

          -  Presence of a progressive central nervous system (CNS) disease, including degenerative
             CNS diseases and progressive tumors

          -  Subjects who are known to be human immunodeficiency virus (HIV) positive, because the
             neutropenia caused by the study treatments may make such subjects particularly
             susceptible to infection

          -  Subjects with active viral hepatitis (A, B, or C) as demonstrated by positive serology

          -  Radiotherapy, chemotherapy, biological therapy or investigational agents within 2
             weeks prior to start of study treatment

          -  Meningeal carcinomatosis

          -  History of drug or alcohol dependency or abuse within approximately the last 2 years

          -  Medically unfit to receive the study drug or unsuitable for any other reason according
             to investigator judgment

          -  Any history of or concomitant medical condition that, in the opinion of the
             Investigator, would compromise the subject's ability to safely complete the study

          -  Major surgery within 4 weeks before starting study treatment or scheduled for surgery
             during the projected course of the study