Romidepsin and Erlotinib Hydrochloride in Treating Patients With Stage III or Stage IV Non-Small Cell Lung Cancer
Condition: Lung Cancer; Metastatic Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: Erlotinib plus Romidepsin (8 mg/m^2); Erlotinib plus Romidepsin (10 mg/m^2); Erlotinib plus Romidepsin (10 mg/m^2) + Antiemetic prophylaxis; (Erlotinib plus Romidepsin (8mg/m^2)) + Antiemetic prophylaxis
Intervention MeSH terms: Erlotinib Hydrochloride; Romidepsin; Antiemetics
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 17.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: recurrent non-small cell lung cancer; stage III B non-small cell lung cancer; stage IV non-small cell lung cancer; malignant pleural effusion; adenocarcinoma of the lung; adenosquamous cell lung cancer; bronchoalveolar cell lung cancer; large cell lung cancer; squamous cell lung cancer

Summary:

      RATIONALE: Romidepsin and erlotinib hydrochloride may stop the growth of tumor cells by
      blocking some of the enzymes needed for cell growth.

      PURPOSE: This phase I/II trial is studying the side effects and best dose of romidepsin when
      given together with erlotinib hydrochloride and to see how well they work in treating
      patients with stage III or stage IV non-small cell lung cancer.
    

Eligibility criteria:

        To be eligible for study participation, patients must fulfill all of the following
        criteria:

          -  Histologically confirmed locally advanced or metastatic (stage IIIB pleural effusion
             or stage IV) NSCLC;

          -  Age ≥ 18 years;

          -  Written informed consent;

          -  Measurable disease as defined by Response Evaluation Criteria in Solid Tumors
             (RECIST);

          -  ECOG (Eastern Cooperative Oncology Group ) performance status 0 to 1;

          -  Serum potassium and magnesium greater than or equal to the lower limit of
             institutional normal range (electrolyte abnormalities may be corrected with
             supplementation to meet inclusion criteria);

          -  Negative urine or serum pregnancy test on females of childbearing potential;

          -  All women of childbearing potential must use an effective barrier method of
             contraception (an intrauterine contraceptive device [IUCD] or double barrier method
             using condoms or a diaphragm plus spermicide) during the treatment period and for at
             least 1 month thereafter. Male patients should use a barrier method of contraception
             during the treatment period and for at least 1 month thereafter. Hormonal methods of
             contraception such as the contraceptive pill or patch (particularly those containing
             ethinyl-estradiol) should be avoided due to a potential drug interaction (see Appendix
             D).

          -  Adequate bone marrow, liver, and renal function as evidenced by

          -  Hemoglobin ≥10 g/dL (transfusions and/or erythropoietin-stimulating agents are
             permitted)

          -  Absolute neutrophil count (ANC) ≥1.5 x 109 cells/L • Platelet count ≥100 x 109 cells/L

          -  Total bilirubin <1.5 x upper limit of normal (ULN)

          -  (Aspartate amino transferase) AST/SGOT(serum glutamic-oxaloacetic transaminase) and
             (amino alanine transferase) ALT/SGPT (serum glutamic-pyruvic transaminase) <2.0 x
             upper limit of normal (ULN) or <3.0 x ULN in the presence of demonstrable liver
             metastases

          -  Serum creatinine <2.0 x ULN

          -  Clinically stable brain metastases are permitted

        Phase I study:

          -  Prior erlotinib therapy is permitted (with a 3-week washout period)

          -  Patients may have received prior anti-cancer therapy (with a 3-week washout period)
             or, at the discretion of the investigator, may be treatment-naïve

        Phase II study:

          -  Patients must have received at least one and no more than two prior chemotherapy
             regimens for their advanced NSCLC

          -  Patients may not have received prior erlotinib

        Patients are ineligible for entry if any of the following criteria are met:

          -  Chemotherapy for NSCLC within 3 weeks prior to study entry;

          -  Concomitant use of any other anti-cancer therapy;

          -  Concomitant use of any investigational agent;

          -  Use of any investigational agent within 4 weeks prior to study entry;

          -  Any known cardiac abnormalities such as:

               -  Congenital long QT syndrome;

               -  QTc interval (corrected QT interval) Myocardial infarction within 12 months prior
                  to study entry;

               -  Other significant ECG abnormalities including type II second-degree atrio
                  ventricular (AV) block, third-degree AV block, or bradycardia (ventricular rate <
                  50 beats/min); o A history of coronary artery disease (CAD); eg, angina Canadian
                  Class II-IV. In any patient in whom there is doubt, the patient should have a
                  stress imaging study and, if abnormal, angiography to define whether or not CAD
                  is present;

               -  An ECG recorded at screening showing significant ST depression (ST depression of
                  ≥2 mm, measured from isoelectric line to the ST segment at a point 60 msec from
                  the end of the QRS complex). If there is any doubt, the patient should have a
                  stress imaging study and, if abnormal, angiography to define whether or not CAD
                  is present;

               -  Congestive heart failure (CHF) that meets New York Heart Association (NYHA) Class
                  II to IV definitions and/or ejection fraction < 40% by MUGA ( multiple gated
                  acquisition) scan or <50% by echocardiogram and/or MRI;

               -  A known history of sustained ventricular tachycardia (VT), ventricular
                  fibrillation (VF), Torsades de Pointes, or cardiac arrest unless currently
                  addressed with an automatic implantable cardiac defibrillator (AICD);

               -  Hypertrophic cardiomyopathy or restrictive cardiomyopathy from prior treatment or
                  other causes (if there is any doubt, see ejection fraction criteria above);

               -  Uncontrolled hypertension (defined as blood pressure [BP] ≥160/95; or

               -  Any cardiac arrhythmia requiring anti-arrhythmic medication;

          -  Serum potassium or serum magnesium below lower limit of institutional normal range
             (electrolyte abnormalities may be corrected with supplementation to meet inclusion
             criteria)

          -  Concomitant use of drugs that may cause a prolongation of the QTc interval .

          -  Concomitant use of CYP3A4 inhibitors

          -  Concomitant use of warfarin (due to a potential drug interaction);

          -  Clinically significant active infection (including known infection with human
             immunodeficiency virus [HIV], hepatitis B, or hepatitis C); l >480 milliseconds
             (msec);

          -  Major surgery or radiation within 2 weeks prior to study entry;

          -  Patients who are pregnant or breast-feeding;

          -  Any significant medical or psychiatric condition that might prevent the patient from
             complying with all study procedures;

          -  Prior exposure to romidepsin