Phase I Study of Induction Therapy With VELCADE and Vorinostat in Patients With Surgically Resectable Non-Small Cell Lung Cancer
- Histologically confirmed NSCLC (clinical stage IB, IIA, IIB, IIIA, or selected IIIB
(T4N0-1M0)), exclusive of patients with MPE
- Planned surgical resection
- Age > 18 years
- ECOG performance status 0-1
- Patient has adequate organ and marrow function, as defined below:
- Patient has a platelet count of > 100 x 109/L
- Patient has a WBC count of > 3.5 x 109/L
- Patient has an absolute neutrophil count of > 1.5 x 109/L
- Patient has hemoglobin of > 8 gm/dl. Patients may receive transfusions,
erythropoietin or darbepoetin to achieve this hemoglobin level.
- Patient has a serum creatinine of < 2.0 mg/dL
- Patient has AST < 1.5 x ULN
- Patient has bilirubin < 1.5 x ULN
- Patient has INR < 1.5 x ULN
- Voluntary written informed consent before performance of any study-related procedure
not part of normal medical care, with the understanding that consent may be withdrawn
by the subject at any time without prejudice to future medical care.
- Female subject is either post-menopausal or surgically sterilized or willing to use
an acceptable method of birth control (ie, a hormonal contraceptive, intra-uterine
device, diaphragm with spermicide, condom with spermicide, or abstinence) for the
duration of the study.
- Male subject agrees to use an acceptable method for contraception for the duration of
- Previous chemotherapy or radiation therapy within 5 years before enrollment.
- Prior history of treatment for a known NSCLC within the last 5 years of if > 5 years
but still thought by the investigator to represent recurrent disease.
- Prior exposure to either Velcade or Vorinostat
- Prior exposure to any HDAC inhibitors within the previous 30 days. Patients who have
received such agents for other indications may enroll after 30-day wash-out period.
Subject may not take any other HDAC inhibitor during this trial.
- Patient has >/= Grade 2 peripheral neuropathy within 14 days before enrollment.
- Myocardial infarction within 6 months prior to enrollment or has NYHA Class III or IV
heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or
ECG evidence of acute ischemia or active conduction system abnormalities. Prior to
study entry, any ECG abnormality at Screening has to be documented by the
investigator as not medically relevant.
- Patient has hypersensitivity to VELCADE, boron or mannitol.
- Patient has known allergy to any component of Vorinostat (MK-0683)
- Female subject is pregnant or breast-feeding. Confirm by a negative serum B-hCG
pregnancy test result obtained during screening (not required for post-menopausal or
surgically sterilized women).
- Patient is participating or has participated in another investigational trial, and
has received other investigational drugs/therapies within 30 days of enrollment
- Serious medical or psychiatric illness likely to interfere with participation in this
- Patient has history of GI surgery or other procedures that might, in the opinion of
the investigator, interfere with the absorption or swallowing of the study drugs.
- Subject is currently taking herbal remedy and/or homeopathic agent which cannot (or
the patient is unwilling) be discontinued during the conduct of this trial.