Phase I/II Study of Vorinostat and Gefitinib in Relapsed/ or Refractory Patients With Advanced Non-small Cell Carcinoma (NSCLC)
- Histologic or cytologic diagnosis of NSCLC, Stage IV or selected stage IIIB (with
positive pleural effusion or multiple ipsilateral lung nodules) according to the
American Joint Committee on Cancer (AJCC).
- Previously treated with at least one platinum-based chemotherapy.
- Before study entry, a minimum of 28 days must have elapsed since any prior
- Prior radiation therapy is allowed as long as the irradiated area is not the only
source of measurable disease.
- No other forms of cancer therapy, such as radiation, immunotherapy for at least 2
weeks before the enrollment in study.
- Performance status of 0-2 on the ECOG criteria.
- At least one unidimensionally measurable lesion meeting Response Evaluation Criteria
in Solid Tumors (Revised RECIST guideline version 1.1)
- Estimated life expectancy of at least 8 weeks.
- Patient compliance that allow adequate follow-up.
- Adequate hematologic (WBC count 4,000/mm3, platelet count 150,000/mm3), hepatic
(bilirubin level 1.5 mg/dL, AST/ALT 80 IU/L), and renal (creatinine concentration
1.5 mg/dL) function.
- Informed consent from patient or patient's relative.
- Males or females at least 18 years of age.
- If female: childbearing potential either terminated by surgery, radiation, or
menopause, or attenuated by use of an approved contraceptive method (intrauterine
device [IUD], birth control pills, or barrier device) during and for 3 months after
trial. If male, use of an approved contraceptive method during the study and 3
months afterwards. Females with childbearing potential must have a urine negative hCG
test within 7 days prior to the study enrollment.
- Patients with brain metastasis are allowed unless there were clinically significant
neurological symptoms or signs
- Presence of small-cell lung cancer alone or with NSCLC
- Unresolved chronic toxic effects from previous anticancer therapy: but patient could
be enrolled, if they have recovered from any treatment-related toxicities NCI CTCAE
- Inability to swallow tablets
- Second primary malignancy (except in situ carcinoma of the cervix or adequately
treated basal cell carcinoma of the skin or prior malignancy treated more than 5
years ago without recurrence).
- More than three previous chemotherapy regimens for NSCLC
- Previous treatment with any EGFR-TKI
- Patients who have been exposed to any prior HDAC inhibitor, with the exception of
exception of valpronic acid used for treating seizures, provided there is a 30-day
- Patients with active HIV or hepatitis B or C infection
- Concomitant use of phenytoin, carbamazepine, rifampicin, barbiturates, cyclosporine
A, valpronic acid, Phenobarbital, ketoconazole, coumarin-derivative anticoagulants or
St John's wort; severe or uncontrolled systemic disease; clinically active
interstitial lung disease (except uncomplicated lymphangitic carcinomatosis)
pregnancy; and breastfeeding.
- MI within preceding 6 months or symptomatic heart disease, including unstable angina,
congestive heart failure or uncontrolled arrhythmia
- Serious concomitant infection including postobstructive pneumonia
- Major surgery other than biopsy within the past two weeks.