Study of Vorinostat and Gefitinib in Relapsed/ or Refractory Patients With Advanced Non-small Cell Carcinoma (NSCLC)

NCT01027676 | Unknown Phase 1

• 1 other identifier: NCCCTS-09-433
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

Gefitinib is an orally active epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) and produces 8-20% of response rates in patients with advanced non-small cell lung cancer (NSCLC). Vorinostat (suberoylanilide hydroxamic acid \[SAHA\]) is a small-molecule inhibitor of histone deacetylase (HDAC) and induces cell differentiation, cell cycle arrest, and apoptosis in several tumor cells. There is a strong synergistic antiproliferative effect of vorinostat in combination with gefitinib in NSCLC cells. Vorinostat increases expression of E-cadherin and ErbB-3, which results in increased sensitivity to gefitinib. Moreover, In-vitro studies have shown that vorinostat leads to acetylation and disruption of Hsp90, which may lead to decreases in activity of pro-growth and prosurvival client proteins (J Bio Chem 2005;280:26729, Br J Cancer 2006;95:S2). These findings suggest that combination of vorinostat with gefitinib may improve the efficacy of gefitinib in NSCLC.

Conditions

Non-Small-Cell Lung Carcinoma

Keywords

Gefitinib; Vorinostat

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival

  The first day of treatment to the date that disease progression is reported or death date

  every 8 weeks

Secondary Outcomes (2)

• Overall Survival

  every 8 weeks

• Objective Response rate

  every 8 weeks

Study Arms (1)

study arm

EXPERIMENTAL

single arm Gefitinib plus vorinostat

Drug: Study treatment

Interventions

Study treatment DRUG

Gefitinib 250mg/QD plus vorinostat D1\~7 \& D15-21 / QD q 4weeks

study arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 chemotherapy.
• 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

You may not qualify if:

• 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 grade ≤2
• 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 washout period
• 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.

Sponsors & Collaborators

• National Cancer Center, Korea: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

National Cancer Center

Goyang-si, Gyeonggi-do, 410-769, South Korea

Location

Related Publications (1)

• Han JY, Lee SH, Lee GK, Yun T, Lee YJ, Hwang KH, Kim JY, Kim HT. Phase I/II study of gefitinib (Iressa((R))) and vorinostat (IVORI) in previously treated patients with advanced non-small cell lung cancer. Cancer Chemother Pharmacol. 2015 Mar;75(3):475-83. doi: 10.1007/s00280-014-2664-9. Epub 2015 Jan 1.

  PMID: 25552401 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Pharmaceutical Preparations

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• JI-YOUN HAN, M.D.

  National Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head, Center for Lung Cancer

Study Record Dates

• First Submitted: December 8, 2009
• First Posted: December 9, 2009
• Study Start: June 1, 2010
• Primary Completion: December 1, 2013
• Study Completion: March 1, 2014
• Last Updated: November 14, 2013

Record last verified: 2013-11

Locations

KR (1)