Vorinostat in Combination With Palliative Radiotherapy for Patients With Non-Small Cell Lung Cancer

This study has been completed.
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Yale University
ClinicalTrials.gov Identifier:
NCT00821951
First received: January 8, 2009
Last updated: December 7, 2012
Last verified: December 2012
  Purpose

This is a dose escalation study that will assess the safety of Vorinostat, a Histone Deacetylase (HDAC) inhibitor, in combination with palliative radiotherapy in patients with advanced or metastatic Non-Small Cell Lung Cancer (NSCLC). Vorinostat has been approved for use in patients with cutaneous T-cell lymphomas, but several pre-clinical studies suggest activity in lung cancer cell lines. Several HDAC inhibitors,including Vorinostat, may enhance the effect of radiotherapy, and this study will seek to confirm this.


Condition Intervention Phase
Non-Small Cell Lung Cancer (NSCLC)
Drug: Vorinostat
Radiation: Radiotherapy
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Dose Escalation Study of Vorinostat in Combination With Palliative Radiotherapy for Patients With Non-Small Cell Lung Cancer

Resource links provided by NLM:


Further study details as provided by Yale University:

Primary Outcome Measures:
  • The Primary Endpoint of the Study is to Establish the Maximum Tolerated Dose of Vorinostat When Given Concurrently With Palliative Radiation. [ Time Frame: 1 Year ] [ Designated as safety issue: Yes ]
    maximum tolerated dose of vorinostat when given concurrently with radiation


Secondary Outcome Measures:
  • Target Lesion Response [ Time Frame: 1 Year ] [ Designated as safety issue: No ]
  • Vorinostat Modification of the DNA Damage Response in Patient Samples [ Time Frame: 1 Year ] [ Designated as safety issue: No ]

Enrollment: 17
Study Start Date: May 2009
Study Completion Date: July 2012
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Vorinostat and Radiotherapy Drug: Vorinostat
200 mg, 300 mg, 400 mg, once per RT fraction
Other Names:
  • SAHA
  • Hystone Deacetylase (HDAC) inhibitor
  • ZOLINZA
Radiation: Radiotherapy
Standard fractionation of 3.0 Gy per day over 2 weeks, to a total dose of 30 Gy, will be utilized for all patients. All patients will be treated one time per day, 5 days per week unless interruption is clinically indicated.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Eligibility Criteria
  • Patients must have histologically or cytologically confirmed NSCLC. Patients must have metastatic disease, stage IIIB with malignant pleural effusion, or be otherwise unsuitable for potentially curative therapy due to bulk of disease or comorbid medical illness. There must be disease apparent on imaging which offers a medical indication for radiation therapy. Palliative radiotherapy would be offered as appropriate standard therapy outside of a study setting. (NOTE: Radiotherapy utilized in this regimen is the same as that which would be offered as standard treatment outside of this study). Indications for palliative radiation include pain, pathologic fracture or risk of fracture, lymphovascular obstruction, bronchial obstruction, neural impingement, dyspnea, or bleeding.
  • There must be a measurable tumor target (visible, palpable, or radiographically evident) for palliative radiation. The target for radiotherapy must be in the thoracic region (i.e., there must be normal lung tissue at the same anatomic level).
  • Previous systemic therapy for NSCLC is allowed, as long as all prior therapy was completed at least two weeks before enrollment. Patients treated with nitrosurea or radioisotope may not be enrolled unless such treatment was at least 6 weeks prior to enrollment. Patients must have no previous exposed to HDAC inhibitors (patients previously treated with valproic acid are eligible if the exposure was greater than 30 days prior to enrollment).
  • Age ≥18 years. Because no dosing or adverse event data are currently available on the use of vorinostat alone, or in combination radiation in patients <18 years of age, children are excluded from this study.
  • ECOG performance status ≤3
  • Life expectancy of greater 3 months.
  • Patients must have normal organ and marrow function as defined below, all laboratory values to be obtained within 2 weeks prior to enrollment:
  • absolute neutrophil count ≥1,500/mcL
  • platelets ≥100,000/mcL
  • hemoglobin ≥9 g/ dL
  • serum bilirubin <1.5 times the upper limit of normal (ULN) serum AST, ALT, ALP <2.5 times ULN
  • serum Creatinine <1.5 times ULN
  • serum Potassium, Magnesium, Calcium - within normal range
  • The effects of radiation on the developing human fetus are known to be teratogenic. For this reason, women of child-bearing potential and sexually active men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
  • Ability to understand and the willingness to sign a written informed consent document.
  • Ability to swallow a capsule
  • Patients must have had a CT scan of the chest, abdomen, and pelvis (or PET/CT of the body), as well as an MRI or contrasted CT of the brain within 30 days of enrollment

Exclusion Criteria:

  • Patients with known, untreated brain metastases will be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. Patients who have received whole brain radiotherapy within 2 weeks of enrollment will also be excluded.
  • Patients treated on an investigational drug trial within 30 days of study enrollment.
  • Patients with active grade 2 or greater acute toxicity related to prior cancer-directed therapy
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to vorinostat, or patients with a history of an unanticipated severe normal tissue reaction to previous radiation treatment.
  • Patients with congenital long QT-syndrome will be excluded, as a known side effect of vorinostat is prolongation of QT interval. Patients on anti-arrhythmic medications or other medications known to lead to prolonged QT interval will be exclude unless an ECG has been obtained documenting a normal QT interval within 90 days prior to enrollment.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection (fever >38ºC within 48 hours of enrollment), symptomatic congestive heart failure (i.e., NYHA class 3 or greater), unstable angina pectoris, coronary angioplasty within 6 months prior to enrollment, or cardiac arrhythmia. Additionally, patients with suspected or confirmed poor compliance, mental instability, or prior or current alcohol or drug abuse deemed by the investigator to be likely to affect their ability to sign the informed consent, or undergo study procedures will be excluded.
  • Pregnant women are excluded from this study because radiation has the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with vorinostat, breastfeeding should be discontinued if the mother is treated. Women of childbearing potential must have a negative pregnancy test prior to enrollment.
  • Patients with active HIV or viral hepatitis.
  • Patients in whom primary radiation therapy, with potentially curative intent, is indicated will be excluded.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00821951

Locations
United States, Connecticut
Yale University School of Medicine
New Haven, Connecticut, United States, 06520
Sponsors and Collaborators
Yale University
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: Roy Decker, M.D., Ph.D. Yale University
  More Information

No publications provided

Responsible Party: Yale University
ClinicalTrials.gov Identifier: NCT00821951     History of Changes
Other Study ID Numbers: 0811004507
Study First Received: January 8, 2009
Results First Received: December 7, 2012
Last Updated: December 7, 2012
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Vorinostat
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Histone Deacetylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 16, 2014