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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00821951
Recruitment Status : Completed
First Posted : January 14, 2009
Results First Posted : January 17, 2013
Last Update Posted : November 20, 2020
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Yale University

Brief Summary:
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 or disease Intervention/treatment Phase
Non-Small Cell Lung Cancer (NSCLC) Drug: Vorinostat Radiation: Radiotherapy Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 17 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (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
Study Start Date : May 2009
Actual Primary Completion Date : July 2012
Actual Study Completion Date : July 2012

Resource links provided by the National Library of Medicine

Drug Information available for: Vorinostat

Arm Intervention/treatment
Experimental: Vorinostat and Radiotherapy Drug: Vorinostat
200 mg, 300 mg, 400 mg, once per RT fraction
Other Names:
  • SAHA
  • Hystone Deacetylase (HDAC) inhibitor

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.

Primary Outcome Measures :
  1. 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 ]
    maximum tolerated dose of vorinostat when given concurrently with radiation

Secondary Outcome Measures :
  1. Target Lesion Response [ Time Frame: 1 Year ]
  2. Vorinostat Modification of the DNA Damage Response in Patient Samples [ Time Frame: 1 Year ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00821951

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United States, Connecticut
Yale University School of Medicine
New Haven, Connecticut, United States, 06520
Sponsors and Collaborators
Yale University
Merck Sharp & Dohme Corp.
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Principal Investigator: Roy Decker, M.D., Ph.D. Yale University
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Responsible Party: Yale University Identifier: NCT00821951    
Other Study ID Numbers: 0811004507
First Posted: January 14, 2009    Key Record Dates
Results First Posted: January 17, 2013
Last Update Posted: November 20, 2020
Last Verified: November 2020
Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Antineoplastic Agents
Histone Deacetylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action