Non-Small Cell Lung Cancer (NSCLC)Phase 1NCT00821951
Vorinostat in Combination With Palliative Radiotherapy for Patients With Non-Small Cell Lung Cancer
A Phase 1 study testing Vorinostat and Radiotherapy in people with Non-Small Cell Lung Cancer (NSCLC), run by Yale University at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-Small Cell Lung Cancer (NSCLC)
- What is being tested?
- Vorinostat and Radiotherapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 1 siteUnited States
- Study dates
- May 2009to Jul 2012
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Yale University School of Medicine
New Haven, Connecticut, 06520
About this study
Official title: A Dose Escalation Study of Vorinostat in Combination With Palliative Radiotherapy for Patients With Non-Small Cell Lung Cancer
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.
- Conditions
- Non-Small Cell Lung Cancer (NSCLC)
- Being tested
- Vorinostat, Radiotherapy
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VorinostatDrug
Also called SAHA, Hystone Deacetylase (HDAC) inhibitor, ZOLINZA
200 mg, 300 mg, 400 mg, once per RT fraction
RadiotherapyRadiation
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.
| Study group | Role | What they receive |
|---|---|---|
| Vorinostat and Radiotherapy | Experimental | Not described Receives: Drug: Vorinostat; Radiation: Radiotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Primary Endpoint of the Study is to Establish the Maximum Tolerated Dose of Vorinostat When Given Concurrently With Palliative Radiation.
maximum tolerated dose of vorinostat when given concurrently with radiation
Measured: 1 Year
Secondary outcomes (2)
Target Lesion Response
Measured: 1 Year
Vorinostat Modification of the DNA Damage Response in Patient Samples
Measured: 1 Year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jan 2009 (estimated)
- Study startMay 2009
- Primary completionJul 2012
- Study completionJul 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Non-Small Cell Lung Cancer (NSCLC)Studies of the same condition, open and under way.
- More trials run by Yale UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
- Investigators
- Roy Decker, M.D., Ph.D., Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00821951
- Sponsor's protocol ID
- 0811004507
- Status last verified
- Nov 2020
- First submitted
- 8 Jan 2009
- Last updated
- 20 Nov 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Dose Escalation Study of Vorinostat in Combination With Palliative Radiotherapy for Patients With Non-Small Cell Lung Cancer
- ClinicalTrials.gov ID
- NCT00821951
- Acronym / sponsor ID
- 0811004507
- Conditions
- Non-Small Cell Lung Cancer (NSCLC)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- May 2009
- Primary completion
- Jul 2012 (actual)
- Study completion
- Jul 2012 (actual)
- First posted
- 14 Jan 2009 (estimated)
- Results
- Posted 17 Jan 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Vorinostat and Radiotherapy | Experimental | Drug: Vorinostat, Radiation: Radiotherapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- 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.
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VorinostatAlso: SAHA, Hystone Deacetylase (HDAC) inhibitor, ZOLINZA200 mg, 300 mg, 400 mg, once per RT fraction | Drug | Vorinostat and Radiotherapy |
| RadiotherapyStandard 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. | Radiation | Vorinostat and Radiotherapy |
Primary outcome
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
2 secondary outcomes
Target Lesion Response
Time frame: 1 Year
Vorinostat Modification of the DNA Damage Response in Patient Samples
Time frame: 1 Year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Nov 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Roy Decker, M.D., Ph.D. principal investigator
Yale University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Vorinostat and Radiotherapy in people with Non-Small Cell Lung Cancer (NSCLC), run by Yale University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Jan 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Nov 2020.