Small Cell Lung CancerPhase 1/2NCT00702962
Carboplatin and Etoposide in Combination With Vorinostat for Patients With Extensive Stage Small Cell Lung Cancer
A Phase 1/2 study testing Vorinostat, Carboplatin, Etoposide in people with Small Cell Lung Cancer, run by Milton S. Hershey Medical Center at 1 site in United States.
Trial summary
The Phase I portion of the study is to assess the maximum tolerated dose of vorinostat when combined with carboplatin plus etoposide. The Phase II portion is to determine progression-free survival among patients with extensive disease small cell lung cancer receiving carboplatin plus etoposide with vorinostat. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Small Cell Lung Cancer
- What is being tested?
- Vorinostat, Carboplatin, Etoposide
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2008to Jul 2012
- Phase
- Phase 1/2
- 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
- Histologically or cytologically confirmed small cell lung cancer.
- Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >20 mm with conventional techniques or as >10 mm with CT scan.
- Patients must be chemotherapy naive.
- Previous radiotherapy is allowed only if < 30% of marrow bearing bones were irradiated and if radiotherapy was completed at least 2 weeks prior to enrollment and the patient has recovered from all adverse effects of prior radiotherapy.
- Age >18 years.
- Life expectancy of greater than 3 months.
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- ECOG performance status <2 (Karnofsky >60%).
- Adequate organ and marrow function.
- Women of childbearing potential and men must agree to use adequate contraception (hormonal or double barrier method of birth control) prior to study entry and for the duration of study participation.
- Ability to understand and the willingness to sign a written informed consent document.
- Both men and women of all races and ethnic groups are eligible for this trial.
Who cannot join
- Patients who have had chemotherapy or any other investigational agent for any indication within 30 days of study enrollment.
- Patients who have had radiotherapy within 2 weeks, prior to entering the study or those who have not recovered from adverse events due to these therapies.
- Patients with known brain metastases are excluded.
- Patients who have been previously treated with an HDAC inhibitor (use of valproic acid is allowed with a 30-day washout).
- Patients with peripheral neuropathy CTC grade >2 are excluded.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
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- Any major surgery within 2 weeks prior to enrollment. Minimally invasive procedures for the purpose of diagnosis or staging of the disease are permitted.
- History of another malignancy in the last 5 years. Patients with prior history of in situ cancer, basal or squamous cell skin cancer are eligible. Patients with other malignancies are eligible if they were cured by surgery alone and have been continuously disease free for at least 5 years.
- Pregnant women are excluded from this study because irinotecan and paclitaxel are antineoplastic agents with 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 agents used in this trial, breastfeeding should be discontinued if the mother is treated with these agents.
- Patients with known HIV, Hepatitis B, Hepatitis C or active Hepatitis A are excluded.
- Patients on any systemic steroids for any indication, with doses that have not been stabilized to the equivalent of < 10 mg/day prednisone during the 30 days prior to study enrollment. This does not include short courses of steroids administered at high doses.
- Patients with the inability to absorb oral vorinostat.
- Patients with known allergy or hypersensitivity to any component of any of the study therapies.
Trial locations and contacts
1 site in 1 country.
United States1 site
Penn State College of Medicine, Penn State Milton S. Hershey Medical Center
Hershey, Pennsylvania, 17033
About this study
Official title: Phase I/II Study of Carboplatin and Etoposide in Combination With Vorinostat for Patients With Extensive Stage Small Cell Lung Cancer
The Phase I portion of the study is to assess the maximum tolerated dose of vorinostat when combined with carboplatin plus etoposide. The Phase II portion is to determine progression-free survival among patients with extensive disease small cell lung cancer receiving carboplatin plus etoposide with vorinostat.
Read the detailed description
Vorinostat inhibits growth and induces apoptosis in various human carcinoma cells. Furthermore, it affects the expression of various genes that are necessary for proliferation of cancer cells. Vorinostat also appears to block angiogenic signaling. Pre-treating four human cancer cell lines (including a brain tumor line) with vorinostat increased the killing efficiency of etoposide, ellipticine, doxorubicin, or cisplatin, but not of the topoisomerase I inhibitor camptothecin 13. Topoisomerase II is a ubiquitous nuclear enzyme that is involved in DNA replication, transcription, chromosome segregation, and apoptosis. It is the target for several anti-cancer drugs including etoposide. Treatment with HDAC inhibitors induces expression of topoisomerase II in cancer cells and enhances the sensitivity to etoposide 14.
Early phase clinical trials have demonstrated single agent anti-cancer activity with vorinostat. In our study, combination of vorinostat with carboplatin and paclitaxel, demonstrated promising anticancer activity against NSCLC, including histological subsets of patients whose tumors demonstrated neuroendocrine differentiation 8. For all these reasons, vorinostat is a rational choice to combine with the regimen of carboplatin and etoposide for evaluation in patients with SCLC-ED.
- Conditions
- Small Cell Lung Cancer
- Being tested
- Vorinostat, Carboplatin, Etoposide
- Keywords
- lung cancer, small cell lung cancer
- Medical subject headings
- Small Cell Lung Carcinoma, Lung Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vorinostat, Carboplatin, EtoposideDrug
Also called Suberoyl anilide hydroxamic acid (SAHA)
Study originally a Phase I standard dose escalation of the study medication Vorinostat with sequential cohorts of 3-6 participants entered to 3 dose levels (200mg, 300mg, 400mg). Dose escalation stopped after participant 1 on dose level 2 due to recently published research identifying an appropriate dosing regimen. A set dose was then to be administered to all subsequent participants. This regimen (a "cycle") consisted of Vorinostat on Day 1 through Day 4, Carboplatin AUC 6 on Day 3, and Etoposide 100 mg/m2 on Day 3 through Day 5. Treatment cycles were repeated every 21 days (3 weeks) for 4 cycles total.
| Study group | Role | What they receive |
|---|---|---|
| Phase I: Vorinostat 200 mg | Experimental | Vorinostat 200 mg PO QD D1-14; Administer with Carbo 6 (AUC) D3; Etoposide 100 mg/m2 D1,2,3 "Vorinostat", "Carboplatin", "Etoposide" Receives: Drug: Vorinostat, Carboplatin, Etoposide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assess Maximum Tolerated Dose of Vorinostat When Combined With Carboplatin and Etoposide of Patients With Extensive Disease SCLC
To estimate the maximum tolerated dose of vorinostat using a traditional dose escalation schedule ("3 + 3 design). MTD is determined by assessing for specific predefined dose limiting toxicities. A starting dose of vorinostat 200mg was combined with carboplatin and etoposide. Dose escalation went in increments of 100mg (i.e. 300mg, 400mg).
Measured: 2 years, not analyzed
Secondary outcomes (3)
To Evaluate Overall Survival of Patients With Extensive Disease SCLC Receiving Carboplatin, Etoposide, and a Fixed Dose (300mg) of Vorinostat
For the purpose of this study, overall survival is defined as the percentage of participants who are alive at two years post initiation of study treatment.
Measured: 2 years, not analyzed
Evaluate Objective Response Rate Among Patients With Extensive Disease SCLC Receiving Carboplatin and Etoposide With a Fixed Dose of Vorinostat.
Eligibility limits the study population to those who have measurable disease pre-treatment. This secondary outcome measure was intended to objectively evaluate disease response and survival rate in recipients of the investigational medication regimen. Disease response was performed using standard diagnostic imaging. Tumor markers and cytology may be used to support the imaging results. Objective response rate was defined as progression-free survival (PFS) among treatment recipients. PFS, is defined as time (in months) from entry to clinical evidence of disease progression or death without progression. The clinical trial closed prematurely due to low accrual. For this reason, an analysis of this secondary objective would not be meaningful. No analysis done.
Measured: 2 years, not analyzed
To Assess the Safety Profile and Define the Toxicities of Using a Fixed Dose (300mg) of Vorinostat With Carboplatin and Etoposide
Evaluation of resultant adverse events that occurred with participants with extensive disease SCLC after initiating treatment using a fixed dose of vorinostat in combination with carboplatin and etoposide.
Measured: 2 years, not analyzed
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jun 2008 (estimated)
- Study startSep 2008
- Primary completionJul 2012
- Study completionJul 2012
Why it stopped: Poor accrual
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 Small Cell Lung CancerStudies of the same condition, open and under way.
- More trials run by Milton S. Hershey Medical CenterThe 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 1/2
- Primary purpose
- Treatment
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Milton S. Hershey Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC, University of Pennsylvania
- Responsible party
- Principal investigator, Chandra P. Belani, Milton S. Hershey Medical Center
- Investigators
- Chandra P Belani, MD, Principal investigator, Penn State College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00702962
- Sponsor's protocol ID
- PSHCI 08-005
- Status last verified
- Sep 2018
- First submitted
- 19 Jun 2008
- Last updated
- 22 Oct 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided: To determine if data is valuable
Study at a glance
From the registry record, last updated by the sponsor on 22 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Study of Carboplatin and Etoposide in Combination With Vorinostat for Patients With Extensive Stage Small Cell Lung Cancer
- ClinicalTrials.gov ID
- NCT00702962
- Acronym / sponsor ID
- PSHCI 08-005
- Conditions
- Small Cell Lung Cancer
- Keywords
- lung cancer, small cell lung cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Poor accrual
- Enrolment
- 8 participants (actual)
- Lead sponsor
- Milton S. Hershey Medical CenterUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC, University of Pennsylvania
- Study start
- Sep 2008 (actual)
- Primary completion
- Jul 2012 (actual)
- Study completion
- Jul 2012 (actual)
- First posted
- 20 Jun 2008 (estimated)
- Results
- Posted 15 Oct 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The Phase I portion of the study is to assess the maximum tolerated dose of vorinostat when combined with carboplatin plus etoposide. The Phase II portion is to determine progression-free survival among patients with extensive disease small cell lung cancer receiving carboplatin plus etoposide with vorinostat.
Detailed description
Vorinostat inhibits growth and induces apoptosis in various human carcinoma cells. Furthermore, it affects the expression of various genes that are necessary for proliferation of cancer cells. Vorinostat also appears to block angiogenic signaling. Pre-treating four human cancer cell lines (including a brain tumor line) with vorinostat increased the killing efficiency of etoposide, ellipticine, doxorubicin, or cisplatin, but not of the topoisomerase I inhibitor camptothecin 13. Topoisomerase II is a ubiquitous nuclear enzyme that is involved in DNA replication, transcription, chromosome segregation, and apoptosis. It is the target for several anti-cancer drugs including etoposide. Treatment with HDAC inhibitors induces expression of topoisomerase II in cancer cells and enhances the sensitivity to etoposide 14.
Early phase clinical trials have demonstrated single agent anti-cancer activity with vorinostat. In our study, combination of vorinostat with carboplatin and paclitaxel, demonstrated promising anticancer activity against NSCLC, including histological subsets of patients whose tumors demonstrated neuroendocrine differentiation 8. For all these reasons, vorinostat is a rational choice to combine with the regimen of carboplatin and etoposide for evaluation in patients with SCLC-ED.
Study design
- Primary purpose
- Treatment
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Phase I: Vorinostat 200 mg | Experimental | Drug: Vorinostat, Carboplatin, EtoposideVorinostat 200 mg PO QD D1-14; Administer with Carbo 6 (AUC) D3; Etoposide 100 mg/m2 D1,2,3 "Vorinostat", "Carboplatin", "Etoposide" |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Histologically or cytologically confirmed small cell lung cancer.
- Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >20 mm with conventional techniques or as >10 mm with CT scan.
- Patients must be chemotherapy naive.
- Previous radiotherapy is allowed only if < 30% of marrow bearing bones were irradiated and if radiotherapy was completed at least 2 weeks prior to enrollment and the patient has recovered from all adverse effects of prior radiotherapy.
- Age >18 years.
Key exclusion criteria (13 listed)
- Patients who have had chemotherapy or any other investigational agent for any indication within 30 days of study enrollment.
- Patients who have had radiotherapy within 2 weeks, prior to entering the study or those who have not recovered from adverse events due to these therapies.
- Patients with known brain metastases are excluded.
- Patients who have been previously treated with an HDAC inhibitor (use of valproic acid is allowed with a 30-day washout).
- Patients with peripheral neuropathy CTC grade >2 are excluded.
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 |
|---|---|---|
| Vorinostat, Carboplatin, EtoposideAlso: Suberoyl anilide hydroxamic acid (SAHA)Study originally a Phase I standard dose escalation of the study medication Vorinostat with sequential cohorts of 3-6 participants entered to 3 dose levels (200mg, 300mg, 400mg). Dose escalation stopped after participant 1 on dose level 2 due to recently published research identifying an appropriate dosing regimen. A set dose was then to be administered to all subsequent participants. This regimen (a "cycle") consisted of Vorinostat on Day 1 through Day 4, Carboplatin AUC 6 on Day 3, and Etoposide 100 mg/m2 on Day 3 through Day 5. Treatment cycles were repeated every 21 days (3 weeks) for 4 cycles total. | Drug | Phase I: Vorinostat 200 mg |
Primary outcome
Assess Maximum Tolerated Dose of Vorinostat When Combined With Carboplatin and Etoposide of Patients With Extensive Disease SCLC
Time frame: 2 years, not analyzed
To estimate the maximum tolerated dose of vorinostat using a traditional dose escalation schedule ("3 + 3 design). MTD is determined by assessing for specific predefined dose limiting toxicities. A starting dose of vorinostat 200mg was combined with carboplatin and etoposide. Dose escalation went in increments of 100mg (i.e. 300mg, 400mg).
3 secondary outcomes
To Evaluate Overall Survival of Patients With Extensive Disease SCLC Receiving Carboplatin, Etoposide, and a Fixed Dose (300mg) of Vorinostat
Time frame: 2 years, not analyzed
Evaluate Objective Response Rate Among Patients With Extensive Disease SCLC Receiving Carboplatin and Etoposide With a Fixed Dose of Vorinostat.
Time frame: 2 years, not analyzed
To Assess the Safety Profile and Define the Toxicities of Using a Fixed Dose (300mg) of Vorinostat With Carboplatin and Etoposide
Time frame: 2 years, not analyzed
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Oct 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Undecided. To determine if data is valuable
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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.
Chandra P Belani, MD principal investigator
Penn State College of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Vorinostat, Carboplatin, Etoposide in people with Small Cell Lung Cancer, run by Milton S. Hershey Medical Center 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 11 inclusion and 13 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: stopped early, as of the sponsor's last update on 22 Oct 2018. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 15 Oct 2018). 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?
Assess Maximum Tolerated Dose of Vorinostat When Combined With Carboplatin and Etoposide of Patients With Extensive Disease SCLC (time frame: 2 years, not analyzed). 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 22 Oct 2018.