Small Cell Lung CancerPhase 1NCT00958022
Carboplatin and Etoposide Plus LBH589 for Small Cell Lung Cancer
A Phase 1 study testing LBH589 and carboplatin with etoposide in people with Small Cell Lung Cancer, run by Ahmad Tarhini at 1 site in United States.
Trial summary
The subjects are being asked to take part in the Phase I or Phase II portion of a research study of a new investigational drug, LBH589, in combination with chemotherapeutic agents, carboplatin with etoposide. 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?
- LBH589 and carboplatin with etoposide
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2009to Jun 2011
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
None listed.
Who cannot join
- Prior HDAC, DAC, HSP90 inhibitors or valproic acid for the treatment of cancer
- Patients who will need valproic acid for any medical condition during the study or within 5 days prior to first LBH589 treatment
- Impaired cardiac function including any one of the following:
- Screening ECG with a QTc > 450 msec confirmed by treating physician investigator prior to enrollment to the study
- Patients with congenital long QT syndrome
- History of sustained ventricular tachycardia
Show all 24Show fewer
- Any history of ventricular fibrillation or torsades de pointes
- Bradycardia defined as heart rate < 50 beats per minute. Patients with a pacemaker and heart rate ≥ 50 beats per minute are eligible.
- Patients with a myocardial infarction or unstable angina within 6 months of study entry
- Congestive heart failure (NY Heart Association class III or IV)
- Right bundle branch block and left anterior hemiblock (bifascicular block)
- Uncontrolled hypertension. Patients with history of hypertension must be well-controlled (≤140/90) on a stable regimen of anti-hypertensive therapy.
- Concomitant use of drugs with a risk of causing torsades de pointes (See Appendix 1.-1)
- Concomitant use of CYP3A4 inhibitors (See Appendix 1.-2)
- Patients with unresolved diarrhea > CTCAE grade 1
- Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral LBH589
- Other concurrent severe and/or uncontrolled medical conditions
- Patients who have received chemotherapy, any investigational drug or undergone major surgery < 4 weeks prior to starting study drug or who have not recovered from side effects of such therapy.
- Concomitant use of any anti-cancer therapy or radiation therapy.
- Women who are pregnant or breast feeding or women of childbearing potential (WOCBP) not willing to use a double barrier method of contraception during the study and 3 months after the end of treatment. One of these methods of contraception must be a barrier method. WOCBP are defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months (i.e., who has had menses any time in the preceding 12 consecutive months). Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 7 days of the first administration of oral LBH589.
- Male patients whose sexual partners are WOCBP not using a double method of contraception during the study and 3 months after the end of treatment. One of these methods must be a condom
- Patients with known positivity for human immunodeficiency virus (HIV) or hepatitis C; baseline testing for HIV and hepatitis C is not required
- Patients with any significant history of non-compliance to medical regimens or with inability to grant a reliable informed consent.
- Patients with peripheral neuropathy ≥ CTCAE grade 2.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pittsburgh
Pittsburgh, Pennsylvania, 15213
About this study
Official title: Phase I/ II Trial of Carboplatin and Etoposide Plus LBH589 for Previously Untreated Extensive Stage Small Cell Lung Cancer
The subjects are being asked to take part in the Phase I or Phase II portion of a research study of a new investigational drug, LBH589, in combination with chemotherapeutic agents, carboplatin with etoposide. LBH589 (made by Novartis Pharmaceuticals Corp.) is considered "investigational" because it has not been approved for commercial use in the treatment of cancer by the U.S. Food and Drug Administration (FDA). Etoposide and carboplatin are chemotherapeutic agents approved by the FDA for the treatment of for small cell lung cancer.
LBH589 is a drug that may slow down the growth of cancer cells or kill cancer cells by blocking certain enzymes (proteins produced by cells). LBH589 has shown effects against cancer in laboratory studies and in studies using animals; however, it is not known if this medicine will show the same activity in humans. As of May 2006, approximately 100 patients have received treatment with either an intravenous or capsule form of LBH589. Only the capsule form of LBH589 will be used in this study.
Read more
The main goal during the Phase I portion of this research study is to find out the highest and safest dose of LBH589 that can be given in combination with carboplatin with etoposide in subjects with lung cancer without causing severe side effects. The main goal of the Phase II portion of this study is to find how the subject's lung cancer responds to the LBH589 in combination with carboplatin and etoposide at the highest and safest dose that was given in Phase I.
The subject may be enrolled in either Phase I or Phase II of the trial, depending on when they entered the study, but they will not be enrolled in both phases.
This study will also investigate how the subject's body processes the combination of LBH589 and carboplatin with etoposide. To determine this, the investigators will measure the amount of study drug in the subject's blood. This will be done with a series of blood tests, called pharmacokinetic (PK) tests. Pharmacokinetics is the study of how the study drug moves through the body. Other purposes of this study will be to sample the subject's genetic material (DNA/RNA) as well as to determine biomarkers in their blood. (For some cancers, biomarkers are a way to measure the extent of their disease or the effects of treatment.) These samples will also be stored for future studies.
Read the detailed description
Treatment plan
- LBH589 will be given in oral formulation starting at a dose of 10 mg (Dose Level 1) three times per week (doses will be given at least 2 days apart, e.g. Monday, Wednesday, Friday), 2 out of 3 weeks dosing schedule.
- After establishing the MTD of LBH589 at a 2 out 3 weeks dosing schedule, a 3 out of 3 weeks dosing schedule will be tested at that dose, and this schedule will be adopted in the absence of limiting toxicities.
- Carboplatin will be given on day 1, every 21 days, and etoposide on days 1,2,3 every 21 days for up to 6 cycles. LBH589 will be continued weekly, three times-a-week, without interruption after completion of 6 cycles of combination chemotherapy until progression, or intolerable toxicities.
In the phase I part and for cycle 1 only, for the purpose of the PK studies LBH589 will start the week prior to the first carboplatin/etoposide cycle and PD studies will be performed (week -1).
Study design and sample size:
This is a phase I/II study. Phase I: 15-24 patients (estimated; Three to six patients will be enrolled at each dose level); Phase II: 39 patients.
- Conditions
- Small Cell Lung Cancer
- Being tested
- LBH589 and carboplatin with etoposide
- Medical subject headings
- Small Cell Lung Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LBH589 and carboplatin with etoposideDrug
Also called Etoposide: VP-16, VePesid, VP-16-213, EPEG, epipodophyllotoxin, NSC #141540, Carboplatin: Paraplatin, CBDCA, Paraplatin NovaPlus
LBH589 will be given in oral formulation starting at a dose of 10 mg (Dose Level 1) 3x/week (2 days apart, e.g. Mon, Wed, Fri), during 2 weeks out of 3-weekly dosing schedule. After establishing the MTD at a 2 out 3 weeks dosing schedule, a 3 out of 3 weeks dosing schedule will be tested at that dose. This schedule will be adopted in the absence of limiting toxicities. Will be continued weekly after completion of 6 cycles of combo chemotherapy until progression or intolerable toxicities.
Etoposide: Cycles 1-6: 100 mg/m² IV over 60 mins, Days 1-3 every 21 days for 6 cycles Carboplatin: commercially available as a sterile lyophilized powder available in single dose vials containing 50mg, 150mg, or 450mg of carboplatin. Each vial contains equal parts by weight of carboplatin \& mannitol. Commercial supplies will be used for this study. It will be administered as an i.v. infusion over 30 minutes. The dose will be calculated based on patient's body weight at each treatment visit.
| Study group | Role | What they receive |
|---|---|---|
| LBH589 and carboplatin with etoposide | Experimental | The main goal during the Phase I portion of this research study is to find out the highest and safest dose of LBH589 that can be given in combination with carboplatin with etoposide in subjects with lung cancer without causing severe side effects. The main goal of the Phase II portion of this study is to find how lung cancer responds to the LBH589 in combination with carboplatin and etoposide.
This study will also investigate how the body processes the combination of LBH589 and carboplatin with etoposide. Receives: Drug: LBH589 and carboplatin with etoposide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluation of Target Lesions
Measured: 18 weeks
Secondary outcomes (1)
Evaluation of Best Overall Response
Measured: 18 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Aug 2009 (estimated)
- Study startSep 2009
- Primary completionJun 2011
- Study completionJun 2011
Why it stopped: Based on the tolerabilty challenges of the combination
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Small Cell Lung CancerStudies of the same condition, open and under way.
- 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
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ahmad Tarhini
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis Pharmaceuticals
- Responsible party
- Sponsor-investigator, Ahmad Tarhini, University of Pittsburgh
- Investigators
- Ahmad A Tarhini, MD, Principal investigator, UPMC/UPCI
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00958022
- Sponsor's protocol ID
- 08-035
- Status last verified
- Jun 2017
- First submitted
- 10 Aug 2009
- Last updated
- 22 Jun 2017
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 22 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/ II Trial of Carboplatin and Etoposide Plus LBH589 for Previously Untreated Extensive Stage Small Cell Lung Cancer
- ClinicalTrials.gov ID
- NCT00958022
- Acronym / sponsor ID
- 08-035
- Conditions
- Small Cell Lung Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Based on the tolerabilty challenges of the combination
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Ahmad TarhiniUniversity, hospital or other
- Collaborators
- Novartis Pharmaceuticals
- Study start
- Sep 2009
- Primary completion
- Jun 2011 (actual)
- Study completion
- Jun 2011 (actual)
- First posted
- 13 Aug 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The subjects are being asked to take part in the Phase I or Phase II portion of a research study of a new investigational drug, LBH589, in combination with chemotherapeutic agents, carboplatin with etoposide. LBH589 (made by Novartis Pharmaceuticals Corp.) is considered "investigational" because it has not been approved for commercial use in the treatment of cancer by the U.S. Food and Drug Administration (FDA). Etoposide and carboplatin are chemotherapeutic agents approved by the FDA for the treatment of for small cell lung cancer.
LBH589 is a drug that may slow down the growth of cancer cells or kill cancer cells by blocking certain enzymes (proteins produced by cells). LBH589 has shown effects against cancer in laboratory studies and in studies using animals; however, it is not known if this medicine will show the same activity in humans. As of May 2006, approximately 100 patients have received treatment with either an intravenous or capsule form of LBH589. Only the capsule form of LBH589 will be used in this study.
The main goal during the Phase I portion of this research study is to find out the highest and safest dose of LBH589 that can be given in combination with carboplatin with etoposide in subjects with lung cancer without causing severe side effects. The main goal of the Phase II portion of this study is to find how the subject's lung cancer responds to the LBH589 in combination with carboplatin and etoposide at the highest and safest dose that was given in Phase I.
The subject may be enrolled in either Phase I or Phase II of the trial, depending on when they entered the study, but they will not be enrolled in both phases.
This study will also investigate how the subject's body processes the combination of LBH589 and carboplatin with etoposide. To determine this, the investigators will measure the amount of study drug in the subject's blood. This will be done with a series of blood tests, called pharmacokinetic (PK) tests. Pharmacokinetics is the study of how the study drug moves through the body. Other purposes of this study will be to sample the subject's genetic material (DNA/RNA) as well as to determine biomarkers in their blood. (For some cancers, biomarkers are a way to measure the extent of their disease or the effects of treatment.) These samples will also be stored for future studies.
Detailed description
Treatment plan
- LBH589 will be given in oral formulation starting at a dose of 10 mg (Dose Level 1) three times per week (doses will be given at least 2 days apart, e.g. Monday, Wednesday, Friday), 2 out of 3 weeks dosing schedule.
- After establishing the MTD of LBH589 at a 2 out 3 weeks dosing schedule, a 3 out of 3 weeks dosing schedule will be tested at that dose, and this schedule will be adopted in the absence of limiting toxicities.
- Carboplatin will be given on day 1, every 21 days, and etoposide on days 1,2,3 every 21 days for up to 6 cycles. LBH589 will be continued weekly, three times-a-week, without interruption after completion of 6 cycles of combination chemotherapy until progression, or intolerable toxicities.
In the phase I part and for cycle 1 only, for the purpose of the PK studies LBH589 will start the week prior to the first carboplatin/etoposide cycle and PD studies will be performed (week -1).
Study design and sample size:
This is a phase I/II study. Phase I: 15-24 patients (estimated; Three to six patients will be enrolled at each dose level); Phase II: 39 patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| LBH589 and carboplatin with etoposide | Experimental | Drug: LBH589 and carboplatin with etoposideThe main goal during the Phase I portion of this research study is to find out the highest and safest dose of LBH589 that can be given in combination with carboplatin with etoposide in subjects with lung cancer without causing severe side effects. The main goal of the Phase II portion of this study is to find how lung cancer responds to the LBH589 in combination with carboplatin and etoposide. This study will also investigate how the body processes the combination of LBH589 and carboplatin with etoposide. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (24 listed)
- Prior HDAC, DAC, HSP90 inhibitors or valproic acid for the treatment of cancer
- Patients who will need valproic acid for any medical condition during the study or within 5 days prior to first LBH589 treatment
- Impaired cardiac function including any one of the following:
- Uncontrolled hypertension. Patients with history of hypertension must be well-controlled (≤140/90) on a stable regimen of anti-hypertensive therapy.
- Concomitant use of drugs with a risk of causing torsades de pointes (See Appendix 1.-1)
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 |
|---|---|---|
| LBH589 and carboplatin with etoposideAlso: Etoposide: VP-16, VePesid, VP-16-213, EPEG, epipodophyllotoxin, NSC #141540, Carboplatin: Paraplatin, CBDCA, Paraplatin NovaPlusLBH589 will be given in oral formulation starting at a dose of 10 mg (Dose Level 1) 3x/week (2 days apart, e.g. Mon, Wed, Fri), during 2 weeks out of 3-weekly dosing schedule. After establishing the MTD at a 2 out 3 weeks dosing schedule, a 3 out of 3 weeks dosing schedule will be tested at that dose. This schedule will be adopted in the absence of limiting toxicities. Will be continued weekly after completion of 6 cycles of combo chemotherapy until progression or intolerable toxicities. Etoposide: Cycles 1-6: 100 mg/m² IV over 60 mins, Days 1-3 every 21 days for 6 cycles Carboplatin: commercially available as a sterile lyophilized powder available in single dose vials containing 50mg, 150mg, or 450mg of carboplatin. Each vial contains equal parts by weight of carboplatin \& mannitol. Commercial supplies will be used for this study. It will be administered as an i.v. infusion over 30 minutes. The dose will be calculated based on patient's body weight at each treatment visit. | Drug | LBH589 and carboplatin with etoposide |
Primary outcome
Evaluation of Target Lesions
Time frame: 18 weeks
1 secondary outcome
Evaluation of Best Overall Response
Time frame: 18 weeks
Results and safety
The study was stopped early (reason given: Based on the tolerabilty challenges of the combination). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jun 2017.
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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.
Ahmad A Tarhini, MD principal investigator
UPMC/UPCI
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 LBH589 and carboplatin with etoposide in people with Small Cell Lung Cancer, run by Ahmad Tarhini 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 0 inclusion and 24 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 Jun 2017. 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?
The study was stopped early (reason given: Based on the tolerabilty challenges of the combination). Results are not available in the source record.
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?
Evaluation of Target Lesions (time frame: 18 weeks). 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 Jun 2017.