Carcinoma NeuroendocrinePhase 1NCT00926640
A Phase I Study of Belinostat in Combination With Cisplatin and Etoposide in Adults With Small Cell Lung Carcinoma and Other Advanced Cancers
A Phase 1 study testing Belinostat, Cisplatin and Etoposide in people with Carcinoma Neuroendocrine and Small Cell Lung Carcinoma, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
BACKGROUND: The histone deacetylase (HDAC) inhibitors are a novel class of anticancer agent. These agents lead to the increased acetylation of both histone and non-histone proteins, which leads to rapid cell death in many tumor models. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Carcinoma Neuroendocrine, Small Cell Lung Carcinoma, Malignant Epithelial Neoplasms
- What is being tested?
- Belinostat, Cisplatin and Etoposide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jul 2009to 20 Apr 2018
- 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 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- Patients who have not recovered (CTCAE less than or equal to grade 1) from adverse events due to prior treatments, except for alopecia or base stable grade 2 tinnitus (not interfering with ADL s) or stable grade 2 sensory neuropathy without pain or motor component, and not interfering with ADL s.
- Patients may not have received more than 2 prior cytotoxic regimens.
- Patients may not be receiving any other investigational agent with therapeutic anticancer intent.
- Patients may not have taken another histone deacetylase inhibitor (i.e. valproic acid, vorinostat) for at least 2 weeks prior to enrollment.
- Patients with history of CNS metastasis may not be enrolled on the study, unless control has been achieved with either radiation or surgical resection at least 3 months prior to enrollment on study.
- Patients who have had radiation to the pelvis or other bone marrow-bearing sites will be considered on a case by case basis and may be excluded if the bone marrow reserve is not considered adequate (>25% of bone marrow).
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- Uncontrolled medical illness including, but not limited to ongoing or active infection, chronic or acute hepatitis, renal failure, symptomatic congestive heart failure, myocardial infarction unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- HIV-positive patients.
- Patients with acute or chronic hepatitis.
- Pregnant patients may not receive this experimental therapy.
- Significant cardiovascular disease, myocardial infarction within the past 6 months, unstable angina, unstable arrhythmia or a need for anti-arrhythmic therapy (use of medication to control heart rate in patients with atrial fibrillation is allowed, if stable medication for at least last month prior to randomization and medication not listed as causing Torsade de Points), or evidence of acute ischemia on ECG.
- Baseline prolongation of QT/QTc interval, i.e., defined as an average QTc interval > 450 msec; Long QT Syndrome; or the required use of concomitant medication that may cause Torsade de Pointes.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: A Phase I Study of Belinostat in Combination With Cisplatin and Etoposide in Adults With a Focus on Small Cell Lung Cancer and Other Cancers of Neuroendocrine Origin
BACKGROUND:
- The histone deacetylase (HDAC) inhibitors are a novel class of anticancer agent. These agents lead to the increased acetylation of both histone and non-histone proteins, which leads to rapid cell death in many tumor models. It is thought that the cell death observed with this class of agents may be mediated, in part, through the selective acetylation of histone proteins resulting in increased expression of specific genes.
- For solid tumors in general, cell death in preclinical models has not translated to activity in patients. For this reason, studies increasingly have combined chemotherapy with HDAC inhibitors to achieve additive and potentially synergistic effects on cancer cells.
- This protocol will study a continuous infusion of the HDAC inhibitor belinostat in combination with cisplatin and etoposide for patients with advanced cancer.
Read more
OBJECTIVES:
- To determine a safe and tolerable phase 2 dose for the combination of belinostat with cisplatin and etoposide.
- Evaluate molecular markers of HDAC inhibition.
ELIGIBILITY:
- The protocol will be open to all patients with recurrent or advanced cancer (small-cell lung cancer and other advanced cancers) for whom standard therapy offers no curative potential.
- Age greater than or equal to 18 years
- ECOG Performance Status 0-2
DESIGN:
- The study will begin with belinostat 400 mg/m (2)/24h administered by continuous IV infusion on days 1 and 2, cisplatin at 80 mg/m (2) IV on day 2, and etoposide at 100 mg/m (2) IV daily times 3 on days 2 - 4. Dose escalation of belinostat will follow according to traditional 3 patient cohorts.
- Treatment schedule and dose escalation schemata.
Read the detailed description
BACKGROUND:
- The histone deacetylase (HDAC) inhibitors are a novel class of anticancer agent. These agents lead to the increased acetylation of both histone and non-histone proteins, which leads to rapid cell death in many tumor models. It is thought that the cell death observed with this class of agents may be mediated, in part, through the selective acetylation of histone proteins resulting in increased expression of specific genes.
- For solid tumors in general, cell death in preclinical models has not translated to activity in patients. For this reason, studies increasingly have combined chemotherapy with HDAC inhibitors to achieve additive and potentially synergistic effects on cancer cells.
- This protocol will study a continuous infusion of the HDAC inhibitor belinostat in combination with cisplatin and etoposide for patients with advanced cancer.
OBJECTIVES:
- To determine a safe and tolerable phase 2 dose for the combination of belinostat with cisplatin and etoposide.
- Evaluate molecular markers of HDAC inhibition.
- To explore the results of administering the dose of belinostat based on the patients' UGT1A1 *28 or *60 genotype, which is a characteristic that may be associated with toxicity.
ELIGIBILITY:
- The protocol will be open to all patients with recurrent or advanced cancer (small-cell lung cancer and other advanced cancers) for whom standard therapy offers no curative potential.
- Age greater than or equal to 18 years
- ECOG Performance Status 0-2
DESIGN:
- The study will begin with belinostat 400 mg/m (2)/24h administered by continuous IV infusion on days 1 and 2, cisplatin at 60 mg/m(2) IV on day 2, and etoposide at 80 mg/ (2) IV daily times 3 on days 2 - 4. Dose escalation of belinostat will follow according to traditional 3 patient cohorts.
- With Amendment M, dosing will be based on UGT1A1 status, at either 400 mg/m(2) or 600 mg/m(2)
- Keywords
- Solid Tumors, Histone deacetylase inhibitors, EP & Belinostat, Phase I, SCLC, Small Cell Lung Cancer
- Medical subject headings
- Carcinoma, Neuroendocrine, Small Cell Lung Carcinoma, Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BelinostatDrug
6 cycles of belinostat 400 mg/m2/24h X2 administered by CIV
CisplatinDrug
6 cycles at 60mg/m2 IV on day 2
EtoposideDrug
6 cycles 80 mg/m2 IV daily X3 beginning day 2.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Belinostat dose escalation Receives: Drug: Belinostat; Drug: Cisplatin; Drug: Etoposide |
| 2 | Experimental | Belinostat UGT1A1 wild type/*28 variant Receives: Drug: Belinostat; Drug: Cisplatin; Drug: Etoposide |
| 3 | Experimental | Belinostat UGT1A1*60 or 2/3/4 variant Receives: Drug: Belinostat; Drug: Cisplatin; Drug: Etoposide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability
Measured: Dose Limiiting Toxicity
Secondary outcomes (4)
Markers of HDAC
Measured: End of treatment
Tumor response
Measured: Disease Progression
miRNA and CGH
Measured: End of treatment
Increased acetylation in PBMCs
Measured: End of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jun 2009 (estimated)
- Study start1 Jul 2009
- Primary completion16 Jun 2017
- Study completion20 Apr 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Carcinoma NeuroendocrineStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Anish Thomas, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00926640
- Sponsor's protocol ID
- 090173
- Other IDs
- 09-C-0173
- Status last verified
- 20 Apr 2018
- First submitted
- 20 Jun 2009
- Last updated
- 19 Oct 2018
- Results posted
- No
Publications
Akerley W, McCoy J, Hesketh PJ, Goodwin JW, Bearden JD, Atkins JN, Chansky K, Crowley JJ, Gandara DR; SWOG. Gemcitabine and irinotecan for patients with untreated extensive stage small cell lung cancer: SWOG 0119. J Thorac Oncol. 2007 Jun;2(6):526-30. doi: 10.1097/JTO.0b013e318060d2dc.
PubMed 17545848Bevins RL, Zimmer SG. It's about time: scheduling alters effect of histone deacetylase inhibitors on camptothecin-treated cells. Cancer Res. 2005 Aug 1;65(15):6957-66. doi: 10.1158/0008-5472.CAN-05-0836.
PubMed 16061681Camphausen K, Scott T, Sproull M, Tofilon PJ. Enhancement of xenograft tumor radiosensitivity by the histone deacetylase inhibitor MS-275 and correlation with histone hyperacetylation. Clin Cancer Res. 2004 Sep 15;10(18 Pt 1):6066-71. doi: 10.1158/1078-0432.CCR-04-0537.
PubMed 15447991Peer CJ, Hall OM, Sissung TM, Piekarz R, Balasubramaniam S, Bates SE, Figg WD. A population pharmacokinetic/toxicity model for the reduction of platelets during a 48-h continuous intravenous infusion of the histone deacetylase inhibitor belinostat. Cancer Chemother Pharmacol. 2018 Sep;82(3):565-570. doi: 10.1007/s00280-018-3631-7. Epub 2018 Jun 27.
PubMed 29951694
Study at a glance
From the registry record, last updated by the sponsor on 19 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of Belinostat in Combination With Cisplatin and Etoposide in Adults With a Focus on Small Cell Lung Cancer and Other Cancers of Neuroendocrine Origin
- ClinicalTrials.gov ID
- NCT00926640
- Acronym / sponsor ID
- 090173
- Keywords
- Solid Tumors, Histone deacetylase inhibitors, EP & Belinostat, Phase I, SCLC, Small Cell Lung Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 1 Jul 2009
- Primary completion
- 16 Jun 2017 (actual)
- Study completion
- 20 Apr 2018 (actual)
- First posted
- 23 Jun 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.
BACKGROUND:
- The histone deacetylase (HDAC) inhibitors are a novel class of anticancer agent. These agents lead to the increased acetylation of both histone and non-histone proteins, which leads to rapid cell death in many tumor models. It is thought that the cell death observed with this class of agents may be mediated, in part, through the selective acetylation of histone proteins resulting in increased expression of specific genes.
- For solid tumors in general, cell death in preclinical models has not translated to activity in patients. For this reason, studies increasingly have combined chemotherapy with HDAC inhibitors to achieve additive and potentially synergistic effects on cancer cells.
- This protocol will study a continuous infusion of the HDAC inhibitor belinostat in combination with cisplatin and etoposide for patients with advanced cancer.
OBJECTIVES:
- To determine a safe and tolerable phase 2 dose for the combination of belinostat with cisplatin and etoposide.
- Evaluate molecular markers of HDAC inhibition.
ELIGIBILITY:
- The protocol will be open to all patients with recurrent or advanced cancer (small-cell lung cancer and other advanced cancers) for whom standard therapy offers no curative potential.
- Age greater than or equal to 18 years
- ECOG Performance Status 0-2
DESIGN:
- The study will begin with belinostat 400 mg/m (2)/24h administered by continuous IV infusion on days 1 and 2, cisplatin at 80 mg/m (2) IV on day 2, and etoposide at 100 mg/m (2) IV daily times 3 on days 2 - 4. Dose escalation of belinostat will follow according to traditional 3 patient cohorts.
- Treatment schedule and dose escalation schemata.
Detailed description
BACKGROUND:
- The histone deacetylase (HDAC) inhibitors are a novel class of anticancer agent. These agents lead to the increased acetylation of both histone and non-histone proteins, which leads to rapid cell death in many tumor models. It is thought that the cell death observed with this class of agents may be mediated, in part, through the selective acetylation of histone proteins resulting in increased expression of specific genes.
- For solid tumors in general, cell death in preclinical models has not translated to activity in patients. For this reason, studies increasingly have combined chemotherapy with HDAC inhibitors to achieve additive and potentially synergistic effects on cancer cells.
- This protocol will study a continuous infusion of the HDAC inhibitor belinostat in combination with cisplatin and etoposide for patients with advanced cancer.
OBJECTIVES:
- To determine a safe and tolerable phase 2 dose for the combination of belinostat with cisplatin and etoposide.
- Evaluate molecular markers of HDAC inhibition.
- To explore the results of administering the dose of belinostat based on the patients' UGT1A1 *28 or *60 genotype, which is a characteristic that may be associated with toxicity.
ELIGIBILITY:
- The protocol will be open to all patients with recurrent or advanced cancer (small-cell lung cancer and other advanced cancers) for whom standard therapy offers no curative potential.
- Age greater than or equal to 18 years
- ECOG Performance Status 0-2
DESIGN:
- The study will begin with belinostat 400 mg/m (2)/24h administered by continuous IV infusion on days 1 and 2, cisplatin at 60 mg/m(2) IV on day 2, and etoposide at 80 mg/ (2) IV daily times 3 on days 2 - 4. Dose escalation of belinostat will follow according to traditional 3 patient cohorts.
- With Amendment M, dosing will be based on UGT1A1 status, at either 400 mg/m(2) or 600 mg/m(2)
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: Belinostat, Drug: Cisplatin, Drug: EtoposideBelinostat dose escalation |
| 2 | Experimental | Drug: Belinostat, Drug: Cisplatin, Drug: EtoposideBelinostat UGT1A1 wild type/*28 variant |
| 3 | Experimental | Drug: Belinostat, Drug: Cisplatin, Drug: EtoposideBelinostat UGT1A1*60 or 2/3/4 variant |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (12 listed)
- Patients who have not recovered (CTCAE less than or equal to grade 1) from adverse events due to prior treatments, except for alopecia or base stable grade 2 tinnitus (not interfering with ADL s) or stable grade 2 sensory neuropathy without pain or motor component, and not interfering with ADL s.
- Patients may not have received more than 2 prior cytotoxic regimens.
- Patients may not be receiving any other investigational agent with therapeutic anticancer intent.
- Patients may not have taken another histone deacetylase inhibitor (i.e. valproic acid, vorinostat) for at least 2 weeks prior to enrollment.
- Patients with history of CNS metastasis may not be enrolled on the study, unless control has been achieved with either radiation or surgical resection at least 3 months prior to enrollment on study.
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 |
|---|---|---|
| Belinostat6 cycles of belinostat 400 mg/m2/24h X2 administered by CIV | Drug | 1, 2, 3 |
| Cisplatin6 cycles at 60mg/m2 IV on day 2 | Drug | 1, 2, 3 |
| Etoposide6 cycles 80 mg/m2 IV daily X3 beginning day 2. | Drug | 1, 2, 3 |
Primary outcome
Safety and tolerability
Time frame: Dose Limiiting Toxicity
4 secondary outcomes
Markers of HDAC
Time frame: End of treatment
Tumor response
Time frame: Disease Progression
miRNA and CGH
Time frame: End of treatment
Increased acetylation in PBMCs
Time frame: End of treatment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Oct 2018.
- Background: PubMed 17545848Akerley W, McCoy J, Hesketh PJ, Goodwin JW, Bearden JD, Atkins JN, Chansky K, Crowley JJ, Gandara DR; SWOG. Gemcitabine and irinotecan for patients with untreated extensive stage small cell lung cancer: SWOG 0119. J Thorac Oncol. 2007 Jun;2(6):526-30. doi: 10.1097/JTO.0b013e318060d2dc.
- Background: PubMed 16061681Bevins RL, Zimmer SG. It's about time: scheduling alters effect of histone deacetylase inhibitors on camptothecin-treated cells. Cancer Res. 2005 Aug 1;65(15):6957-66. doi: 10.1158/0008-5472.CAN-05-0836.
- Background: PubMed 15447991Camphausen K, Scott T, Sproull M, Tofilon PJ. Enhancement of xenograft tumor radiosensitivity by the histone deacetylase inhibitor MS-275 and correlation with histone hyperacetylation. Clin Cancer Res. 2004 Sep 15;10(18 Pt 1):6066-71. doi: 10.1158/1078-0432.CCR-04-0537.
- Derived from this study: PubMed 29951694Peer CJ, Hall OM, Sissung TM, Piekarz R, Balasubramaniam S, Bates SE, Figg WD. A population pharmacokinetic/toxicity model for the reduction of platelets during a 48-h continuous intravenous infusion of the histone deacetylase inhibitor belinostat. Cancer Chemother Pharmacol. 2018 Sep;82(3):565-570. doi: 10.1007/s00280-018-3631-7. Epub 2018 Jun 27.
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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.
Anish Thomas, M.D. principal investigator
National Cancer Institute (NCI)
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 Belinostat, Cisplatin and Etoposide in people with Carcinoma Neuroendocrine and Small Cell Lung Carcinoma, run by National Cancer Institute (NCI) 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 12 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 19 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 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Safety and tolerability (time frame: Dose Limiiting Toxicity). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00926640, which also lists 4 linked publications.
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 19 Oct 2018.