A Phase I Study of Belinostat in Combination With Cisplatin and Etoposide in Adults With Small Cell Lung Carcinoma and Other Advanced Cancers

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

28 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-07-01

Study Completion Date

2018-04-20

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

Cisplatin, Etoposide, and Bevacizumab in Treating Patients With Previously Untreated Extensive Stage Small Cell Lung Cancer

NCT00079040

Extensive Stage Small Cell Lung Cancer

COMPLETED PHASE2

Trial of Belotecan/Cisplatin in Chemotherapy Naive Small Cell Lung Cancer Patient

NCT00826644

Carcinoma, Small Cell

COMPLETED PHASE3

Safety and Efficacy of Belinostat When Used With Standard of Care Chemotherapy for Untreated Non-small Cell Lung Cancer

NCT01090830

Non-Small-Cell Lung Carcinoma

TERMINATED PHASE1/PHASE2

Cisplatin Plus Etoposide With or Without Paclitaxel in Treating Patients With Extensive-Stage Small Cell Lung Cancer

NCT00003299

Lung Cancer

COMPLETED PHASE3

S0124: Cisplatin Combined With Irinotecan or Etoposide For Extensive-Stage Small Cell Lung Cancer

NCT00045162

Lung Cancer

COMPLETED PHASE3

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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)

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Carcinoma Neuroendocrine Small Cell Lung Carcinoma Malignant Epithelial Neoplasms

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

1

Belinostat dose escalation

Group Type EXPERIMENTAL

Belinostat

Intervention Type DRUG

6 cycles of belinostat 400 mg/m2/24h X2 administered by CIV

Cisplatin

Intervention Type DRUG

6 cycles at 60mg/m2 IV on day 2

Etoposide

Intervention Type DRUG

6 cycles 80 mg/m2 IV daily X3 beginning day 2.

2

Belinostat UGT1A1 wild type/\*28 variant

Group Type EXPERIMENTAL

Belinostat

Intervention Type DRUG

6 cycles of belinostat 400 mg/m2/24h X2 administered by CIV

Cisplatin

Intervention Type DRUG

6 cycles at 60mg/m2 IV on day 2

Etoposide

Intervention Type DRUG

6 cycles 80 mg/m2 IV daily X3 beginning day 2.

3

Belinostat UGT1A1\*60 or 2/3/4 variant

Group Type EXPERIMENTAL

Belinostat

Intervention Type DRUG

6 cycles of belinostat 400 mg/m2/24h X2 administered by CIV

Cisplatin

Intervention Type DRUG

6 cycles at 60mg/m2 IV on day 2

Etoposide

Intervention Type DRUG

6 cycles 80 mg/m2 IV daily X3 beginning day 2.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Belinostat

6 cycles of belinostat 400 mg/m2/24h X2 administered by CIV

Intervention Type DRUG

Cisplatin

6 cycles at 60mg/m2 IV on day 2

Intervention Type DRUG

Etoposide

6 cycles 80 mg/m2 IV daily X3 beginning day 2.

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

1. Patients must have histologic or cytologic confirmation of cancer for which there is no known standard therapy capable of extending life expectancy.
2. Patients must be greater than or equal to 4 weeks from cytotoxic chemotherapy, except greater than or equal to 6 weeks for mitomycin C or nitrosoureas, and greater than or equal to 8 weeks from prior UCN01; greater than or equal to 4 weeks from monoclonal antibody therapy (cetuximab, bevacizumab); greater than or equal to 4 weeks from prior experimental therapy; greater than or equal 2 weeks from radiation or hormonal therapy; greater than or equal to 2 weeks from sorafenib, sunitinib or temsirolimus treatment. Patients with prostate cancer may continue ongoing LhRH agonist therapy. Patients with bone metastases or hypercalcemia who began intravenous bisphosphonate treatment prior to study entry may continue this treatment while on study.
3. ECOG performance status 0-2.
4. Life expectancy of 3 months or greater.
5. Patients must have acceptable organ and marrow function as defined below:

* absolute neutrophil count greater than or equal to 1,500/ mm(3)
* platelets greater than or equal to 100,000/ mm(3)
* total bilirubin less than or equal to 1.2 mg/dL (except patients with Gilbert's Syndrome)
* AST (SGOT) and ALT(SGPT) less than or equal to 2.5 times institutional upper limit of normal
* creatinine less than or equal to 1.5 times institutional upper limit of normal

OR

\- creatinine clearance \>50 mL/min/1.73 m(2) for patients with creatinine levels above institutional normal.
6. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, during the study, and for 3 months after study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
7. Age greater than or equal to 18 years.
8. Ability to understand and the willingness to sign a written informed consent document.
9. Willing to comply with study procedures and follow-up.

Exclusion Criteria

1. 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.
2. Patients may not have received more than 2 prior cytotoxic regimens.
3. Patients may not be receiving any other investigational agent with therapeutic anticancer intent.
4. Patients may not have taken another histone deacetylase inhibitor (i.e. valproic acid, vorinostat) for at least 2 weeks prior to enrollment.
5. 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.
6. 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).
7. 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.
8. HIV-positive patients.
9. Patients with acute or chronic hepatitis.
10. Pregnant patients may not receive this experimental therapy.
11. 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.
12. 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.

Minimum Eligible Age

18 Years

Maximum Eligible Age

99 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No