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

Plain-language summary

This study evaluates the drug Belinostat in combination with Cisplatin and Etoposide in adults with small cell lung cancer and other advanced cancers for which no standard therapy exists. It included patients with confirmed cancer. It was a Phase 1 study and has been completed.

The summary above is a plain-language rendering of the official record. The original English title is shown for reference.

Trial details

Phase

Phase 1

Status

Completed

Sponsor

National Cancer Institute (NCI)

Intervention

Belinostat, Cisplatin, Etoposide

Start date

7/1/2009

Estimated completion

4/20/2018

Countries

United States

Related genes

Locations

• Bethesda, United States

Eligibility criteria

Criteria are reproduced from the ClinicalTrials.gov record in the original English. Only the trial team can determine eligibility.

-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.