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A Clinical Phase I / II Trial of Belinostat in Combination With Erlotinib in Patients With Non-small Cell Lung Cancer

Phase 1/Phase 2
18 Years
Not Enrolling
Non Small Cell Lung Cancer

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Trial Information

A Clinical Phase I / II Trial of Belinostat in Combination With Erlotinib in Patients With Non-small Cell Lung Cancer

Belinostat, developed by CuraGen, belongs to a new class of hydroxymat-type histone
deacetylase (HDAC) inhibitors. HDAC inhibitors, including Belinostat, has shown marked in
vitro and in vivo activity against a number of solid tumors and hematological cancers.
Belinostat has proven to be effective as a single agent or in combination with other
anticancer agents such as doxorubcin, paclitaxel, carboplatin, fluorouracil, bortezumib, and
there has been observed synergy between Belinostat or other HDAC inhibitors and EGFR
inhibitors gefinitinib and erlonitib.

Furthermore, the antineoplastic activity of Belinostat seen in preclinical experiments have
resulted in only moderate toxicity.

In the two Phase I trials of Belinostat for solid tumors and hematological malignancies
Belinostat have been well tolerated at doses up to 2000 mg daily in more than 100 patients.

Fatigue, nausea and vomiting has been the main side effects and with none or very mild
hematologic toxicity. Approximately 25% of patients in the study of solid tumors achieved
stable disease.

Inclusion Criteria:

1. Signed consent of an approved informed consent form

2. A. For the dose escalation phase: Patients with histological or cytological confirmed
non-small cell lung cancer who are rated suitable for treatment with Erlotinib B. For
MTD expansion phase: Patients diagnosed with non- small cell lung cancer rated
suitable for treatment with Erlotinib and with measurable disease according to RECIST
version 1.1

3. Performance status (ECOG) ≤ 2

4. Life expectancy at least 3 months

5. Age ≥ 18 years

6. Acceptable liver, kidney and bone marrow function, defined as:

- Bilirubin ≤ 1.5 x upper limit of normal (ULN)

- ASAT, ALAT and alkaline phosphatase ≤ 3 x ULN (if liver metastases is ≤ 5 x ULN

- Serum creatinine ≤ 1.5 x upper limit of normal (ULN)

- WBC> 2.5 x 109 / l, neutrophils> 1.0 x 109 / l, platelets> 100 x 109 / l

- Hemoglobin> 9.0 g / dl or> 5.6 mmol / l

7. Acceptable coagulation: PT and APTT within ≤ 1.5 x ULN or in the therapeutic range if
given anticoagulant

8. A negative pregnancy test for women of childbearing age. In fertile men and women the
use of effective contraception methods are required during the trial

9. Serum potassium within normal range

Exclusion Criteria:

1. Treatment with experimental drugs within the last 4 weeks

2. Former anti-cancer therapy within the last 3 weeks before the start of experimental
treatment, including chemotherapy, radiotherapy, endocrine therapy or immunotherapy

3. Simultaneous presence of active infection or other concomitant present medical
condition likely to affect the experimental procedures, including significant
cardiovascular disease (New York Heart Association Class III or IV heart disease,
myocardial infarction within the past 6 months, unstable angina, congestive heart
failure requiring treatment, unstable arrhythmia or the need for antiarrhythmic drugs
or signs of ischemia on ECG, marked baseline prolongation of QT / QTc interval, for
example repeated demonstration of a QTc interval> 500 msec; long QT syndrome;
required the use of concurrent medication on dosage belinostat days, which may cause
torsades de pointes (see Appendix 1).

4. Altered mental status that prevents understanding of the informed consent process and
/ or execution of the necessary experiments

5. Secondary malignancy present (previous malignancy accepted if cured by treatment for
> 3 years ago)

6. Intestinal obstruction or threatening bowel obstruction

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:


Outcome Description:

The primary purpose of the phase I part of the trial is to establish the tolerance dose (maximum tolerated dose (MTD) and dose limiting toxicity (DLT).

Outcome Time Frame:

1 year

Safety Issue:


Principal Investigator

Jon L Andersen, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Dept of Oncology Copenhagen University Hospital Herlev


Denmark: Danish Medicines Agency

Study ID:




Start Date:

December 2010

Completion Date:

August 2012

Related Keywords:

  • Non Small Cell Lung Cancer
  • Non small cell lung cancer
  • Belinostat
  • Erlotinib
  • HDAC inhibitor
  • Phase I/II
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms