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A Trial of Belinostat in Combination With Erlotinib in Patients With Non-small Cell Lung Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01188707
Recruitment Status : Terminated (Dose over MTD reached)
First Posted : August 25, 2010
Last Update Posted : August 4, 2011
Copenhagen University Hospital at Herlev
Bispebjerg Hospital
Roche Pharma AG
Information provided by:
Herlev Hospital

Brief Summary:
The Belinostat-Erlotinib trial is designed as an open, non randomized phase I / II trial to assess the efficacy and safety of Belinostat in combination with Erlotinib in patients with non-small cell lung cancer who are eligible for treatment with erlotinib.

Condition or disease Intervention/treatment Phase
Non Small Cell Lung Cancer Drug: Belinostat and Erlotinib Phase 1 Phase 2

Detailed Description:

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 5 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Clinical Phase I / II Trial of Belinostat in Combination With Erlotinib in Patients With Non-small Cell Lung Cancer
Study Start Date : December 2010
Estimated Primary Completion Date : March 2012
Estimated Study Completion Date : August 2012

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Belinostat, Erlotinib, NSCLC Drug: Belinostat and Erlotinib

The design of the first phase is a 3 +3 phase I trial. The Belinostat dose will start at 500 mg and will be increased with 250 mg until a maximum dose of 1500 mg, administered daily in 2/3 weeks. Each patient will at the same time receive 150 mg of Erlotinib daily continously.

When the patient is enrolled at one dose level, there will be no further dose escalation for that individual patient.

3 patients will be treated at each dose level.

Other Name: Tarceva

Primary Outcome Measures :
  1. Safety [ Time Frame: 1 year ]
    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).

Secondary Outcome Measures :
  1. Efficacy [ Time Frame: 1 year ]
    The phase II part of the study is to assess the efficacy of Belinostat and Erlotinib in combination assessed by disease control rate, defined as non - progression at 3 months / Stable disease or better) using RECIST response criteria version 1.1

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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 allowed)
    • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01188707

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Dept of Oncology Copenhagen University Hospital Herlev
Herlev, Copenhagen, Denmark, 2730
Sponsors and Collaborators
Herlev Hospital
Copenhagen University Hospital at Herlev
Bispebjerg Hospital
Roche Pharma AG
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Principal Investigator: Jon L Andersen, MD Dept of Oncology Copenhagen University Hospital Herlev
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Responsible Party: MD Jon Lykkegaard Andersen, Dept. of Oncology Copenhagen University Hospital Herlev Identifier: NCT01188707    
Other Study ID Numbers: LU0928
First Posted: August 25, 2010    Key Record Dates
Last Update Posted: August 4, 2011
Last Verified: August 2011
Keywords provided by Herlev Hospital:
Non small cell lung cancer
HDAC inhibitor
Phase I/II
Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Erlotinib Hydrochloride
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Histone Deacetylase Inhibitors