A Trial of Belinostat in Combination With Erlotinib in Patients With Non-small Cell Lung Cancer
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.
Non Small Cell Lung Cancer
Drug: Belinostat and Erlotinib
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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|
- Safety [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]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).
- Efficacy [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]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
|Study Start Date:||December 2010|
|Estimated Study Completion Date:||August 2012|
|Estimated Primary Completion Date:||March 2012 (Final data collection date for primary outcome measure)|
|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
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.
|Dept of Oncology Copenhagen University Hospital Herlev|
|Herlev, Copenhagen, Denmark, 2730|
|Principal Investigator:||Jon L Andersen, MD||Dept of Oncology Copenhagen University Hospital Herlev|