Non Small Cell Lung Cancer
Conditions
Keywords
Non small cell lung cancer, Belinostat, Erlotinib, HDAC inhibitor, Phase I/II
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.
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.
Interventions
DRUGBelinostat 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.
Sponsors
Copenhagen University Hospital at Herlev
Bispebjerg Hospital
Valerio Therapeutics
Roche Pharma AG
Herlev Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety | 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
| Measure | Time frame | Description |
|---|---|---|
| Efficacy | 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 |
Countries
Denmark
Outcome results
None listed