Carboplatin and Etoposide Plus LBH589 for Small Cell Lung Cancer
The subjects are being asked to take part in the Phase I or Phase II portion of a research study of a new investigational drug, LBH589, in combination with chemotherapeutic agents, carboplatin with etoposide. LBH589 (made by Novartis Pharmaceuticals Corp.) is considered "investigational" because it has not been approved for commercial use in the treatment of cancer by the U.S. Food and Drug Administration (FDA). Etoposide and carboplatin are chemotherapeutic agents approved by the FDA for the treatment of for small cell lung cancer.
LBH589 is a drug that may slow down the growth of cancer cells or kill cancer cells by blocking certain enzymes (proteins produced by cells). LBH589 has shown effects against cancer in laboratory studies and in studies using animals; however, it is not known if this medicine will show the same activity in humans. As of May 2006, approximately 100 patients have received treatment with either an intravenous or capsule form of LBH589. Only the capsule form of LBH589 will be used in this study.
The main goal during the Phase I portion of this research study is to find out the highest and safest dose of LBH589 that can be given in combination with carboplatin with etoposide in subjects with lung cancer without causing severe side effects. The main goal of the Phase II portion of this study is to find how the subject's lung cancer responds to the LBH589 in combination with carboplatin and etoposide at the highest and safest dose that was given in Phase I.
The subject may be enrolled in either Phase I or Phase II of the trial, depending on when they entered the study, but they will not be enrolled in both phases.
This study will also investigate how the subject's body processes the combination of LBH589 and carboplatin with etoposide. To determine this, the investigators will measure the amount of study drug in the subject's blood. This will be done with a series of blood tests, called pharmacokinetic (PK) tests. Pharmacokinetics is the study of how the study drug moves through the body. Other purposes of this study will be to sample the subject's genetic material (DNA/RNA) as well as to determine biomarkers in their blood. (For some cancers, biomarkers are a way to measure the extent of their disease or the effects of treatment.) These samples will also be stored for future studies.
Small Cell Lung Cancer
Drug: LBH589 and carboplatin with etoposide
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I/ II Trial of Carboplatin and Etoposide Plus LBH589 for Previously Untreated Extensive Stage Small Cell Lung Cancer|
- Evaluation of Target Lesions [ Time Frame: 18 weeks ] [ Designated as safety issue: No ]
- Evaluation of Best Overall Response [ Time Frame: 18 weeks ] [ Designated as safety issue: No ]
|Study Start Date:||September 2009|
|Study Completion Date:||June 2011|
|Primary Completion Date:||June 2011 (Final data collection date for primary outcome measure)|
Experimental: LBH589 and carboplatin with etoposide
The main goal during the Phase I portion of this research study is to find out the highest and safest dose of LBH589 that can be given in combination with carboplatin with etoposide in subjects with lung cancer without causing severe side effects. The main goal of the Phase II portion of this study is to find how lung cancer responds to the LBH589 in combination with carboplatin and etoposide.
This study will also investigate how the body processes the combination of LBH589 and carboplatin with etoposide.
Drug: LBH589 and carboplatin with etoposide
LBH589 will be given in oral formulation starting at a dose of 10 mg (Dose Level 1) 3x/week (2 days apart, e.g. Mon, Wed, Fri), during 2 weeks out of 3-weekly dosing schedule. After establishing the MTD at a 2 out 3 weeks dosing schedule, a 3 out of 3 weeks dosing schedule will be tested at that dose. This schedule will be adopted in the absence of limiting toxicities. Will be continued weekly after completion of 6 cycles of combo chemotherapy until progression or intolerable toxicities.
Etoposide: Cycles 1-6: 100 mg/m² IV over 60 mins, Days 1-3 every 21 days for 6 cycles Carboplatin: commercially available as a sterile lyophilized powder available in single dose vials containing 50mg, 150mg, or 450mg of carboplatin. Each vial contains equal parts by weight of carboplatin & mannitol. Commercial supplies will be used for this study. It will be administered as an i.v. infusion over 30 minutes. The dose will be calculated based on patient's body weight at each treatment visit.
- LBH589 will be given in oral formulation starting at a dose of 10 mg (Dose Level 1) three times per week (doses will be given at least 2 days apart, e.g. Monday, Wednesday, Friday), 2 out of 3 weeks dosing schedule.
- After establishing the MTD of LBH589 at a 2 out 3 weeks dosing schedule, a 3 out of 3 weeks dosing schedule will be tested at that dose, and this schedule will be adopted in the absence of limiting toxicities.
- Carboplatin will be given on day 1, every 21 days, and etoposide on days 1,2,3 every 21 days for up to 6 cycles. LBH589 will be continued weekly, three times-a-week, without interruption after completion of 6 cycles of combination chemotherapy until progression, or intolerable toxicities.
In the phase I part and for cycle 1 only, for the purpose of the PK studies LBH589 will start the week prior to the first carboplatin/etoposide cycle and PD studies will be performed (week -1).
Study design and sample size:
This is a phase I/II study. Phase I: 15-24 patients (estimated; Three to six patients will be enrolled at each dose level); Phase II: 39 patients.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00958022
|United States, Pennsylvania|
|University of Pittsburgh|
|Pittsburgh, Pennsylvania, United States, 15213|
|Principal Investigator:||Ahmad A Tarhini, MD||UPMC/UPCI|