Combination of the Hedgehog Inhibitor, LDE225, With Etoposide and Cisplatin in the First-Line Treatment of Patients With Extensive Stage Small Cell Lung Cancer (ES-SCLC)
The purpose of this study is to test the safety of study drug LDE225 at different dose levels. The investigators will be testing three different dose levels and the dose will depend on when the patients enters the study and which dose is being tested at that time. At the same time, the investigators will also be testing the safety of LDE225 in combination with etoposide and cisplatin.
The investigators also want to learn more about how to manage side effects the patient may develop during chemotherapy. Cancer patients may develop side effects during treatment, such as nausea, pain, fatigue, diarrhea, constipation, or shortness of breath. These symptoms may be due to the cancer itself, or due to treatments. Doctors and nurses often ask patients about their symptoms, because an important part of cancer treatment is to make patients feel as well as possible. If patients do not feel well, the investigators may need to change the way they are treating the patients or prescribe therapies that will decrease their symptoms.
The best way to find out how the patient is feeling is to ask them directly. The investigators are interested in developing new ways to ask patients about how they are feeling, using the Internet. A special new website called STAR ("Symptom Tracking and Reporting for Patients") has been developed to help patients record this information, so that their doctors and nurses can review it during clinic appointments. This study is designed to help us see if STAR is a helpful way for us to keep track of information about patients' symptoms and quality of life. The information from STAR is going to be placed on a very secure Internet site. This will provide your doctor with all of the information needed to determine if this drug combination is safe enough for you and whether to continue it.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Trial of the Combination of the Hedgehog Inhibitor, LDE225, With Etoposide and Cisplatin in the First-Line Treatment of Patients With Extensive Stage Small Cell Lung Cancer (ES-SCLC)|
- MTD [ Time Frame: 1 year ] [ Designated as safety issue: No ]A standard 3 + 3 dose escalation design will be used in order to determine MTD. Two proposed dose levels of LDE225 will be tested with etoposide and cisplatin (400 mg and 800 mg; one additional dose (200 mg) is reserved for de-escalation. Patients will be evaluated for DLT after 2 cycles on therapy.
- safety, tolerability [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]All patients who receive at least one dose of LDE225 with etoposide and cisplatin will be included in the descriptive analysis of safety and toxicity. Adverse events will be graded according to CTCAE version 4.0 and tabulated individually.
- pharmacokinetic profile [ Time Frame: 1 year ] [ Designated as safety issue: No ]Blood samples for the determination of LDE225 pharmacokinetics (PK) and its active metabolite(s) will be collected from all patients during the study. Blood samples will be collected prior to the administration of LDE225 on day 1 of cycles 1 through 9.
- efficacy [ Time Frame: 1 year ] [ Designated as safety issue: No ]Patients on study will be followed and assessed for response as per RECIST 1.1. Complete and partial response must be confirmed by a subsequent tumor assessment. Unconfirmed partial response will be classified as stable disease.
- patient-reported outcomes (toxicity-related symptoms) [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]According to CTCAE version 4.0 using wireless touchscreen laptop computers in the outpatient clinics via the MSKCC STAR system and evaluate the extent to which clinicians will concur with these and how clinicians will use this information for dose-finding in a phase I clinical trial.
|Study Start Date:||April 2012|
|Estimated Study Completion Date:||April 2017|
|Estimated Primary Completion Date:||April 2017 (Final data collection date for primary outcome measure)|
Experimental: LDE225, Etoposide and Cisplatin
This is a single institution phase I trial of LDE225 combined with etoposide and cisplatin in patients with untreated, newly diagnosed extensive stage small cell lung cancer (ES-SCLC). LDE225 is an oral drug, which will be taken daily by patients. Patient self-reporting via STAR will be used in an evaluation of the extent to which patient-reported toxicity influences dose finding in phase I clinical trials. Specifically, STAR reports will be presented to clinicians in real-time at clinic visits, & clinicians will have an opportunity to either agree or modify the patient self-assessments & use this information in their grading & attribution of toxicities.
Drug: LDE225, Etoposide and Cisplatin
In a standard, 3 + 3 dose escalation phase, two successive cohorts of ES-SCLC patients will receive LDE225 with etoposide and cisplatin with a dose of 200 mg to be reserved for de-escalation until the MTD is determined. Cohorts of at least 3 evaluable patients will be treated at each dose level of LDE225 (400 mg daily and 800 mg daily). One additional dose (200 mg daily) will be reserved for de-escalation. A minimum of 6 evaluable patients must be treated at the dose declared to be the MTD. Each cohort will consist of newly enrolled patients. An estimated total of 6 to 12 patients may be necessary to establish the MTD. Actual accrual will depend on the dose levels tested and the DLT observed. Upon completion of a minimum of four and a maximum of six cycles of LDE225 with etoposide and cisplatin, patients in each cohort with at least stable disease will receive maintenance LDE225 until disease progression or unacceptable toxicity.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01579929
|United States, New Jersey|
|Memoral Sloan Kettering Cancer Center|
|Basking Ridge, New Jersey, United States|
|United States, New York|
|Memorial Sloan Kettering Cancer Center at Commack|
|Commack, New York, United States, 11725|
|Memorial Sloan Kettering Cancer Center|
|New York, New York, United States, 10065|
|Memorial Sloan Kettering Cancer Center at Mercy Medical Center|
|Rockville Centre, New York, United States, 11570|
|Memoral Sloan Kettering Cancer Center@Phelps Memorial Hospital|
|Sleepy Hollow, New York, United States|
|Principal Investigator:||Charles Rudin, MD||Memorial Sloan Kettering Cancer Center|