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)

NCT01579929 | Completed Phase 1

• 1 other identifier: 11-206
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 5

Brief Summary

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.

Conditions

Lung Cancer

Keywords

Extensive Stage Small Cell Lung Cancer (ES-SCLC); CISPLATIN; ETOPOSIDE (VP-16); LDE-225; STAR; Symptom Tracking and Reporting for Patients; 11-206

Outcome Measures

Primary Outcomes (1)

• MTD

  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.

  1 year

Secondary Outcomes (4)

• safety, tolerability

  1 year

• pharmacokinetic profile

  1 year

• efficacy

  1 year

• patient-reported outcomes (toxicity-related symptoms)

  2 years

Study Arms (1)

LDE225, Etoposide and Cisplatin

EXPERIMENTAL

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

Interventions

LDE225, Etoposide and Cisplatin DRUG

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.

LDE225, Etoposide and Cisplatin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• SCLC pathologically confirmed at MSKCC.
• Untreated ES- SCLC, defined as those patients with extrathoracic metastatic disease, malignant pleural effusion, bilateral or contralateral supraclavicular lymphadenopathy, or contralateral hilar adenopathy.
• Age 18 years or older.
• Karnofsky Performance Status ≥ 70.
• Presence of at least one measurable site of disease as defined by Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1).
• Adequate bone marrow, liver and renal function, as specified below:
• Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L
• Hemoglobin (Hgb) ≥ 9 g/dL
• Platelets ≥ 100 x 109/L
• Serum total bilirubin ≤ 1.5 x upper limit of normal (ULN )
• AST and ALT ≤ 2.5 x ULN or ≤ 5 x ULN if liver metastases are present
• Plasma creatine phosphokinase (CK) \< 1.5 x ULN
• Serum creatinine ≤ 1.5 x ULN OR creatinine clearance ≥ 60ml/min for patients with creatinine levels above institutional normal.
• Patients with asymptomatic CNS metastases will be eligible. For patients that have undergone radiation therapy for their CNS metastases, a minimum of 14 days must elapse prior to study registration, and patients must have recovered from any adverse events related to radiotherapy with the exception of alopecia and grade 1 neuropathy.

You may not qualify if:

• Patients eligible for this study must not meet any of the following criteria:
• Patients who have had major surgery within 4 weeks of initiation of study medication.
• Patients who are unable to take oral drugs.
• Patients who have previously been treated with systemic LDE225 or with other Hh pathway inhibitors.
• Patients who have taken part in an experimental drug study within 4 weeks of initiating treatment with LDE225.
• Patients who are receiving other anti-neoplastic therapy (e.g. chemotherapy, targeted therapy, or radiotherapy) concurrently or within 2 weeks of starting treatment.
• Patients who have neuromuscular disorders (e.g. inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis and spinal muscular atrophy).
• Patients who are on concomitant treatment with drugs that are contraindicated in this study and that cannot be discontinued within the time frames as listed.
• Patients who are planning on embarking on a new strenuous exercise regimen that can result in significant increases in plasma CK levels.
• Patients who are receiving treatment with medications known to be moderate and strong inhibitors or inducers of CYP3A4/5 or with drugs metabolized by CYP2B6 or CYP2C9 that have narrow therapeutic index that cannot be discontinued before starting treatment with LDE225. Medications that are strong CYP3A4/5 inhibitors should be discontinued at least 7 days and strong CYP3A/5 inducers should be discontinued for at least 14 days prior to starting treatment with LDE225 Some of these medications are recognized to cause rhabdomyolysis.)
• Patients who are receiving treatment with statins that are known to cause rhabdomyolysis and that cannot be discontinued at least 2 days prior to starting LDE225 treatment.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements.
• Impaired cardiac function or clinically significant heart disease, including any one of the following: congestive heart failure, angina pectoris within 3 months, acute myocardial infarction within 3 months, QTcF \> 450 msec for males and \> 470 msec for females on the screening ECG, history of clinically significant ECG abnormalities, family history of prolonged QT-interval syndrome, or other clinically significant heart disease (e.g. congestive heart failure, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen).
• Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (\> 5 mIU/mL).
• Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and 4 months after the last study treatment. Highly effective contraception methods include the following:

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (5)

Memoral Sloan Kettering Cancer Center

Basking Ridge, New Jersey, United States

Location

Memorial Sloan Kettering Cancer Center at Commack

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Cancer Center at Mercy Medical Center

Rockville Centre, New York, 11570, United States

Location

Memoral Sloan Kettering Cancer Center@Phelps Memorial Hospital

Sleepy Hollow, New York, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Lung Neoplasms

Interventions

sonidegib; Etoposide; Cisplatin

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Charles Rudin, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 16, 2012
• First Posted: April 18, 2012
• Study Start: April 1, 2012
• Primary Completion: August 11, 2017
• Study Completion: August 11, 2017
• Last Updated: August 17, 2017

Record last verified: 2017-08

Locations

US (5)