Carboplatin and Etoposide Plus LBH589 for Small Cell Lung Cancer

NCT00958022 | Terminated Phase 1 DMC

• 1 other identifier: 08-035
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Evaluation of Target Lesions

  18 weeks

Secondary Outcomes (1)

• Evaluation of Best Overall Response

  18 weeks

Study Arms (1)

LBH589 and carboplatin with etoposide

EXPERIMENTAL

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

Interventions

LBH589 and carboplatin with etoposide DRUG

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.

Also known as: Etoposide: VP-16, VePesid, VP-16-213, EPEG, epipodophyllotoxin, NSC #141540, Carboplatin: Paraplatin, CBDCA, Paraplatin NovaPlus

LBH589 and carboplatin with etoposide

Eligibility Criteria

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

You may qualify if:

• Patients with extensive stage SCLC who have not received prior chemotherapy
• For the phase I portion of the study only (and not for phase II), patients with progressive advanced or metastatic cancer (any histology) are allowed. These patients must have progressed on one or more standard therapies for the disease, or have disease which is known to be incurable and poorly responsive to available systemic therapies. Priority will be given in patients with neuroendocrine tumors, such as:
• Carcinoid
• Extrapulmonary small cell carcinoma
• Peripheral neuroepithelioma
• Merkel cell tumor
• Neuroblastoma
• Large cell neuroendocrine cancer
• Esthesioneuroblastoma and other neuroendocrine carcinomas of the head and neck 1.2 For the phase I portion of the study only (and not for phase II), patients are allowed to have prior chemotherapy except for Etoposide and LBH589.
• Measurable disease (RECIST) (for phase II part only)
• Patients may not have received prior HDACi therapy, including valproic acid, for the treatment of any medical condition.
• ECOG Performance Status of ≤ 2 (see Appendix 4)
• Aged ≥ 18 years old and ability to provide written informed consent obtained prior to participation in the study and any related procedures being performed
• Patients must meet the following laboratory criteria:
• Hematology:

You may not qualify if:

• Prior HDAC, DAC, HSP90 inhibitors or valproic acid for the treatment of cancer
• Patients who will need valproic acid for any medical condition during the study or within 5 days prior to first LBH589 treatment
• Impaired cardiac function including any one of the following:
• Screening ECG with a QTc \> 450 msec confirmed by treating physician investigator prior to enrollment to the study
• Patients with congenital long QT syndrome
• History of sustained ventricular tachycardia
• Any history of ventricular fibrillation or torsades de pointes
• Bradycardia defined as heart rate \< 50 beats per minute. Patients with a pacemaker and heart rate ≥ 50 beats per minute are eligible.
• Patients with a myocardial infarction or unstable angina within 6 months of study entry
• Congestive heart failure (NY Heart Association class III or IV)
• Right bundle branch block and left anterior hemiblock (bifascicular block)
• Uncontrolled hypertension. Patients with history of hypertension must be well-controlled (≤140/90) on a stable regimen of anti-hypertensive therapy.
• Concomitant use of drugs with a risk of causing torsades de pointes (See Appendix 1.-1)
• Concomitant use of CYP3A4 inhibitors (See Appendix 1.-2)
• Patients with unresolved diarrhea \> CTCAE grade 1

Sponsors & Collaborators

• Ahmad Tarhini: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (1)

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

MeSH Terms

Conditions

Small Cell Lung Carcinoma

Interventions

Panobinostat; Carboplatin; Etoposide; Podophyllotoxin

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Hydroxamic Acids; Hydroxylamines; Amines; Organic Chemicals; Hydroxy Acids; Carboxylic Acids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coordination Complexes; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Lignans; Benzyl Compounds; Benzene Derivatives

Study Officials

• Ahmad A Tarhini, MD

  UPMC/UPCI

  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 INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: August 10, 2009
• First Posted: August 13, 2009
• Study Start: September 1, 2009
• Primary Completion: June 1, 2011
• Study Completion: June 1, 2011
• Last Updated: June 22, 2017

Record last verified: 2017-06

Locations

US (1)