A Study of BMS-833923 With Carboplatin and Etoposide Followed by BMS-833923 Alone in Subjects With Extensive-Stage Small Cell Lung Cancer

A Phase 1b Multiple Ascending Dose Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of BMS-833923 (XL139) in Combination With Carboplatin and Etoposide Followed by BMS-833923 Alone in Subjects With Extensive-Stage Small Cell Lung Cancer

The purpose of this study is to determine the maximum tolerated dose (MTD) of BMS-833923 administered in combination with carboplatin and etoposide followed by BMS-833923 alone in subjects with extensive-stage Small Cell Lung Cancer (SCLC).

Study Overview

• Status: Completed
• Conditions: Small Cell Lung Carcinoma
• Intervention / Treatment: Drug: BMS-833923; Drug: Carboplatin; Drug: Etoposide

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • East Bentleigh, Victoria, Australia, 3165
      • Local Institution
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Local Institution
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • Local Institution
• France
  • Villejuif Cedex, France, 94800
    • Local Institution
• Ireland
  • Dublin, Ireland
    • Local Institution
• United States
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologically or cytologically confirmed small cell lung cancer, without prior chemotherapy treatment
• Men and Women at least 18 years old
• Eastern Cooperative Oncology Group (ECOG) status 0-2

Exclusion Criteria:

• Significant cardiovascular disease
• Prior treatment of small cell lung cancer is not permitted, except for palliative radiation to a limited field excluding the chest (e.g. for painful metastasis).
• Symptomatic brain metastases
• Women pregnant or breastfeeding
• Women of childbearing potential (WOCBP) unwilling/unable to use acceptable method to avoid pregnancy
• Uncontrolled medical disorder or active infection
• Concurrent therapy with any other investigational product

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: All Subjects

Drug: BMS-833923; Capsule, Oral, starting dose 30 mg, once daily, continuous; Drug: Carboplatin; Vial, Intravenous (IV), dose to yield 5 mg/mL - min, once every 21 days, 1 day per cycle up to 4 cycles; Other Names: Paraplatin®; Drug: Etoposide; Vial, Intravenous (IV), 100 mg/m²/dose, days 1, 2, & 3 of each 21 day cycle, 3 days per cycle for up to 4 cycles; Other Names: VePesid®; Etopophos®; Toposar®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Use NCI CTCAE to establish the MTD, DLT(s) and safety profile of BMS-833923 administered alone and in combination with carboplatin and etoposide	NCI - National Cancer Institute; CTCAE - Common Terminology Criteria for Adverse Events; MTD - Maximum tolerated dose; DLT - Dose limiting toxicity	28 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetic parameters of BMS-833923 alone and in combination with carboplatin and etoposide: Maximum observed plasma concentration (Cmax)	Day 1 and 15 of first three 21-day cycles
Pharmacokinetic parameters of BMS-833923 alone and in combination with carboplatin and etoposide: Time of maximum observed plasma concentration (Tmax)	Day 1 and 15 of first three 21-day cycles
Pharmacokinetic parameters of BMS-833923 alone and in combination with carboplatin and etoposide: Area under the concentration-time curve in one dosing interval AUC(TAU)	Day 1 and 15 of first three 21-day cycles
Tumor assessments by computed tomography (CT) [as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1]	Every 6 weeks until disease progression
Pharmacodynamic effect (change from baseline) of BMS-833923 on Hedgehog pathway activation as measured by Glioma-associated oncogene -1 (GLI-1) expression	At baseline and after 1 week

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb
• Collaborators: Exelixis

Study record dates

Study Major Dates

• Study Start: February 1, 2010
• Primary Completion (Actual): September 1, 2012
• Study Completion (Actual): September 1, 2012

Study Registration Dates

• First Submitted: June 9, 2009
• First Submitted That Met QC Criteria: June 24, 2009
• First Posted (Estimate): June 25, 2009

Study Record Updates

• Last Update Posted (Estimate): June 3, 2013
• Last Update Submitted That Met QC Criteria: May 31, 2013
• Last Verified: May 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Small Cell Lung Carcinoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Carboplatin; Etoposide
• Other Study ID Numbers: CA194-005; 2010-018745-56 (EudraCT Number)