Phase 1b/2 Study of Carfilzomib, Carboplatin, and Etoposide in Subjects With Previously Untreated Extensive Stage Small-cell Lung Cancer

Extensive-Stage Small-Cell Lung Cancer Clinical Trial

Official title:

Phase 1b/2, Multicenter, Open-label Study of Carfilzomib, Carboplatin, and Etoposide in Subjects With Previously Untreated Extensive-stage Small-cell Lung Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01987232
• Other study ID #: CFZ004
• Secondary ID: 2013-002597-44
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: November 6, 2013
• Last updated: May 31, 2017
• Start date: September 2013
• Est. completion date: May 4, 2017

Study information

• Verified date: May 2017
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine the maximum tolerated dose and assess the safety, tolerability and activity of carfilzomib given in combination with carboplatin and etoposide as initial therapy for subjects with Extensive-Stage Small-Cell Lung Cancer (ES SCLC).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: May 4, 2017
• Est. primary completion date: August 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

1. Histologically or cytologically confirmed diagnosis of extensive-stage small-cell lung cancer (ES-SCLC) with measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1; ES-SCLC is defined as: small-cell lung cancer (SCLC) that has spread beyond one hemithorax and regional lymph nodes on the same side (e.g., supraclavicular) to the contralateral hemithorax, lymph nodes, or more distant locations in the body

2. Subjects with asymptomatic brain metastases or other central nervous system (CNS) disease at screening/diagnosis are eligible

3. Males and females = 18 years of age

4. Eastern Cooperative Oncology Group (ECOG) performance status 0-1

Key Exclusion Criteria:

1. Previous systemic therapy to treat small-cell lung cancer (SCLC). Subjects with recurrent or progressive limited-stage SCLC after previous systemic treatment are not eligible for study participation.

2. Whole brain or focal radiation therapy within 14 days prior to Cycle 1 Day 1 (C1D1) for Phase 1b or prior to randomization for Phase 2

3. Congestive heart failure (New York Heart Association [NYHA] class III to IV), symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention, or myocardial infarction within 6 months prior to prior to C1D1 for Phase 1b or prior to randomization for Phase 2

Related Conditions & MeSH terms

• Extensive-Stage Small-Cell Lung Cancer
• Lung Neoplasms
• Small Cell Lung Carcinoma

Intervention

Drug:
• Carfilzomib

• Carboplatin

• Etoposide

Locations

Country	Name	City	State
Canada	Juravinski Cancer Centre	Hamilton	Ontario
Russian Federation	State budgetary healthcare institution of Arkhangelsk Region "Arkhangelsk Clinical Oncological Dispensary"	Arkhangelsk
Russian Federation	Regional Budgetary Healthcare Institution "Kursk Regional Clinical Oncology Dispensary"	Kislino	Kursk
Russian Federation	Federal State Budgetary Scientific Institution "N.N. Blokhin Russian Cancer Research Center"	Moscow
Russian Federation	State Budgetary Educational Inslitution of Higher Professional Education "First St. Petersburg I.P.Pavlov State Medical University"	St. Petersburg
Russian Federation	State Budgetary Healthcare Institution of Yaroslavl Region "Regional Clinical Oncological Hospital"	Yaroslavl
United States	Levine Cancer Institute	Charlotte	North Carolina
United States	Frederick Memorial Hospital	Frederick	Maryland
United States	UF Health Davis Cancer Pavilion and Shands Med Plaza	Gainesville	Florida
United States	Goshen Center for Cancer Care	Goshen	Indiana
United States	John Theurer Cancer Center at Hackensack UMC	Hackensack	New Jersey
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Horizon Oncology Research, Inc.	Lafayette	Indiana
United States	Baptist Health Lexington Clinical Research Center	Lexington	Kentucky
United States	Indiana University Health Ball Memorial Hospital	Muncie	Indiana
United States	Yale University, Yale Cancer Center	New Haven	Connecticut
United States	Wake Forest Baptist Health	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Countries where clinical trial is conducted

United States,  Canada,  Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Tolerated Dose (MTD) - Phase 1b	To determine the MTD of carfilzomib given in combination with standard dose carboplatin (target AUC = 5; IV) on Day 1 and etoposide (100 mg/m2; IV) on Days 1, 2, and 3 every 3 weeks as treatment for previously untreated Extensive-stage Small-cell Lung Cancer (ES-SCLC). The MTD is defined as the highest dose level at which < 33% of subjects experience a dose-limiting toxicity (DLT) during the first 21-day cycle.	First 21-day Cycle
Primary	Progression-free Survival (PFS) - Phase 2	To evaluate the efficacy of carfilzomib with carboplatin and etoposide (carfilzomib combination arm) versus carboplatin and etoposide alone (control arm) in subjects with treatment-naïve ES-SCLC, as measured by progression-free survival (PFS).	24 months after the first subject is randomized
Secondary	Best Overall Response (BOR) - Phase 1b & Phase 2	Best Overall Response (BOR) is defined as either confirmed complete response (CR) or partial response (PR) per RECIST Version 1.1.	24 months after the first subject is randomized
Secondary	Duration of Response (DOR) - Phase 1b & Phase 2	Duration of Response (DOR) is defined as the time from first evidence of partial response (PR) or better to documented progressive disease (PD) or death due to any cause.	24 months after the first subject is randomized
Secondary	Overall Survival (OS) - Phase 2	Overall Survival (OS) is defined as the time from randomization to the date of death.	30 months after the first subject is randomized
Secondary	Adverse Events - Phase 1b & Phase 2	Number of patients that experience Adverse Events (AEs)	24 months after the first subject is randomized
Secondary	Maximum Plasma Concentration - Phase 2	Maximum plasma concentration (Cmax, observed)	Cycle 1 Day 2
Secondary	Time of Maximum Plasma Concentration - Phase 2	Time of maximum plasma concentration (Tmax, observed)	Cycle 1 Day 2
Secondary	Area Under Plasma Concentration-Time Curve - Phase 2	Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration and to infinity (AUC0-last and AUC0-8)	Cycle 1 Day 2