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

NCT01987232 | Completed Phase 1 Results

• 3 other identifiers: CFZ0042013-002597-4420130399
• Study Type: interventional
• Target: 32
• Locations: 3 countries
• Sites: 17

Brief 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 patients with extensive-stage small-cell lung cancer (ES SCLC).

Conditions

Extensive-Stage Small-Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Dose-limiting Toxicities

  The maximum tolerated dose (MTD) was defined as the highest dose level at which \< 33% of participants experienced a dose-limiting toxicity (DLT) during the first 21-day cycle. Dose-limiting toxicities were evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03. A DLT was defined as: * A grade 3 or greater non-hematologic toxicity that was assessed as related to carfilzomib by the investigator except in the case of neuropathy. A grade 2 or higher neuropathy with pain was considered a DLT. * Grade 4 neutropenia: absolute neutrophil count (ANC) \< 500 mm³, lasting ≥ 7 days despite granulocyte colony stimulating factor support, or any febrile (temperature \> 38.3°C) neutropenia (ANC \< 1000 mm³). * Thrombocytopenia of any grade associated with clinically significant bleeding or platelet/blood transfusion * Grade 4 fatigue lasting ≥ 7 days * Grade 3 nausea, vomiting or diarrhea lasting ≥ 7 days.

  First 21-day Cycle

Secondary Outcomes (5)

• Number of Participants With Adverse Events (AEs)

  From first day of any study treatment (i.e., carfilzomib, carboplatin, or etoposide) up to 30 days after the last day of study treatment. The median overall duration of treatment was 16 weeks.

• Overall Survival (OS) - Phase 2

  30 months

• Maximum Plasma Concentration - Phase 2

  Cycle 1 Day 2

• Time of Maximum Plasma Concentration - Phase 2

  Cycle 1 Day 2

• Area Under Plasma Concentration-Time Curve - Phase 2

  Cycle 1 Day 2

Other Outcomes (3)

• Progression-free Survival

  From first dose of study drug until the end of treatment; median duration of treatment was 16 weeks.

• Overall Response Rate

  From first dose of study drug until the end of treatment; median duration of treatment was 16 weeks.

• Duration of Response

  From first dose of study drug until the end of treatment; median duration of treatment was 16 weeks.

Study Arms (1)

Carfilzomib Combination

EXPERIMENTAL

Participants received carfilzomib on days 2, 3, 9, and 10 of each 21-day cycle as per the dose escalation schema, carboplatin at a target area under the curve (AUC) of 5 on day 1 of each cycle, and etoposide 100 mg/m² on days 1, 2, 3 of each 21-day cycle for up to 6 cycles. Participants with stable disease or better continued to receive carfilzomib alone until progressive disease (PD), unacceptable toxicity, withdrawal of consent, study closure, or death, whichever occurred earliest.

Drug: Carfilzomib; Drug: Carboplatin; Drug: Etoposide

Interventions

Carfilzomib DRUG

Administered by intravenous infusion.

Also known as: PR-171, PR171, Kyprolis®

Carfilzomib Combination

Carboplatin DRUG

Administered by intravenous infusion.

Carfilzomib Combination

Etoposide DRUG

Administered by intravenous infusion.

Carfilzomib Combination

Eligibility Criteria

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

You may qualify if:

• 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
• Subjects with asymptomatic brain metastases or other central nervous system (CNS) disease at screening/diagnosis are eligible
• Males and females ≥ 18 years of age
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1

You may not qualify if:

• 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.
• 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
• 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

Sponsors & Collaborators

• Amgen: lead

Study Sites (17)

Yale University, Yale Cancer Center

New Haven, Connecticut, United States

Location

UF Health Davis Cancer Pavilion and Shands Med Plaza

Gainesville, Florida, United States

Location

Goshen Center for Cancer Care

Goshen, Indiana, United States

Location

Horizon Oncology Research, Inc.

Lafayette, Indiana, United States

Location

Indiana University Health Ball Memorial Hospital

Muncie, Indiana, United States

Location

Baptist Health Lexington Clinical Research Center

Lexington, Kentucky, United States

Location

Frederick Memorial Hospital

Frederick, Maryland, United States

Location

John Theurer Cancer Center at Hackensack UMC

Hackensack, New Jersey, United States

Location

Levine Cancer Institute

Charlotte, North Carolina, United States

Location

Wake Forest Baptist Health

Winston-Salem, North Carolina, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Location

Juravinski Cancer Centre

Hamilton, Ontario, Canada

Location

Regional Budgetary Healthcare Institution "Kursk Regional Clinical Oncology Dispensary"

Kislino, Kursk Oblast, Russia

Location

State budgetary healthcare institution of Arkhangelsk Region "Arkhangelsk Clinical Oncological Dispensary"

Arkhangelsk, Russia

Location

Federal State Budgetary Scientific Institution "N.N. Blokhin Russian Cancer Research Center"

Moscow, Russia

Location

State Budgetary Educational Inslitution of Higher Professional Education "First St. Petersburg I.P.Pavlov State Medical University"

Saint Petersburg, Russia

Location

State Budgetary Healthcare Institution of Yaroslavl Region "Regional Clinical Oncological Hospital"

Yaroslavl, Russia

Location

MeSH Terms

Conditions

Small Cell Lung Carcinoma

Interventions

carfilzomib; Carboplatin; Etoposide

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)

Coordination Complexes; Organic Chemicals; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 6, 2013
• First Posted: November 19, 2013
• Study Start: November 5, 2013
• Primary Completion: August 1, 2016
• Study Completion: May 4, 2017
• Last Updated: August 28, 2017
• Results First Posted: August 28, 2017

Record last verified: 2017-07

Locations

CA (1); RU (5); US (11)