Study of Amrubicin in Patients With Small Cell Lung Cancer Refractory or Progressive to Prior Therapy

Small Cell Lung Cancer Clinical Trial

Official title:

A Phase 2 Trial of Single-Agent Amrubicin in Patients With Extensive Disease Small Cell Lung Cancer That is Refractory or Progressive Within 90 Days of Completion of First Line Platinum-based Chemotherapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00375193
• Other study ID #: CNF3140-SCLC-002
• Status: Completed
• Phase: Phase 2
• Start date: November 1, 2006
• Est. completion date: March 1, 2009

Study information

• Verified date: October 2019
• Source: Celgene
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of the study is to evaluate the objective tumor response rate of amrubicin when administered as second-line therapy to ED-SCLC patients who have refractory or progressive disease.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 75
• Est. completion date: March 1, 2009
• Est. primary completion date: May 1, 2008
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histological or cytological diagnosis of SCLC; extensive-disease (ED) at time of study entry

• Refractory to first-line platinum-based chemotherapy (i.e., has received one prior platinum-based chemotherapy regimen) defined as one of the following:

• Best response to first-line chemotherapy is radiographically documented progression (refractory disease)

• Best response to first-line chemotherapy is radiographically documented response or stable disease, with subsequent documented progression during continuing chemotherapy (resistant relapse)

• Documented progression within 90 days of completion of first-line chemotherapy (last dose of chemotherapy), regardless of best response to treatment (resistant relapse)

• At least 18 years of age

• ECOG Performance Status of 0, 1, or 2

• Measurable disease defined by RECIST criteria

• Measurable disease: The presence of at least one measurable lesion. If only one lesion is present, the neoplastic nature of the disease site should be confirmed by histology and/or cytology.

• Measurable lesion: Lesions that can be accurately measured in at least one dimension with the longest diameter =20mm using conventional techniques or =10mm using spiral CT scans.

• CT (including spiral CT) scans and MRI are the preferred methods of measurement; however, chest x-rays are acceptable if the lesions are clearly defined and surrounded by aerated lung. Clinically detected lesions will only be considered measurable when they are superficial (e.g., skin nodules and palpable lymph nodes). For the case of skin lesions, documentation by color photography, including a ruler to estimate the size of the lesion is required.

• Adequate organ function including the following:

• Adequate bone marrow reserve: absolute neutrophil (segmented and bands) count (ANC) =1500 cells/µL, platelet count =100,000 cells/µL and hemoglobin =9g/dL.

• Hepatic: bilirubin = 1.5 X ULN; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 3.0 X ULN.

• Renal: serum creatinine < 2.0 mg/dL or calculated creatinine clearance >60 mL/min.

• Cardiac: Left ventricular ejection fraction (LVEF) = 50% by MUGA or echocardiography (intra-patient reassessment of LVEF should be performed via the same method throughout the study).

• Negative serum pregnancy test at the time of enrollment for women of child-bearing potential. For men and women of child-bearing potential, use of effective contraceptive methods during the study.

• Ability to understand the requirements of the study, provide written informed consent and authorization of use and disclosure of protected health information, and agree to abide by the study restrictions and to return for the required assessments.

Exclusion Criteria:

• Pregnant or nursing women

• Chest radiotherapy within the previous 28 days or other radiotherapy within the previous 14 days. Recovery from the acute toxic effects of radiation required prior to study enrollment. Measurable lesions that have been previously irradiated must be enlarging to be considered target lesions. Prior radiation therapy allowed to < 25% of the bone marrow.

• More than 1 prior chemotherapy regiment for SCLC

• Prior anthracycline treatment

• Treatment with any investigational agent within 28 days or standard chemotherapy within 21 days prior to first dose. Patients must have recovered from all acute adverse effecxts of prior therapies, excluding alopecia

• Patients with secondary primary malignancy (except in situ carcinoma of the cervix or adequately treated nonmelanomatous carcinoma of the skin or other malignancy treated at least 2 years previously with surgery and/or radiotherapy and no evidence of recurrence since that time)

• Concurrent severe or uncontrolled medical disease (i.e., active systemic infection, diabetes, hypertension, coronary artery disease, congestive heart failure) that, in the opinion of the Investigator, would compromise the safety of the patient or compromise the ability of the patient to complete the study.

• Symptomatic central nervous system metastases. Patients with asymptomatic brain metastases are allowed. The patient must be stable after radiotherapy for = 2 weeks and off corticosteroids for = 1 week.

• History of interstitial lung disease or pulmonary fibrosis.

Related Conditions & MeSH terms

• Lung Neoplasms
• Small Cell Lung Cancer
• Small Cell Lung Carcinoma

Intervention

Drug:
• Amrubicin
Amrubicin 40mg/m<2> IV days 1, 2, 3 of each 21-day cycle until Cycle 6 or no longer beneficial

Locations

Country	Name	City	State
Netherlands	Free University Medical Center	Amsterdam
United Kingdom	Royal Marsden Hospital in Downs Road	Sutton	Surrey
United States	New York Oncology Hematology, PC	Albany	New York
United States	Texas Oncology - Amarillo	Amarillo	Texas
United States	Mamie McFaddin Ward Cancer Center	Beaumont	Texas
United States	Texas Oncology, PA - Bedford	Bedford	Texas
United States	Maryland Oncology Hematology, PA	Columbia	Maryland
United States	Missouri Cancer Associates	Columbia	Missouri
United States	John B. Amos Cancer Center	Columbus	Georgia
United States	Texas Cancer Center at Medical City	Dallas	Texas
United States	Texas Oncology, P.A. - Dallas	Dallas	Texas
United States	Texas Oncology, P.A., Sammons Cancer Center	Dallas	Texas
United States	Willamette Valley Cancer Center	Eugene	Oregon
United States	Texas Oncology, PA - Fort Worth	Fort Worth	Texas
United States	Northwestern Carolina Oncology & Hematology	Hickory	North Carolina
United States	Central Indiana Cancer Centers - Indianapolis	Indianapolis	Indiana
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	Medical Oncology Associates	Kingston	Pennsylvania
United States	University of Tennessee Medical Center, Knoxville	Knoxville	Tennessee
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	Rocky Mountain Cancer Center - Sky Ridge	Lone Tree	Colorado
United States	Norton Healthcare - Louisville Oncology	Louisville	Kentucky
United States	Minnesota Onc/Hem, PA - Minneapolis	Minneapolis	Minnesota
United States	University of MN/Division of Hematology, Oncology & Transplantation	Minneapolis	Minnesota
United States	Sarah Cannon	Nashville	Tennessee
United States	Cancer Care & Hematology Specialists of Chicago	Niles	Illinois
United States	Virginia Oncology Associates - Norfolk, VA	Norfolk	Virginia
United States	Ocala Oncology Center	Ocala	Florida
United States	Cancer Centers of Florida, PA	Ocoee	Florida
United States	West Texas Cancer Center	Odessa	Texas
United States	Oncology & Hematology of Central Illinois	Peoria	Illinois
United States	Hematology Oncology Associates	Phoenix	Arizona
United States	Blessing Cancer Center	Quincy	Illinois
United States	Raleigh Hematology Oncology Associates	Raleigh	North Carolina
United States	St. Joseph Oncology, Inc.	Saint Joseph	Missouri
United States	Arch Medical Group - Arch Medical Services, Inc.	Saint Louis	Missouri
United States	Oncology & Hematology Associates of Southwest Virginia, Inc.	Salem	Virginia
United States	Puget Sound Cancer Center	Seattle	Washington
United States	SUNY Upstate Medical Center	Syracuse	New York
United States	Tyler Cancer Center	Tyler	Texas
United States	Northwest Cancer Specialists - Vancouver Cancer Center	Vancouver	Washington
United States	Texas Oncology Cancer Care and Research Center	Waco	Texas
United States	Texas Oncology, PA - Deke Slayton Cancer Center	Webster	Texas
United States	Alliance Hematology Oncology, PA - Carroll County Cancer Center	Westminster	Maryland
United States	Texas Oncology - Wichita Falls	Wichita Falls	Texas
United States	Yakima Regional Cancer Care Center - North Star Lodge Cancer Center	Yakima	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Celgene

Countries where clinical trial is conducted

United States,  Netherlands,  United Kingdom, 

References & Publications (2)

Ettinger DS, Jotte R, Lorigan P, Gupta V, Garbo L, Alemany C, Conkling P, Spigel DR, Dudek AZ, Shah C, Salgia R, McNally R, Renschler MF, Oliver JW. Phase II study of amrubicin as second-line therapy in patients with platinum-refractory small-cell lung cancer. J Clin Oncol. 2010 May 20;28(15):2598-603. doi: 10.1200/JCO.2009.26.7682. Epub 2010 Apr 12. — View Citation

Spigel DR, et al. Amrubicin (AMR) and cardiotoxicity in second-line treatment of small cell lung cancer (SCLC): A pooled analysis of left ventricular ejection fraction (LVEF) in two phase II trials. 2009 ASCO Annual Meeting, May 29-June 2, 2009, Chicago, IL. Abstract No.e19019. J Clin Oncol 2009;27(suppl)

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective tumor response rate according to RECIST		Until Disease Progression
Secondary	Duration of overall response		Until Disease Progression
Secondary	Time to tumor progression		Until Disease Progression
Secondary	Progression free survival		Until death or disease progression
Secondary	Overall survival		Until death
Secondary	Toxicity profile		Until 30 days after final dose
Secondary	Incidence of cardiomyopathy		Until end of study participation
Secondary	Incidence of CNS progression		Until disease progression
Secondary	Pharmacokinetic parameters		Cycle 1 only