Clinical trial NCT00375193: Study of Amrubicin in Patients With Small Cell Lung Cancer Refractory or Progressive to Prior Therapy
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Small Cell Lung Cancer
Keywords: small cell lung cancer
amrubicin
Lead sponsor: Celgene
Sponsor class: INDUSTRY
First posted: 2006-09-12
Enrollment: 75
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Objective tumor response rate according to RECIST
timeFrame: Until Disease Progression
Secondary outcomes:
measure: Duration of overall response
timeFrame: Until Disease Progression
measure: Time to tumor progression
timeFrame: Until Disease Progression
measure: Progression free survival
timeFrame: Until death or disease progression
measure: Overall survival
timeFrame: Until death
measure: Toxicity profile
timeFrame: Until 30 days after final dose
measure: Incidence of cardiomyopathy
timeFrame: Until end of study participation
measure: Incidence of CNS progression
timeFrame: Until disease progression
measure: Pharmacokinetic parameters
timeFrame: Cycle 1 only
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Hematology Oncology Associates
state: Arizona
city: Lone Tree
country: United States
facility: Rocky Mountain Cancer Center - Sky Ridge
state: Colorado
city: Ocala
country: United States
facility: Ocala Oncology Center
state: Florida
city: Ocoee
country: United States
facility: Cancer Centers of Florida, PA
state: Florida
city: Columbus
country: United States
facility: John B. Amos Cancer Center
state: Georgia
city: Niles
country: United States
facility: Cancer Care & Hematology Specialists of Chicago
state: Illinois
city: Peoria
country: United States
facility: Oncology & Hematology of Central Illinois
state: Illinois
city: Quincy
country: United States
facility: Blessing Cancer Center
state: Illinois
city: Indianapolis
country: United States
facility: Central Indiana Cancer Centers - Indianapolis
state: Indiana
city: Louisville
country: United States
facility: Norton Healthcare - Louisville Oncology
state: Kentucky
city: Columbia
country: United States
facility: Maryland Oncology Hematology, PA
state: Maryland
city: Westminster
country: United States
facility: Alliance Hematology Oncology, PA - Carroll County Cancer Center
state: Maryland
city: Kalamazoo
country: United States
facility: West Michigan Cancer Center
state: Michigan
city: Minneapolis
country: United States
facility: Minnesota Onc/Hem, PA - Minneapolis
state: Minnesota
city: Minneapolis
country: United States
facility: University of MN/Division of Hematology, Oncology & Transplantation
state: Minnesota
city: Columbia
country: United States
facility: Missouri Cancer Associates
state: Missouri
city: Saint Joseph
country: United States
facility: St. Joseph Oncology, Inc.
state: Missouri
city: Saint Louis
country: United States
facility: Arch Medical Group - Arch Medical Services, Inc.
state: Missouri
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Albany
country: United States
facility: New York Oncology Hematology, PC
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical Center
state: New York
city: Hickory
country: United States
facility: Northwestern Carolina Oncology & Hematology
state: North Carolina
city: Raleigh
country: United States
facility: Raleigh Hematology Oncology Associates
state: North Carolina
city: Eugene
country: United States
facility: Willamette Valley Cancer Center
state: Oregon
city: Kingston
country: United States
facility: Medical Oncology Associates
state: Pennsylvania
city: Knoxville
country: United States
facility: University of Tennessee Medical Center, Knoxville
state: Tennessee
city: Nashville
country: United States
facility: Sarah Cannon
state: Tennessee
city: Amarillo
country: United States
facility: Texas Oncology - Amarillo
state: Texas
city: Beaumont
country: United States
facility: Mamie McFaddin Ward Cancer Center
state: Texas
city: Bedford
country: United States
facility: Texas Oncology, PA - Bedford
state: Texas
city: Dallas
country: United States
facility: Texas Cancer Center at Medical City
state: Texas
city: Dallas
country: United States
facility: Texas Oncology, P.A. - Dallas
state: Texas
city: Dallas
country: United States
facility: Texas Oncology, P.A., Sammons Cancer Center
state: Texas
city: Fort Worth
country: United States
facility: Texas Oncology, PA - Fort Worth
state: Texas
city: Odessa
country: United States
facility: West Texas Cancer Center
state: Texas
city: Tyler
country: United States
facility: Tyler Cancer Center
state: Texas
city: Waco
country: United States
facility: Texas Oncology Cancer Care and Research Center
state: Texas
city: Webster
country: United States
facility: Texas Oncology, PA - Deke Slayton Cancer Center
state: Texas
city: Wichita Falls
country: United States
facility: Texas Oncology - Wichita Falls
state: Texas
city: Norfolk
country: United States
facility: Virginia Oncology Associates - Norfolk, VA
state: Virginia
city: Salem
country: United States
facility: Oncology & Hematology Associates of Southwest Virginia, Inc.
state: Virginia
city: Seattle
country: United States
facility: Puget Sound Cancer Center
state: Washington
city: Vancouver
country: United States
facility: Northwest Cancer Specialists - Vancouver Cancer Center
state: Washington
city: Yakima
country: United States
facility: Yakima Regional Cancer Care Center - North Star Lodge Cancer Center
state: Washington
city: Amsterdam
country: Netherlands
facility: Free University Medical Center
city: Sutton
country: United Kingdom
facility: Royal Marsden Hospital in Downs Road
state: Surrey
Study officials:
affiliation: Theradex
name: Richard S Ungerleider, MD
role: STUDY_DIRECTOR
References:
citation: 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.
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)