Clinical trial NCT00540514: Albumin-bound Paclitaxel (ABI-007) for Patients With Advanced Non-Small Cell Lung Cancer
Official title: A Randomized, Phase III Trial of ABI-007 and Carboplatin Compared With Taxol and Carboplatin as First-Line Therapy in Patients With Advanced Non-Small Cell Lung Cancer (NSCLC)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Non-Small Cell Lung Carcinoma
Keywords: Advanced Non-Small Cell Lung Cancer
Lead sponsor: Celgene
Sponsor class: INDUSTRY
First posted: 2007-10-08
Enrollment: 1052
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to compare disease response of Albumin-bound paclitaxel (ABI-007) plus Carboplatin versus Taxol and Carboplatin as first-line therapy in patients with advanced non-small cell lung cancer (NSCLC).


Eligibility criteria: Inclusion Criteria:

* Histologically or cytologically confirmed stage IIIB or IV non-small cell lung cancer (NSCLC)
* Male or non-pregnant and non-lactating female, and equal or greater than age 18

  * If a female patient is of child-bearing potential, as evidence by regular menstrual periods, she must have a negative serum pregnancy test (beta human chorionic gonadotropin \[βhCG\]) documented within 72 hours of the first administration of study drug
  * If sexually active, the patient must agree to utilize contraception considered adequate and appropriate by the investigator
* No other current active malignancy
* Radiographically-documented measurable disease (defined by the presence of at least 1 radiographically documented measurable lesion)
* Patients must have received no prior chemotherapy for the treatment of metastatic disease. Adjuvant chemotherapy permitted providing cytotoxic chemotherapy was completed 12 months prior to starting the study
* Patient has the following blood counts at baseline:

  * Absolute neutrophil count (ANC) greater than or equal to 1.5x10\^9/L
  * Platelets greater than or equal to 100x10\^9/L
  * Hemoglobin (Hgb) greater than or equal to 9 g/dL
* Patient has the following blood chemistry levels at baseline:

  * Aspartate aminotransferase (SGOT), alanine aminotransferase (SGPT) less than or equal to 2.5 x upper limit of normal range (ULN) or less than or equal to 5.0 x ULN if liver metastases;
  * Total bilirubin less than or equal to ULN
  * Creatinine less than or equal to 1.5 mg/dL
* Expected survival of greater than 12 weeks
* Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
* Patient or his/her legally authorized representative or guardian has been informed about the nature of the study, and has agreed to participate in the study, and signed the Informed Consent form prior to participation in any study-related activities

Exclusion Criteria:

* Evidence of active brain metastases, including leptomeningeal involvement. Prior evidence of brain metastasis permitted only if treated and stable and off therapy for greater than or equal to 1 month
* The only evidence of disease is non-measurable
* Patient has pre-existing peripheral neuropathy of Grade 2, 3, or 4 (per Common Terminology Criteria for Adverse Events \[CTCAE\] Version 3).
* Patient received radiotherapy in the last 4 weeks, except if to a non-target lesion only. Prior radiation to a target lesion is permitted only if there has been clear progression of the lesion since radiation was completed
* Patient has a clinically significant concurrent illness
* Patient has received treatment with any investigational drug within the previous 4 weeks
* Patient has a history of allergy or hypersensitivity to any of the study drugs
* Patient has serious medical risk factors involving any of the major organ systems such that the investigator considers it unsafe for the patient to receive an experimental research drug
* Patient is enrolled in any other clinical protocol or investigational trial that involves administration of experimental therapy and/or therapeutic devices.

Primary outcomes:
measure: Percentage of Participants Who Achieved an Objective Confirmed Complete Response or Partial Response by Blinded Radiology Assessment
timeFrame: Objective response was evaluated every 6 weeks until progression or new anti-cancer therapy initiation, up to 22 months.
Secondary outcomes:
measure: Progression-free Survival by Blinded Radiology Assessment
timeFrame: Assessed every 6 weeks until progression or death, up to 38 months
measure: Overall Participant Survival
timeFrame: Up to 38 months
measure: Percentage of Participants With Controlled Disease
timeFrame: Assessed every 6 weeks, up to 22 months
measure: Duration of Response in Responding Patients
timeFrame: Assessed every 6 weeks, up to 38 months
measure: Number of Participants With Adverse Events (AEs)
timeFrame: Up to 38 months
measure: Pharmacokinetic (PK) Parameters
timeFrame: Blood samples for PK analyses were taken during Cycle 1 at 0.25, 3.5 and 24 hours post-infusion.
measure: SPARC Status and Correlation With Overall Survival
timeFrame: Archival tissue samples were used for SPARC analysis. Survival was assessed for up to 38 months.
Other outcomes:
measure: Percentage of Participants Who Achieved an Objective Confirmed Complete Response or Partial Response by Blinded Radiology Assessment, by Histology
timeFrame: Objective response was evaluated every 6 weeks until progression or new anti-cancer therapy initiation, up to 22 months.
measure: Maximal Degree of Anemia Based on Clinical Laboratory Values for Hemoglobin
timeFrame: 38 months
measure: Maximal Degree of Neutropenia Based on Clinical Laboratory Values of Absolute Neutrophil Count
timeFrame: 38 months
measure: Maximal Degree of Thrombocytopenia Based on Clinical Laboratory Values of Platelet Count
timeFrame: 38 months
measure: Time to Improvement of ≥ Grade 3 Treatment Related Peripheral Neuropathy
timeFrame: 38 months
Locations:
city: Huntsville
country: United States
facility: Clearview Cancer Institute Oncology Specialties, P.C.
state: Alabama
city: Hot Springs
country: United States
facility: Genesis Cancer Center- Hot Springs
state: Arkansas
city: Little Rock
country: United States
facility: Little Rock Hematology Oncology Associates
state: Arkansas
city: Anaheim
country: United States
facility: Pacific Cancer Medical Center, Inc.
state: California
city: Bakersfield
country: United States
facility: Comprehensive Blood and Cancer Center
state: California
city: Escondido
country: United States
facility: Southwest Cancer Care
state: California
city: Fountain Valley
country: United States
facility: Robert A. Moss, MD, FACP, Inc.
state: California
city: Long Beach
country: United States
facility: Pacific Shores Medical Group
state: California
city: Oxnard
country: United States
facility: Ventura County Hematology-Oncology Specialists
state: California
city: Palms Springs
country: United States
facility: Comprehensice Cancer Ctr.
state: California
city: Saint Petersburg
country: United States
facility: Gulf Coast Oncology Associates
state: Florida
city: Tavares
country: United States
facility: Lake County Oncology and Hematology, PA
state: Florida
city: Albany
country: United States
facility: Phoebe Cancer Center
state: Georgia
city: Wichita
country: United States
facility: Cancer Center of Kansas
state: Kansas
city: Louisville
country: United States
facility: Kentuckiana Cancer Institute, PLLC
state: Kentucky
city: Portland
country: United States
facility: Mercy Hospital
state: Maine
city: Scarborough
country: United States
facility: Maine Center for Cancer Medicine
state: Maine
city: Baltimore
country: United States
facility: Mercy Medical Center
state: Maryland
city: Saint Louis
country: United States
facility: St. Louis University
state: Missouri
city: Belleville
country: United States
facility: Essex Oncology of North Jersey
state: New Jersey
city: Cooperstown
country: United States
facility: Mary Imogene Bassett Hospital
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Langhorne
country: United States
facility: St. Mary Medical Center- Oncology, Hematology PC
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Duncanville
country: United States
facility: Dallas Oncology Consultants, PA
state: Texas
city: Fort Worth
country: United States
facility: The Center for Cancers and Blood Disorders
state: Texas
city: Lubbock
country: United States
facility: Joe Arrington Cancer Research and Treatment Center
state: Texas
city: Tyler
country: United States
facility: Blood and Cancer Center of East Texas
state: Texas
city: Tyler
country: United States
facility: Tyler Hematology Oncology
state: Texas
city: Burlington
country: United States
facility: Fletcher Allen Health Care
state: Vermont
city: Abingdon
country: United States
facility: Cancer Outreach Associates, PC
state: Virginia
city: New Westminster
country: Canada
facility: Royal Columbian Hospital
state: British Columbia
city: Brampton
country: Canada
facility: William Osler Health Centre, Brampton Clinic
state: Ontario
city: Toronto
country: Canada
facility: Toronto East General Hospital
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
city: Montreal
country: Canada
facility: McGill University- Dept. of Oncology
state: Quebec
city: Montreal
country: Canada
facility: Hopital du Sacre-Coeur de Montreal
state: Quebec
Study officials:
affiliation: University of North Carolina, Chapel Hill
name: Mark A Socinski, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hirsh V. nab-paclitaxel for the management of patients with advanced non-small-cell lung cancer. Expert Rev Anticancer Ther. 2014 Feb;14(2):129-41. doi: 10.1586/14737140.2014.881719.
citation: Langer CJ, Hirsh V, Ko A, Renschler MF, Socinski MA. Weekly nab-paclitaxel in combination with carboplatin as first-line therapy in patients with advanced non-small-cell lung cancer: analysis of safety and efficacy in patients with renal impairment. Clin Lung Cancer. 2015 Mar;16(2):112-20. doi: 10.1016/j.cllc.2014.09.003. Epub 2014 Sep 30.
citation: Langer CJ, Hirsh V, Okamoto I, Lin FJ, Wan Y, Whiting S, Ong TJ, Renschler MF, Botteman MF. Survival, quality-adjusted survival, and other clinical end points in older advanced non-small-cell lung cancer patients treated with albumin-bound paclitaxel. Br J Cancer. 2015 Jun 30;113(1):20-9. doi: 10.1038/bjc.2015.181. Epub 2015 Jun 2.
citation: Socinski MA, Bondarenko I, Karaseva NA, Makhson AM, Vynnychenko I, Okamoto I, Hon JK, Hirsh V, Bhar P, Zhang H, Iglesias JL, Renschler MF. Weekly nab-paclitaxel in combination with carboplatin versus solvent-based paclitaxel plus carboplatin as first-line therapy in patients with advanced non-small-cell lung cancer: final results of a phase III trial. J Clin Oncol. 2012 Jun 10;30(17):2055-62. doi: 10.1200/JCO.2011.39.5848. Epub 2012 Apr 30.
citation: Socinski MA, Langer CJ, Okamoto I, Hon JK, Hirsh V, Dakhil SR, Page RD, Orsini J, Zhang H, Renschler MF. Safety and efficacy of weekly nab(R)-paclitaxel in combination with carboplatin as first-line therapy in elderly patients with advanced non-small-cell lung cancer. Ann Oncol. 2013 Feb;24(2):314-321. doi: 10.1093/annonc/mds461. Epub 2012 Nov 2.
citation: Satouchi M, Okamoto I, Sakai H, Yamamoto N, Ichinose Y, Ohmatsu H, Nogami N, Takeda K, Mitsudomi T, Kasahara K, Negoro S. Efficacy and safety of weekly nab-paclitaxel plus carboplatin in patients with advanced non-small cell lung cancer. Lung Cancer. 2013 Jul;81(1):97-101. doi: 10.1016/j.lungcan.2013.02.020. Epub 2013 Mar 30.
citation: Socinski MA, Okamoto I, Hon JK, Hirsh V, Dakhil SR, Page RD, Orsini J, Yamamoto N, Zhang H, Renschler MF. Safety and efficacy analysis by histology of weekly nab-paclitaxel in combination with carboplatin as first-line therapy in patients with advanced non-small-cell lung cancer. Ann Oncol. 2013 Sep;24(9):2390-6. doi: 10.1093/annonc/mdt235. Epub 2013 Jul 10.
citation: Hirsh V, Okamoto I, Hon JK, Page RD, Orsini J, Sakai H, Zhang H, Renschler MF, Socinski MA. Patient-reported neuropathy and taxane-associated symptoms in a phase 3 trial of nab-paclitaxel plus carboplatin versus solvent-based paclitaxel plus carboplatin for advanced non-small-cell lung cancer. J Thorac Oncol. 2014 Jan;9(1):83-90. doi: 10.1097/JTO.0000000000000011.