Albumin-bound Paclitaxel (ABI-007) for Patients With Advanced Non-Small Cell Lung Cancer

Non-Small Cell Lung Carcinoma Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00540514
• Other study ID #: CA031
• Status: Completed
• Phase: Phase 3
• Start date: November 1, 2007
• Est. completion date: February 1, 2013

Study information

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

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1052
• Est. completion date: February 1, 2013
• Est. primary completion date: October 1, 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 [ßhCG]) 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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-Small Cell Lung Carcinoma

Intervention

Drug:
• Albumin-bound paclitaxel
Administered by intravenous infusion.
• Paclitaxel
Administered by intravenous infusion.
• Carboplatin
Administered by intravenous infusion. Dosing was based on the Calvert formula: carboplatin dose (mg) = (Target AUC) x (glomerular filtration rate [GFR] + 25). For the purposes of this protocol, the GFR is considered to be equivalent to creatinine clearance (calculated by the method of Cockcroft and Gault, 1976).

Locations

Country	Name	City	State
Canada	William Osler Health Centre, Brampton Clinic	Brampton	Ontario
Canada	Hopital du Sacre-Coeur de Montreal	Montreal	Quebec
Canada	McGill University- Dept. of Oncology	Montreal	Quebec
Canada	Royal Columbian Hospital	New Westminster	British Columbia
Canada	Princess Margaret Hospital	Toronto	Ontario
Canada	Toronto East General Hospital	Toronto	Ontario
United States	Cancer Outreach Associates, PC	Abingdon	Virginia
United States	Phoebe Cancer Center	Albany	Georgia
United States	Pacific Cancer Medical Center, Inc.	Anaheim	California
United States	Comprehensive Blood and Cancer Center	Bakersfield	California
United States	Mercy Medical Center	Baltimore	Maryland
United States	Essex Oncology of North Jersey	Belleville	New Jersey
United States	Fletcher Allen Health Care	Burlington	Vermont
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Mary Imogene Bassett Hospital	Cooperstown	New York
United States	Dallas Oncology Consultants, PA	Duncanville	Texas
United States	Southwest Cancer Care	Escondido	California
United States	The Center for Cancers and Blood Disorders	Fort Worth	Texas
United States	Robert A. Moss, MD, FACP, Inc.	Fountain Valley	California
United States	Genesis Cancer Center- Hot Springs	Hot Springs	Arkansas
United States	Clearview Cancer Institute Oncology Specialties, P.C.	Huntsville	Alabama
United States	St. Mary Medical Center- Oncology, Hematology PC	Langhorne	Pennsylvania
United States	Little Rock Hematology Oncology Associates	Little Rock	Arkansas
United States	Pacific Shores Medical Group	Long Beach	California
United States	Kentuckiana Cancer Institute, PLLC	Louisville	Kentucky
United States	Joe Arrington Cancer Research and Treatment Center	Lubbock	Texas
United States	Ventura County Hematology-Oncology Specialists	Oxnard	California
United States	Comprehensice Cancer Ctr.	Palms Springs	California
United States	Mercy Hospital	Portland	Maine
United States	St. Louis University	Saint Louis	Missouri
United States	Gulf Coast Oncology Associates	Saint Petersburg	Florida
United States	Maine Center for Cancer Medicine	Scarborough	Maine
United States	Lake County Oncology and Hematology, PA	Tavares	Florida
United States	Blood and Cancer Center of East Texas	Tyler	Texas
United States	Tyler Hematology Oncology	Tyler	Texas
United States	Cancer Center of Kansas	Wichita	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Celgene

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (8)

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 f — View 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. Review. — View 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. — View 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. — View 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 — View 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 — View 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®-paclitaxel in combination with carboplatin as first-line therapy in elderly patients with advanced non-small-cell l — View 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 no — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Percentage of Participants Who Achieved an Objective Confirmed Complete Response or Partial Response by Blinded Radiology Assessment, by Histology	Antitumor response was defined as the percentage of participants who achieved an objective response (Confirmed Response [CR] or Partial Response [PR]), confirmed by repeat assessments performed no less than 4 weeks after the criteria for response were first met. Response was based on the blinded radiological review using Response Evaluation Criteria in Solid Tumors (RECIST) response guidelines, Version 1.0.; A complete response was defined as a disappearance of all target and non-target lesions and no new lesions.; Partial response was defined as = 30% decrease in the sum of the longest diameters (SLD) of target lesions, taking as reference the baseline SLD, and the persistence of one or more non-target lesions not qualifying for CR or Progressive Disease (the "unequivocal progression" of existing non-target lesion(s) or appearance of one or more new lesions).; Histology was determined at the time of primary diagnosis.	Objective response was evaluated every 6 weeks until progression or new anti-cancer therapy initiation, up to 22 months.
Other	Maximal Degree of Anemia Based on Clinical Laboratory Values for Hemoglobin	The maximal degree of anemia (and myelosuppression) was assessed by the overall nadir of hemoglobin levels based on clinical laboratory measurements graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0.	38 months
Other	Maximal Degree of Neutropenia Based on Clinical Laboratory Values of Absolute Neutrophil Count	The maximal degree of neutropenia (and myelosuppression) was assessed by the overall nadir of absolute neutrophil count (ANC) based on clinical laboratory measurements graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0.	38 months
Other	Maximal Degree of Thrombocytopenia Based on Clinical Laboratory Values of Platelet Count	The maximal degree of thrombocytopenia (and myelosuppression) was assessed by the overall nadir of platelet count based on clinical laboratory measurements graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0.	38 months
Other	Time to Improvement of = Grade 3 Treatment Related Peripheral Neuropathy	Peripheral neuropathy was graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 on the following scale: Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life-threatening, Grade 5 = death.; Improvement in peripheral neuropathy was evaluated as: Time to improvement of grade 3 or higher peripheral neuropathy by at least one grade; Time to improvement of grade 3 or higher peripheral neuropathy to grade 1.; Time to improvement was defined as the time from the first occurrence of grade 3 or higher treatment related neuropathy to improvement, as defined. Participants not experiencing improvement were censored at the last time the participant was evaluated for adverse events.	38 months
Primary	Percentage of Participants Who Achieved an Objective Confirmed Complete Response or Partial Response by Blinded Radiology Assessment	Antitumor response was defined as the percentage of participants who achieved an objective response (Confirmed Response [CR] or Partial Response [PR]), confirmed by repeat assessments performed no less than 4 weeks after the criteria for response were first met. Response was based on the blinded radiological review using Response Evaluation Criteria in Solid Tumors (RECIST) response guidelines, Version 1.0.; A complete response was defined as a disappearance of all target and non-target lesions and no new lesions.; Partial response was defined as = 30% decrease in the sum of the longest diameters (SLD) of target lesions, taking as reference the baseline SLD, and the persistence of one or more non-target lesions not qualifying for CR or Progressive Disease (the "unequivocal progression" of existing non-target lesion(s) or appearance of one or more new lesions).	Objective response was evaluated every 6 weeks until progression or new anti-cancer therapy initiation, up to 22 months.
Secondary	Progression-free Survival by Blinded Radiology Assessment	Progression free survival time was defined as the time from the day of randomization to the start of disease progression or death (any cause), whichever occurred first, based on the blinded radiological review response assessment. Progressive disease was defined as a = 20% increase in the SLD of target lesions, taking as reference the nadir SLD recorded since the treatment started, or the presence of one or more new lesions, or the "unequivocal progression" of existing non-target lesion(s) or appearance of one or more new lesion(s).; Participants who did not have disease progression or had not died were censored at the last visit they were documented as progression free. If palliative radiotherapy or surgery at lesion sites occurred, the participant was censored at the last date without documented progression prior to radiotherapy or surgery. In follow-up, participants who began new therapy prior to progression were censored at the last documented date as progression-free.	Assessed every 6 weeks until progression or death, up to 38 months
Secondary	Overall Participant Survival	Overall survival was defined as the time from the day of randomization to participant death (due to any cause), as assessed by post study follow-up performed monthly for 6 months and every 3 months thereafter for 12 months. All participants who were lost to the follow-up prior to the end of the trial or who completed the 18 month follow up phase were censored at last known time the participant was alive.	Up to 38 months
Secondary	Percentage of Participants With Controlled Disease	Controlled disease was defined as the percentage of participants with stable disease for = 16 weeks or confirmed complete or partial overall response, based on blinded radiological assessment. Stable disease was defined as neither sufficient shrinkage of target lesions to qualify for Partial Response, nor sufficient increase to qualify for Progressive Disease, or the persistence of one or more non-target lesions not qualifying for Complete Response or Progressive Disease.	Assessed every 6 weeks, up to 22 months
Secondary	Duration of Response in Responding Patients	Duration of response was assessed by progression free survival for participants who achieved a confirmed complete response or partial response based on blinded radiological assessment.	Assessed every 6 weeks, up to 38 months
Secondary	Number of Participants With Adverse Events (AEs)	A Treatment-emergent AE was any AE that began or worsened in grade after the start of study drug through 30 days after the last dose of study drug or end of study whichever is later. Treatment related toxicity was one considered by the investigator to be possibly, probably or definitely related to study drug. AEs were graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v3.0 on the following scale: Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life-threatening, Grade 5 = death. A serious adverse event (SAE) is any untoward medical occurrence at any dose that: is fatal or life-threatening; results in persistent or significant disability or incapacity; requires or prolongs in-patient hospitalization; is a congenital anomaly/birth defect in the offspring of a patient; and conditions not included in the above that may jeopardize the patient or may require intervention to prevent one of the outcomes listed above.	Up to 38 months
Secondary	Pharmacokinetic (PK) Parameters		Blood samples for PK analyses were taken during Cycle 1 at 0.25, 3.5 and 24 hours post-infusion.
Secondary	SPARC Status and Correlation With Overall Survival	The expression and cellular distribution of Secreted Protein Acidic and Rich in cysteine (SPARC) in biopsies of lung tumor was examined by immunohistochemistry using a 2 antibody system by an approved central laboratory and analyzed by 2 pathologists. The following tissue components were scored: tumor cells, fibroblasts, inflammatory cells, acellular stroma/matrix, and blood vessels.; To classify participants into "high-SPARC" and "low-SPARC" groups, an average z-score was calculated across variables and classified "high-SPARC" (average z-scores =0) and "low-SPARC" (average z-scores <0) groups.; SPARC status was then correlated with overall survival (the time from the day of randomization to participant death due to any cause).	Archival tissue samples were used for SPARC analysis. Survival was assessed for up to 38 months.