The purpose of this study is to determine whether combining ganetespib (STA-9090) with docetaxel is more effective than docetaxel alone in the treatment of patients with advanced non-small cell lung cancer.
Preliminary signals of clinical activity of ganetespib as a single agent have been observed in patients with advanced NSCLC. A Phase 2b/3 Study (9090-08) was initiated to evaluate the safety and activity of ganetespib in combination with docetaxel vs. docetaxel alone in NSCLC. Study 9090-08 is ongoing. Results from an interim analysis show that the combination has been well tolerated and an encouraging improvement in efficacy, including overall survival (OS) has been observed. Update: An independent data monitoring committee (DMC) was established to review accumulating unblinded safety data, and efficacy data at two specified Interim Analyses. The DMC monitored the conduct of the trial (including the accrual/retention of patients) and reviewed the risks and benefits. The study was stopped after the first Interim Analysis due to futility. The efficacy portion of this report is based on a 05 October 2015 data cut after the number of protocol-defined death events (336) for the first interim analysis had been achieved. The safety portion is based on the final database locked on 23 December 2015.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
696
Docetaxel, 75 mg/m\^2, was administered according to prevailing practice and Investigator decision, generally until disease progression, intolerability, or patient's withdrawal of consent.
Ganetespib, 150 mg/m\^2, was administered with docetaxel. After docetaxel treatment ceased, participants whose disease has not progressed continued to receive ganetespib alone until disease progression, unacceptable toxicity, or patient's withdrawal of consent.
Overall Survival as of 19 October 2015
Overall survival (OS) was measured from the date of randomization to the date of death from any cause.
Time frame: up to 36 months
Progression-free Survival (PFS) as of 19 October 2015
The progression-free interval is the interval from the date of randomization until tumor progression per modified Response Evaluation Criteria in Solid Tumors (RECIST 1.1), clinical progression, or death from any cause in the absence of progressive disease, whichever occurs first. Data represents the investigator's assessment. Progressive Disease (PD) was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Time frame: up to 36 months
Overall Survival (OS) In Participants With an Elevated Screening Lactate Dehydrogenase (eLDH) as of 19 October 2015
OS was measured from the date of randomization to the date of death from any cause. Elevated LDH includes values above the upper limit of normal.
Time frame: up to 36 months
Objective Response Rate (ORR) as of 19 October 2015
Percentage of participants whose best overall response, as determined by the investigator using Response Evaluation Criteria in Solid Tumors (RECIST 1.1), was either a complete response (CR) or a partial response (PR). CR was defined as the disappearance (or normalization) of all target lesions. PR was defined as at least 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum of diameters.
Time frame: up to 36 months
Disease Control Rate (DCR) as of 19 October 2015
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Arizona Oncology Associates PC- NAHOA
Flagstaff, Arizona, United States
Arizona Oncology Associates, PC- NAHOA
Prescott Valley, Arizona, United States
Northern Arizona Hematology & Oncology Associates
Sedona, Arizona, United States
Arizona Clinical Research Center, Inc.
Tucson, Arizona, United States
Pacific Cancer Medical Center, Inc
Anaheim, California, United States
Comprehensive Blood & Cancer Center
Bakersfield, California, United States
City of Hope Comprehensive Breast Cancer Center
Duarte, California, United States
UC San Diego Moores Cancer Center
La Jolla, California, United States
Loma Linda University Cancer Center
Loma Linda, California, United States
VA Greater Los Angeles Healthcare System
Los Angeles, California, United States
...and 257 more locations
Percentage of participants whose best overall response, as determined by the investigator using Response Evaluation Criteria in Solid Tumors (RECIST 1.1), was either a complete response (CR), a partial response (PR), or stable disease (SD). CR was defined as the disappearance (or normalization) of all target lesions. PR was defined as at least 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum of diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum of diameters while on study. For participants with a best response of SD, duration of SD must be for at least 6 weeks or 12 weeks.
Time frame: up to 36 months
Kaplan-Meier Estimate of Duration of Response (DOR) as of 19 October 2015
Only participants who achieved a confirmed response (complete response (CR) or partial response (PR)) were included in the DOR analysis. CR was defined as the disappearance (or normalization) of all target lesions. PR was defined as at least 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum of diameters.
Time frame: up to 36 months
Progression Free Survival (PFS) in Participants With an Elevated Screening Lactate Dehydrogenase (eLDH) as of 19 October 2015
The progression-free interval is the interval from the date of randomization until tumor progression per modified Response Evaluation Criteria in Solid Tumors (RECIST 1.1), clinical progression, or death from any cause in the absence of progressive disease, whichever occurs first. Data represents the investigator's assessment. Progressive Disease (PD) was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Elevated LDH includes values above the upper limit of normal.
Time frame: up to 36 months
Objective Response Rate (ORR) in Participants With an Elevated Screening Lactate Dehydrogenase (eLDH) as of 19 October 2015
Percentage of participants whose best overall response, as determined by the investigator using Response Evaluation Criteria in Solid Tumors (RECIST 1.1), was either a complete response (CR) or a partial response (PR). CR was defined as the disappearance (or normalization) of all target lesions. PR was defined as at least 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum of diameters. Elevated LDH includes values above the upper limit of normal. This study stopped prematurely due to futility and development of this product ceased. The sponsor made a decision at that time to not analyze this outcome. The sponsor no longer has staff or capabilities for further analysis.
Time frame: up to 36 months
Disease Control Rate (DCR) in Participants With an Elevated Screening Lactate Dehydrogenase (eLDH) as of 19 October 2015
Percentage of participants whose best overall response, as determined by the investigator using Response Evaluation Criteria in Solid Tumors (RECIST 1.1), was a complete response (CR), a partial response (PR), or stable disease (SD). CR was defined as the disappearance (or normalization) of all target lesions. PR was defined as \<=30% decrease in the sum of diameters of target lesions taking as reference the baseline sum of diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum of diameters while on study. The duration of SD must be for at least 6 weeks or 12 weeks. Elevated LDH includes values above the upper limit of normal. This study stopped prematurely due to futility and development of this product ceased. The sponsor made a decision at that time to not analyze this outcome. The sponsor no longer has staff or capabilities for further analysis.
Time frame: up to 36 months
Kaplan-Meier Estimate for Time to Emergence of New Metastatic Lesion (TNL) as of 19 October 2015
TNL was defined as time from the randomization date to the first day of radiological progression that included new metastatic lesions. Participants with no new metastatic lesions were censored at the date of the most recent radiological assessment.
Time frame: up to 36 months
Percentage of Participants With Progressive Disease Due to Any New Metastatic Lesion as of 19 October 2015
Progressive disease was due to either new metastatic lesions only or new metastatic lesions and target tumor growth.
Time frame: up to 36 months
Participants With Treatment-Emergent Adverse Events as of 23 December 2015
Treatment-emergent adverse events (AEs) were defined as AEs that occurred from the time of first dose through 30 days after the last dose of study medication. The Investigator graded the severity of AEs according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria: Grade 1 = Mild Grade 2 = Moderate Grade 3 = Severe Grade 4 = Life threatening Grade 5 = Death A Serious AE (SAE) is defined as any AE which results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or constitutes an important medical event.
Time frame: up to 36 months
Patient-Reported Quality of Life as Measured by the European Quality Of Life - Five Dimensions - Three Levels (EQ-5D-3L) Survey
The EQ-5D-3L descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels: no problems, some problems, extreme problems. An overall EQ-5D-3L index was calculated (see EuroQoL website, http://www.euroqol.org/eq-5d-products/eq-5d-3l.html), with an index of 1.0 representing full health and and "0" represents dead, with some health states being worse than dead (\<"0"). This study stopped prematurely due to futility and development of this product ceased. The sponsor made a decision at that time to not analyze this outcome. The sponsor no longer has staff or capabilities for further analysis.
Time frame: Day 1 (pre-treatment), Day 63 (Cycle 3 Day 1), Day 105 (Cycle 5 Day 1) and end of trial
Patient-Reported Symptom Improvement as Measured by the Functional Assessment of Cancer Therapy - Lung (FACT-L) Version 4 Test
The FACT-L contains 4 general subscales and a Lung Cancer Subscale (LCS). General subscales include: Physical Well-Being (PWB), Social/ Family Well-Being (SWB), Emotional Well-Being (EWB), and Functional Well-Being (FWB). The LCS assesses symptoms commonly reported by lung cancer patients (e.g., shortness of breath, weight loss, and tightness in the chest). The FACT-L total score ranges from 0 to 136, higher scores represent better QOL. Data were not summarized due to the early termination of the study due to futility.
Time frame: Day 1 (pre-treatment), Day 63 (Cycle 3 Day 1), Day 105 (Cycle 5 Day 1) and end of trial