Non-Small-Cell Lung Adenocarcinoma, Non-small Cell Lung Cancer Stage IIIB, Non-small Cell Lung Cancer Stage IV, Non-small Cell Lung Cancer Metastatic
Conditions
Brief summary
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.
Detailed description
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.
Interventions
DRUGDocetaxel
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.
DRUGGanetespib
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.
Sponsors
Synta Pharmaceuticals Corp.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Advanced Stage IIIB or IV non-small-cell lung cancer (NSCLC) * Eastern Oncology Cooperative Group (ECOG) Performance Status 0 or 1 * Prior therapy defined as 1 prior systemic therapy for advanced disease * Documented disease progression during or following most first line therapy for advanced disease * Adequate hematologic, hepatic, renal function
Exclusion criteria
* Epidermal growth factor receptor (EGFR) mutations * Anaplastic lymphoma kinase (ALK) translocations * Predominantly squamous, adenosquamous or unclear histologic type * Active or untreated central nervous system (CNS) metastases * Active malignancies other than NSCLC within the last 5 years with the exception of adequately treated cone-biopsied in situ carcinoma of the cervix uteri or basal or squamous cell carcinoma of the skin * Serious cardiac illness or medical conditions * Pregnant or lactating women * Uncontrolled intercurrent illness
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival as of 19 October 2015 | up to 36 months | Overall survival (OS) was measured from the date of randomization to the date of death from any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) as of 19 October 2015 | up to 36 months | 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. |
| Overall Survival (OS) In Participants With an Elevated Screening Lactate Dehydrogenase (eLDH) as of 19 October 2015 | up to 36 months | 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. |
| Objective Response Rate (ORR) as of 19 October 2015 | up to 36 months | 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. |
| Disease Control Rate (DCR) as of 19 October 2015 | up to 36 months | 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. |
| Kaplan-Meier Estimate of Duration of Response (DOR) as of 19 October 2015 | up to 36 months | 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. |
| Progression Free Survival (PFS) in Participants With an Elevated Screening Lactate Dehydrogenase (eLDH) as of 19 October 2015 | up to 36 months | 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. |
| Disease Control Rate (DCR) in Participants With an Elevated Screening Lactate Dehydrogenase (eLDH) as of 19 October 2015 | up to 36 months | 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. |
| Kaplan-Meier Estimate for Time to Emergence of New Metastatic Lesion (TNL) as of 19 October 2015 | up to 36 months | 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. |
| Percentage of Participants With Progressive Disease Due to Any New Metastatic Lesion as of 19 October 2015 | up to 36 months | Progressive disease was due to either new metastatic lesions only or new metastatic lesions and target tumor growth. |
| Participants With Treatment-Emergent Adverse Events as of 23 December 2015 | up to 36 months | 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. |
| Patient-Reported Quality of Life as Measured by the European Quality Of Life - Five Dimensions - Three Levels (EQ-5D-3L) Survey | Day 1 (pre-treatment), Day 63 (Cycle 3 Day 1), Day 105 (Cycle 5 Day 1) and end of trial | 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. |
| Patient-Reported Symptom Improvement as Measured by the Functional Assessment of Cancer Therapy - Lung (FACT-L) Version 4 Test | Day 1 (pre-treatment), Day 63 (Cycle 3 Day 1), Day 105 (Cycle 5 Day 1) and end of trial | 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. |
| Objective Response Rate (ORR) in Participants With an Elevated Screening Lactate Dehydrogenase (eLDH) as of 19 October 2015 | up to 36 months | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Exploratory Biomarker Analyses | up to 36 months | Exploratory biomarker analyses was to assess correlation between biomarkers and clinical outcome. However, 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. |
Countries
Austria, Belgium, Bosnia and Herzegovina, Canada, Croatia, Czechia, France, Germany, Hungary, Italy, Netherlands, Poland, Romania, Russia, Serbia, Slovenia, Spain, Ukraine, United Kingdom, United States
Participant flow
Recruitment details
209 sites screened at least one patient and 175 sites randomized at least one patient.
Pre-assignment details
1220 patients with advanced NSCLC of adenocarcinoma histology diagnosed ≥6 months prior to study entry were screened. 696 patients were randomized in a 1:1 ratio to two arms and stratified by: * ECOG (0 versus 1) * Screening total LDH levels (normal vs. elevated) * Geographic region (North America and Western Europe vs. Rest of World)
Participants by arm
| Arm | Count |
|---|---|
| Ganetespib and Docetaxel Ganetespib (150 mg/m\^2) and docetaxel (75 mg/m\^2) were administered as separate 1-hour IV infusions on Day 1 of each 3-week treatment cycle. Administration of ganetespib preceded the administration of docetaxel. Ganetespib was administered again on Day 15 of each cycle. | 347 |
| Docetaxel Docetaxel (75 mg/m\^2) was administered on Day 1 of a 3-week treatment cycle by 1-hour IV infusion. | 349 |
| Total | 696 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 32 | 40 |
| Overall Study | Clinical Progression | 35 | 24 |
| Overall Study | Death | 25 | 22 |
| Overall Study | Lost to Follow-up | 0 | 3 |
| Overall Study | Objective Disease Progression | 152 | 106 |
| Overall Study | Physician Decision | 14 | 10 |
| Overall Study | Sponsor Decision | 61 | 54 |
| Overall Study | Withdrawal by Subject | 27 | 31 |
Baseline characteristics
| Characteristic | Docetaxel | Total | Ganetespib and Docetaxel |
|---|---|---|---|
| Age, Continuous | 60.1 years STANDARD_DEVIATION 8.69 | 60.5 years STANDARD_DEVIATION 8.81 | 60.9 years STANDARD_DEVIATION 8.93 |
| Age, Customized <65 years | 247 participants | 474 participants | 227 participants |
| Age, Customized >=65 years | 102 participants | 222 participants | 120 participants |
| Bone Metastasis No | 249 participants | 481 participants | 232 participants |
| Bone Metastasis Yes | 100 participants | 215 participants | 115 participants |
| Brain Metastasis No | 294 participants | 576 participants | 282 participants |
| Brain Metastasis Yes | 55 participants | 120 participants | 65 participants |
| ECOG at Study Entry 0 = Fully Active | 125 participants | 249 participants | 124 participants |
| ECOG at Study Entry 1 = Restrictive but Ambulatory | 224 participants | 447 participants | 223 participants |
| ECOG at Study Entry 2 = Ambulatory unable to Work | 0 participants | 0 participants | 0 participants |
| ECOG at Study Entry 3 = Limited Self-Care | 0 participants | 0 participants | 0 participants |
| ECOG at Study Entry 4 = Completely Disabled | 0 participants | 0 participants | 0 participants |
| Geographic region North America | 44 participants | 85 participants | 41 participants |
| Geographic region Rest of World | 209 participants | 414 participants | 205 participants |
| Geographic region Western Europe | 96 participants | 197 participants | 101 participants |
| Intra-Thoracic Metastasis only No | 229 participants | 481 participants | 252 participants |
| Intra-Thoracic Metastasis only Yes | 120 participants | 215 participants | 95 participants |
| Lactate Dehydrogenase (LDH) at Study Entry Elevated | 102 participants | 203 participants | 101 participants |
| Lactate Dehydrogenase (LDH) at Study Entry Normal | 247 participants | 493 participants | 246 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 7 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 6 Participants | 4 Participants |
| Race (NIH/OMB) White | 340 Participants | 681 Participants | 341 Participants |
| Sex: Female, Male Female | 135 Participants | 276 Participants | 141 Participants |
| Sex: Female, Male Male | 214 Participants | 420 Participants | 206 Participants |
| Smoking History Ever Smoked | 284 participants | 566 participants | 282 participants |
| Smoking History Never Smoked | 62 participants | 124 participants | 62 participants |
| Smoking History Unknown | 3 participants | 6 participants | 3 participants |
| Stage at Initial Diagnosis I/II | 19 participants | 41 participants | 22 participants |
| Stage at Initial Diagnosis IIIA | 18 participants | 36 participants | 18 participants |
| Stage at Initial Diagnosis IIIB | 52 participants | 104 participants | 52 participants |
| Stage at Initial Diagnosis IV | 258 participants | 512 participants | 254 participants |
| Stage at Initial Diagnosis Unknown | 2 participants | 3 participants | 1 participants |
| Time from Advanced NCSLC Diagnosis to Consent | 11.76 months STANDARD_DEVIATION 7.74 | 11.65 months STANDARD_DEVIATION 6.92 | 11.54 months STANDARD_DEVIATION 5.995 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 293 / 342 | 308 / 338 |
| serious Total, serious adverse events | 107 / 342 | 139 / 338 |
Outcome results
Primary
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
Population: Randomized participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ganetespib and Docetaxel | Overall Survival as of 19 October 2015 | 10.9 months |
| Docetaxel | Overall Survival as of 19 October 2015 | 10.5 months |
Comparison: Primary study hypothesis was tested at a 2-sided, 0.05 significance level using a stratified log-rank test.p-value: 0.329395% CI: [0.899, 1.372]Log Rank
Comparison: Futility analysis for the first Interim Analysis which had a database cutoff of 19 October 2015. For the first interim analysis, if the lower limit of the 2-sided 99.5% confidence interval (CI) for the Hazard Ratio was greater than 0.75, then the study could be stopped for futility, based on Data Monitoring Committee recommendation.~Hazard ratio and 99.5% CI were calculated using the stratified Cox Proportional Hazards model (strata: screening LDH, screening ECOG and geographic region).99.5% CI: [0.821, 1.503]
Secondary
Disease Control Rate (DCR) 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), 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
Population: Randomized participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ganetespib and Docetaxel | Disease Control Rate (DCR) as of 19 October 2015 | >=12 weeks | 46.0 percentage of participants |
| Ganetespib and Docetaxel | Disease Control Rate (DCR) as of 19 October 2015 | >=6 weeks | 64.9 percentage of participants |
| Docetaxel | Disease Control Rate (DCR) as of 19 October 2015 | >=6 weeks | 60.8 percentage of participants |
| Docetaxel | Disease Control Rate (DCR) as of 19 October 2015 | >=12 weeks | 46.9 percentage of participants |
Comparison: \>= 6 weeksp-value: 0.339Fisher Exact
Comparison: \>= 12 weeksp-value: 0.817Fisher Exact
Secondary
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
Population: Randomized participants who had an elevated screening LDH. However, 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.
Secondary
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
Population: Randomized participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ganetespib and Docetaxel | Kaplan-Meier Estimate for Time to Emergence of New Metastatic Lesion (TNL) as of 19 October 2015 | 8.1 months |
| Docetaxel | Kaplan-Meier Estimate for Time to Emergence of New Metastatic Lesion (TNL) as of 19 October 2015 | 8.7 months |
p-value: 0.134395% CI: [0.937, 1.621]Log Rank
Secondary
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
Population: Randomized participants who had a confirmed response
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ganetespib and Docetaxel | Kaplan-Meier Estimate of Duration of Response (DOR) as of 19 October 2015 | 5.8 months |
| Docetaxel | Kaplan-Meier Estimate of Duration of Response (DOR) as of 19 October 2015 | 5.8 months |
p-value: 0.011195% CI: [1.207, 4.551]Log Rank
Secondary
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
Population: Randomized participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ganetespib and Docetaxel | Objective Response Rate (ORR) as of 19 October 2015 | 13.7 percentage of participants |
| Docetaxel | Objective Response Rate (ORR) as of 19 October 2015 | 16.0 percentage of participants |
p-value: 0.448Fisher Exact
Secondary
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
Population: Randomized participants who had an elevated screening LDH. However, 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.
Secondary
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
Population: Randomized participants with elevated LDH at screening
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ganetespib and Docetaxel | Overall Survival (OS) In Participants With an Elevated Screening Lactate Dehydrogenase (eLDH) as of 19 October 2015 | 7.1 months |
| Docetaxel | Overall Survival (OS) In Participants With an Elevated Screening Lactate Dehydrogenase (eLDH) as of 19 October 2015 | 9.0 months |
p-value: 0.250695% CI: [0.865, 1.754]Log Rank
Secondary
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
Population: Safety population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ganetespib and Docetaxel | Participants With Treatment-Emergent Adverse Events as of 23 December 2015 | >=1 SAE leading to study drug discontinuation | 19 participants |
| Ganetespib and Docetaxel | Participants With Treatment-Emergent Adverse Events as of 23 December 2015 | >=1 SAE leading to hospitalization | 109 participants |
| Ganetespib and Docetaxel | Participants With Treatment-Emergent Adverse Events as of 23 December 2015 | >=1 SAE | 139 participants |
| Ganetespib and Docetaxel | Participants With Treatment-Emergent Adverse Events as of 23 December 2015 | >=1 AE | 317 participants |
| Ganetespib and Docetaxel | Participants With Treatment-Emergent Adverse Events as of 23 December 2015 | >=1 AE with CTCAE grade of 3 or 4 | 222 participants |
| Ganetespib and Docetaxel | Participants With Treatment-Emergent Adverse Events as of 23 December 2015 | >=1 AE leading to dose reduction | 61 participants |
| Ganetespib and Docetaxel | Participants With Treatment-Emergent Adverse Events as of 23 December 2015 | >=1 AE leading to delayed dose | 125 participants |
| Ganetespib and Docetaxel | Participants With Treatment-Emergent Adverse Events as of 23 December 2015 | >=1 AE leading to study drug discontinuation | 31 participants |
| Ganetespib and Docetaxel | Participants With Treatment-Emergent Adverse Events as of 23 December 2015 | >=1 SAE with outcome of death | 40 participants |
| Ganetespib and Docetaxel | Participants With Treatment-Emergent Adverse Events as of 23 December 2015 | >=1 AE with first occurrence during Cycle 1-2 | 280 participants |
| Ganetespib and Docetaxel | Participants With Treatment-Emergent Adverse Events as of 23 December 2015 | >=1 AE with first occurrence during Cycle 1-4 | 304 participants |
| Ganetespib and Docetaxel | Participants With Treatment-Emergent Adverse Events as of 23 December 2015 | >=1 AE with first occurrence during Cycle 1-6 | 312 participants |
| Docetaxel | Participants With Treatment-Emergent Adverse Events as of 23 December 2015 | >=1 AE leading to dose reduction | 37 participants |
| Docetaxel | Participants With Treatment-Emergent Adverse Events as of 23 December 2015 | >=1 SAE leading to study drug discontinuation | 15 participants |
| Docetaxel | Participants With Treatment-Emergent Adverse Events as of 23 December 2015 | >=1 AE with first occurrence during Cycle 1-4 | 299 participants |
| Docetaxel | Participants With Treatment-Emergent Adverse Events as of 23 December 2015 | >=1 SAE leading to hospitalization | 87 participants |
| Docetaxel | Participants With Treatment-Emergent Adverse Events as of 23 December 2015 | >=1 AE with first occurrence during Cycle 1-6 | 302 participants |
| Docetaxel | Participants With Treatment-Emergent Adverse Events as of 23 December 2015 | >=1 AE leading to delayed dose | 55 participants |
| Docetaxel | Participants With Treatment-Emergent Adverse Events as of 23 December 2015 | >=1 SAE | 107 participants |
| Docetaxel | Participants With Treatment-Emergent Adverse Events as of 23 December 2015 | >=1 SAE with outcome of death | 30 participants |
| Docetaxel | Participants With Treatment-Emergent Adverse Events as of 23 December 2015 | >=1 AE | 307 participants |
| Docetaxel | Participants With Treatment-Emergent Adverse Events as of 23 December 2015 | >=1 AE leading to study drug discontinuation | 36 participants |
| Docetaxel | Participants With Treatment-Emergent Adverse Events as of 23 December 2015 | >=1 AE with CTCAE grade of 3 or 4 | 184 participants |
| Docetaxel | Participants With Treatment-Emergent Adverse Events as of 23 December 2015 | >=1 AE with first occurrence during Cycle 1-2 | 280 participants |
Secondary
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
Population: Randomized participants. However, 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.
Secondary
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
Population: Randomized participants
Secondary
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
Population: Randomized participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ganetespib and Docetaxel | Percentage of Participants With Progressive Disease Due to Any New Metastatic Lesion as of 19 October 2015 | 34.9 percentage of participants |
| Docetaxel | Percentage of Participants With Progressive Disease Due to Any New Metastatic Lesion as of 19 October 2015 | 30.6 percentage of participants |
p-value: 0.25Fisher Exact
Secondary
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
Population: Randomized participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ganetespib and Docetaxel | Progression-free Survival (PFS) as of 19 October 2015 | 4.2 months |
| Docetaxel | Progression-free Survival (PFS) as of 19 October 2015 | 4.3 months |
p-value: 0.11895% CI: [0.961, 1.403]Log Rank
Secondary
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
Population: Randomized participants who had an elevated screening LDH
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ganetespib and Docetaxel | Progression Free Survival (PFS) in Participants With an Elevated Screening Lactate Dehydrogenase (eLDH) as of 19 October 2015 | 3.0 months |
| Docetaxel | Progression Free Survival (PFS) in Participants With an Elevated Screening Lactate Dehydrogenase (eLDH) as of 19 October 2015 | 2.8 months |
p-value: 0.519195% CI: [0.797, 1.551]Log Rank
Other Pre-specified
Exploratory Biomarker Analyses
Exploratory biomarker analyses was to assess correlation between biomarkers and clinical outcome. However, 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
Population: Randomized