Galaxy 2: A Phase 3 Study of Ganetespib in Combination With Docetaxel Versus Docetaxel Alone in Patients With Advanced NSCLC
Sponsor
Synta Pharmaceuticals Corp. (Industry)
Overall Status
Terminated
CT.gov ID
NCT01798485
Collaborator
(none)
696
268
2
32
2.6
0.1
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 3 |
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.
Study Design
Study Type:
Interventional
Actual Enrollment
:
696 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Randomized, Phase 3 Study of Ganetespib in Combination With Docetaxel Versus Docetaxel Alone in Patients With Advanced Non-Small-Cell Lung Adenocarcinoma
Study Start Date
:
Apr 1, 2013
Actual Primary Completion Date
:
Dec 1, 2015
Actual Study Completion Date
:
Dec 1, 2015
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 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. |
Drug: Docetaxel
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.
Other Names:
Drug: Ganetespib
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.
Other Names:
|
| Active Comparator: Docetaxel Docetaxel (75 mg/m^2) was administered on Day 1 of a 3-week treatment cycle by 1-hour IV infusion. |
Drug: Docetaxel
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.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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.
- 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.
- 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.
Other Outcome Measures
- 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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts 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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Arizona Oncology Associates PC- NAHOA | Flagstaff | Arizona | United States | 86001 |
| 2 | Arizona Oncology Associates, PC- NAHOA | Prescott Valley | Arizona | United States | 86314 |
| 3 | Northern Arizona Hematology & Oncology Associates | Sedona | Arizona | United States | 86336 |
| 4 | Arizona Clinical Research Center, Inc. | Tucson | Arizona | United States | 85715 |
| 5 | Pacific Cancer Medical Center, Inc | Anaheim | California | United States | 92801 |
| 6 | Comprehensive Blood & Cancer Center | Bakersfield | California | United States | 93309 |
| 7 | City of Hope Comprehensive Breast Cancer Center | Duarte | California | United States | 91010 |
| 8 | UC San Diego Moores Cancer Center | La Jolla | California | United States | 92093 |
| 9 | Loma Linda University Cancer Center | Loma Linda | California | United States | 92345 |
| 10 | VA Greater Los Angeles Healthcare System | Los Angeles | California | United States | 90073 |
| 11 | Ronald Reagan UCLA Medical Center | Los Angeles | California | United States | 90095 |
| 12 | St. Joseph Hospital, Center for Cancer Prevention and Treatment | Orange | California | United States | 92868 |
| 13 | Cancer Care Associates Medical Group, Inc. | Redondo Beach | California | United States | 90277 |
| 14 | UC Davis Medical Center - UC Davis Comprehensive Cancer | Sacramento | California | United States | 95817 |
| 15 | Santa Barbara Hematology Oncology Medical Group, Inc. | Santa Barbara | California | United States | 93105-4230 |
| 16 | City of Hope- South Pasadena | South Pasadena | California | United States | 91030 |
| 17 | Rocky Mountain Cancer Center | Denver | Colorado | United States | 80218 |
| 18 | Eastern Connecticut Hematology Associates | Norwich | Connecticut | United States | 06360 |
| 19 | Medical Oncology Hematology Consultants, PA | Newark | Delaware | United States | 19713 |
| 20 | Lynn Cancer Institute Center for Hematology Oncology | Boca Raton | Florida | United States | 33486 |
| 21 | Halifax Health - Medical Center | Daytona Beach | Florida | United States | 32114 |
| 22 | University of Miami Health System Sylvester at Deerfield Beach | Deerfield Beach | Florida | United States | 33442-7753 |
| 23 | Memorial Regional Hospital | Hollywood | Florida | United States | 33021 |
| 24 | Baptist Health Medical Group Oncology, LLC | Miami | Florida | United States | 33176 |
| 25 | University of South Florida - H. Lee Moffitt | Tampa | Florida | United States | 33612 |
| 26 | Palm Beach Cancer Institute | West Palm Beach | Florida | United States | 33401 |
| 27 | Emory University - Winship Cancer Institute | Atlanta | Georgia | United States | 30322 |
| 28 | Northwest Georgia Oncology Centers, PC | Marietta | Georgia | United States | 30060 |
| 29 | University Of Chicago Medical Center | Chicago | Illinois | United States | 60637 |
| 30 | Cancer Care Specialists of Central Illinois, S.C. | Decatur | Illinois | United States | 62526 |
| 31 | Saint Anthony Medical Center | Rockford | Illinois | United States | 61108 |
| 32 | Fort Wayne Medical Oncology and Hematology Inc | Fort Wayne | Indiana | United States | 46804 |
| 33 | AAMC Oncology and Hematology | Annapolis | Maryland | United States | 21401 |
| 34 | The Center for Cancer and Blood Disorders (CCBD) - Bethesda | Bethesda | Maryland | United States | 20817 |
| 35 | The John R Marsh Cancer Center | Hagerstown | Maryland | United States | 21742 |
| 36 | Dana Farber Cancer Institute | Boston | Massachusetts | United States | 02114 |
| 37 | Dana Farber Cancer Institute | Boston | Massachusetts | United States | 02215 |
| 38 | Henry Ford Hospital | Detroit | Michigan | United States | 48202 |
| 39 | Sparrow Regional Cancer Center | Lansing | Michigan | United States | 48909 |
| 40 | St. Luke's Hospital Duluth | Duluth | Minnesota | United States | 55805 |
| 41 | Frauenshuh Cancer Center | Saint Louis Park | Minnesota | United States | 55426 |
| 42 | St. Louis Cancer Care, LLP - North County | Bridgeton | Missouri | United States | 63044 |
| 43 | Renown Regional Medical Center | Reno | Nevada | United States | 89502 |
| 44 | Hackensack University Medical Center - John Theurer Cancer Center | Hackensack | New Jersey | United States | 07601 |
| 45 | New Mexico Cancer Center | Albuquerque | New Mexico | United States | 87109 |
| 46 | North Shore Hematology Oncology Associates | East Setauket | New York | United States | 11733 |
| 47 | Clinical Research Alliance | Lake Success | New York | United States | 11042 |
| 48 | University Of North Carolina At Chapel Hill | Chapel Hill | North Carolina | United States | 27599 |
| 49 | Novant Health Presbyterian Medical Center | Charlotte | North Carolina | United States | 28204 |
| 50 | New Hanover Regional Medical Center - Zimmer Cancer Center | Wilmington | North Carolina | United States | 28401 |
| 51 | Novant Health Oncology Specialists | Winston-Salem | North Carolina | United States | 27103 |
| 52 | Tulsa Cancer Institute, PLLC | Tulsa | Oklahoma | United States | 74146 |
| 53 | Kaiser Permanente Northwest | Portland | Oregon | United States | 97227 |
| 54 | University of Pittsburgh Medical Center | Pittsburgh | Pennsylvania | United States | 15232 |
| 55 | Guthrie Medical Group, PC | Sayre | Pennsylvania | United States | 18840 |
| 56 | Rapid City Regional Hospital | Rapid City | South Dakota | United States | 57701 |
| 57 | Prairie Lakes Healthcare System | Watertown | South Dakota | United States | 57201 |
| 58 | Erlanger Institute for Clinical Research | Chattanooga | Tennessee | United States | 37403 |
| 59 | Associates In Oncology and Hematology | Chattanooga | Tennessee | United States | 37421 |
| 60 | Thompson Cancer Survival Center | Knoxville | Tennessee | United States | 37916 |
| 61 | Texas Oncology-Arlington North | Arlington | Texas | United States | 76012 |
| 62 | Texas Oncology - Arlington South | Arlington | Texas | United States | 76014 |
| 63 | Texas Oncology, P.A. | Beaumont | Texas | United States | 77702 |
| 64 | Texas Oncology, PA | Dallas | Texas | United States | 75246 |
| 65 | Simmons Comprehensive Cancer Center | Dallas | Texas | United States | 75390 |
| 66 | Houston Methodist Hospital Research Institute | Houston | Texas | United States | 77030 |
| 67 | Millennium Oncology | Houston | Texas | United States | 77090 |
| 68 | Joe Arrington Cancer Research and Treatment Center | Lubbock | Texas | United States | 79410 |
| 69 | Cancer Care Centers Of South Texas | San Antonio | Texas | United States | 78212 |
| 70 | Cancer Care Centers Of South Texas | San Antonio | Texas | United States | 78217 |
| 71 | Cancer Care Centers of South Texas | San Antonio | Texas | United States | 78258 |
| 72 | Texas Oncology - Sherman | Sherman | Texas | United States | 75090 |
| 73 | Providence Regional Medical Center Everett | Everett | Washington | United States | 98201 |
| 74 | Cancer Care Northwest | Spokane Valley | Washington | United States | 99216 |
| 75 | Northwest Medical Specialties, PLLC | Tacoma | Washington | United States | 98405 |
| 76 | Mary Babb Cancer Center | Morgantown | West Virginia | United States | 26506 |
| 77 | Green Bay Oncology, Ltd. - St. Mary's Site | Green Bay | Wisconsin | United States | 54303-3216 |
| 78 | Green Bay Oncology | Green Bay | Wisconsin | United States | 54307 |
| 79 | Landesklinikum Krems | Krems | Niederösterreich | Austria | 3500 |
| 80 | Krankenhaus Der Barmherzigen Schwestern | Linz | Oberösterreich | Austria | 4010 |
| 81 | Klinikum Wels-Grieskirchen | Wels | Oberösterreich | Austria | A-4600 |
| 82 | Bezirkskrankenhaus Kufstein [Onkologie] | Kufstein | Tirol | Austria | A-6330 |
| 83 | Allgemeines Krankenhaus Linz | Linz | Austria | 4021 | |
| 84 | Elisabeth Linz Hospital | Linz | Austria | 4021 | |
| 85 | Otto Wagner Spital | Wien | Austria | 1140 | |
| 86 | Sozialmedizinisches Zentrum Baumgartner Höhe | Wien | Austria | 1145 | |
| 87 | AZ Sint-Maarten - Campus Leopoldstraat | Mechelen | Antwerpen | Belgium | 2800 |
| 88 | Clinique Saint-Pierre Ottignies | Ottignies | Brabant Wallon | Belgium | 1340 |
| 89 | Grand Hôpital de Charleroi - Site Notre-Dame | Charleroi | Hainaut | Belgium | 6000 |
| 90 | INDC Entité Jolimontoise - Polyclinique de Jolimont | Haine St. Paul | Hainaut | Belgium | 1700 |
| 91 | CHU Dinant Godinne UCL Namur | Yvoir | Namur | Belgium | 5533 |
| 92 | Algemeen Stedelijk Ziekenhuis - Campus Aalst | Roeselaere | West-Vlaanderen | Belgium | 8800 |
| 93 | Cliniques Universitaire Saint-Luc | Bruxelles | Belgium | 1200 | |
| 94 | CHR de la Citadelle - Site Citadelle | Liège | Belgium | 4000 | |
| 95 | Clinical Centre Banja Luka | Banja Luka | Republika Srpska | Bosnia and Herzegovina | 78000 |
| 96 | University Clinical Center Tuzla | Tuzla | Tuzlanski kanton | Bosnia and Herzegovina | 75000 |
| 97 | Clinical Hospital Mostar | Mostar | Bosnia and Herzegovina | 88108 | |
| 98 | Clinical Center University of Sarajevo, Clinic of Oncology | Sarajevo | Bosnia and Herzegovina | 71000 | |
| 99 | University Clinical Centre Sarajevo | Sarajevo | Bosnia and Herzegovina | 71000 | |
| 100 | University Clinical Center Tuzla | Tuzla | Bosnia and Herzegovina | 75000 | |
| 101 | Kantonalna bolnica Zenica | Zenica | Bosnia and Herzegovina | 72000 | |
| 102 | Princess Margaret Hospital | Toronto | Ontario | Canada | MG5 2M9 |
| 103 | Mc Gill University-MUHC | Montreal | Quebec | Canada | H2W 1S6 |
| 104 | University Hospital Center Zagreb | Zagreb | Grad Zagreb | Croatia | 10 000 |
| 105 | Opca bolnica Pula | Pula | Istarska županija | Croatia | 52000 |
| 106 | Fakultni nemocnice Olomouc | Olomouc | Czech Republic | 775 20 | |
| 107 | Fakultni nemocnice Ostrava | Ostrava - Poruba | Czech Republic | 708 52 | |
| 108 | Vseobecna fakultni nemocnice v Praze | Prague | Czech Republic | 128 08 | |
| 109 | Nemocnice Na Bulovce | Prague | Czech Republic | 180 81 | |
| 110 | CHI des Alpes du Sud | Gap | Hautes-Alpes | France | 5000 |
| 111 | Centre D'Oncologie Du Pays Basque | Bayonne | Pyrénées-Atlantiques | France | 64100 |
| 112 | Centre Hosptalier De Villefranche-Sur-Saone | Villefranche Sur Saone | Rhône | France | 69655 |
| 113 | Chi creteil | Creteil | Val-de-Marne | France | 94010 |
| 114 | Chu De Grenoble - Hopital Michallon | Grenoble | France | 38700 | |
| 115 | Centre Léon Bérard | Lyon | France | 69373 | |
| 116 | Groupe Hospitalier Cochin | Paris | France | 75679 | |
| 117 | Centre Hospitalier Universitaire de Rennes - Hopital d | Rennes | France | 35033 | |
| 118 | Hôpital Charles Nicolle | Rouen | France | 76000 | |
| 119 | CHRU de Strasbourg | Strasbourg | France | 67091 | |
| 120 | Universitätsklinikum Freiburg | Freiburg | Baden-Württemberg | Germany | 79106 |
| 121 | Universiaetsklinikum Ulm | Ulm | Baden-Württemberg | Germany | 89081 |
| 122 | Schwarzwald-Baar-Klinikum | Villingen-Schwenningen | Baden-Württemberg | Germany | 78052 |
| 123 | Asklepios Fachklinik München-Gauting | Gauting | Bayern | Germany | 82131 |
| 124 | Klinikum Bogenhausen | Muenchen | Bayern | Germany | 81925 |
| 125 | Gesundheitszentrum Wetterau | Bad Nauheim | Hessen | Germany | 61231 |
| 126 | Johann Wolfgang Goethe University Clinic Frankfurt | Frankfurt | Hessen | Germany | 60590 |
| 127 | Johann Wolfgang Goethe University Clinic Frankfurt | Frankfurt | Hessen | Germany | D-60590 |
| 128 | Klinikum Kassel | Kassel | Hessen | Germany | 34125 |
| 129 | Kliniken der Stadt Köln gGmbH | Köln | Nordrhein-Westfalen | Germany | 51109 |
| 130 | Universitaetsklinikum des Saarlandes | Homburg | Saarland | Germany | 66421 |
| 131 | Universitätsklinikum Leipzig [Pneumologie] | Leipzig | Sachsen | Germany | 04103 |
| 132 | Pneumologisches Forschungsinstitut an der Lungenclinic Gross | Großhansdorf | Schleswig-Holstein | Germany | 22927 |
| 133 | MVZ Äerzteforum Seestraße | Berlin | Germany | 13347 | |
| 134 | Ev. Krankenhaus Bielefeld | Bielefeld | Germany | 33611 | |
| 135 | Klinikum Frankfurt An Der Oder | Frankfurt/Oder | Germany | 15236 | |
| 136 | Practice Laack | Hamburg | Germany | 20251 | |
| 137 | Unikl. Schleswig-Holstein - Lübeck | Lübeck | Germany | 23538 | |
| 138 | J. Gutenberg Uni.Mainz | Mainz | Germany | 55101 | |
| 139 | Medizinische Fakultät Mannheim Uni Heidelberg | Mannheim | Germany | 68167 | |
| 140 | Gemeinschaftspraxis fuer Haematologie und Onkologie | Muenster | Germany | 48149 | |
| 141 | Klinikum Offenbach GmbH | Offenbach | Germany | 63069 | |
| 142 | Csongrád Megyei Önkormányzat Mellkasi Betegségek Szakkó | Deszk | Csongrád | Hungary | 6772 |
| 143 | Fejér Megyei Szent György Egyetemi Oktató Kórház | Székesfehérvár | Fejér | Hungary | 8000 |
| 144 | Országos Korányi TBC és Pulmonológiai Intézet | Budapest | Pest | Hungary | 1145 |
| 145 | Semmelweis Egyetem | Budapest | Hungary | 1125 | |
| 146 | Országos Korányi TBC és Pulmonológiai Intézet | Budapest | Hungary | 1529 | |
| 147 | Békés Megyei Pándy Kálmán Kórház | Gyula | Hungary | 5703 | |
| 148 | CRU Hungary Kft. | Miskolc | Hungary | 3529 | |
| 149 | Irccs Irst | Meldola | Forli | Italy | 47014 |
| 150 | Presidio Ospedaliero Centrale Belcolle, AUSL Viterbo | Viterbo | Lazio | Italy | 01100 |
| 151 | Azienda Ospedaliera San Gerardo | Monza | Lombardia | Italy | 20900 |
| 152 | CRO, IRCCS, Istituto Nazionale Tumori | Aviano | Pordenone | Italy | 33081 |
| 153 | Azienda Policlinico Umberto I | Rome | Roma | Italy | 00161 |
| 154 | Policlinico S.Orsola Malpighi, AOU di Bologna | Bologna | Italy | 40138 | |
| 155 | AOU S.Martino, IRCCS, IST-Istituto Nazionale Ricerca Sul Can | Genova | Italy | 16132 | |
| 156 | Istituto Europeo di Oncologia, Istituto di Ricovero e Cura a | Milano | Italy | 20141 | |
| 157 | Iov-Irccs | Padova | Italy | 35128 | |
| 158 | Ospedale S.Maria della Misericordia, AO di Perugia, Universi | Perugia | Italy | 06156 | |
| 159 | Ospedale Guglielmo da Saliceto, AUSL Piacenza | Piacenza | Italy | 29100 | |
| 160 | Istituti Fisioterapici Ospitalieri Regina Elena | Roma | Italy | 00144 | |
| 161 | Borgo Roma, Policlinico G.Rossi, AOU Integrata Verona | Verona | Italy | 37134 | |
| 162 | Ziekenhuis Assen | Assen | Drenthe | Netherlands | 9401 RK |
| 163 | Ziekenhuis St Jansdal | Harderwijk | Gelderland | Netherlands | 3844 DG |
| 164 | Gelre Ziekenhuis Zutphen | Zutphen | Gelderland | Netherlands | 7207 AE |
| 165 | academisch ziekenhuis Maastricht | Maastricht | Limburg | Netherlands | 6229 HX |
| 166 | Isala Klinieken Zwolle | Zwolle | Overijssel | Netherlands | 8025 AB |
| 167 | Sint Antoniusziekenhuis, location Utrecht | Utrecht | Netherlands | 3543 AZ | |
| 168 | Wojewodzki Szpital Specjalistyczny im. M.Kopernika | Lodz | Lodzkie | Poland | 93-513 |
| 169 | Medica Pro Familia Sp. z o.o. S.K.A. | Krakow | Malopolskie | Poland | 31-002 |
| 170 | Mazowieckie Centrum Leczenia Chorob Pluc i Gruzlicy | Otwock | Mazowieckie | Poland | 05-400 |
| 171 | Centrum Onkologii - Instytut im. Marii Sklodowskiej - Curie | Warszawa | Mazowieckie | Poland | 02-781 |
| 172 | Uniwersytecki Szpital Kliniczny w Bialymstoku | Bialystok | Podlaskie | Poland | 15-540 |
| 173 | Szpital Wojewodzki w Lomzy im. Kardynala S. Wyszynskiego | Lomza | Podlaskie | Poland | 18-400 |
| 174 | Szpital Wojewodzki Zespolony | Elblag | Warminsko-mazurskie | Poland | 82-300 |
| 175 | NZOZ Med Polonia | Poznan | Wielkopolskie | Poland | 60-693 |
| 176 | Wielkopolskie Centrum Pulmonologii i Torakochirurgii | Poznan | Wielkopolskie | Poland | 60569 |
| 177 | Samodzielny Publiczny Zespol Gruzlicy i Chorob Pluc | Olsztyn | Poland | 10-357 | |
| 178 | Szpital Chorob Pluc im. Sw. Jozefa w Pilchowicach | Pilchowice | Poland | 44145 | |
| 179 | Szpital Specjalistyczny | Prabuty | Poland | 82-550 | |
| 180 | Institutul Oncologic "Prof. Dr. Alex. Trestioreanu" | Bucharest | Romania | 022328 | |
| 181 | Spitalul Universitar de Urgenta Bucuresti | Bucharest | Romania | 050098 | |
| 182 | Spitalul Clinic Coltea | Bucuresti | Romania | 030171 | |
| 183 | Institutul Oncologic "Prof.Dr.I.Chiricuta" Cluj Napoca | Cluj Napoca | Romania | 400015 | |
| 184 | Medisprof | Cluj Napoca | Romania | 400058 | |
| 185 | Institutul Oncologic "Prof.Dr.I.Chiricuta" Cluj Napoca | Cluj-Napoca | Romania | 400015 | |
| 186 | Centrul de Oncologie Sf. Nectarie | Craiova | Romania | 200385 | |
| 187 | Institutul Regional de Oncologie Iasi | Iasi | Romania | 700483 | |
| 188 | Oncomed | Timisoara | Romania | 300239 | |
| 189 | Synta Pharmaceuticals Investigational Site | Chelyabinsk | Russian Federation | 454087 | |
| 190 | Synta Pharmaceuticals Investigational Site | Ekaterinburg | Russian Federation | 620036 | |
| 191 | Synta Pharmaceuticals Investigational Site | Ivanovo | Russian Federation | 153040 | |
| 192 | Synta Pharmaceuticals Investigational Site | Izhevsk | Russian Federation | 426067 | |
| 193 | Synta Pharmaceuticals Investigational Site | Kemerovo | Russian Federation | 650036 | |
| 194 | Synta Pharmaceuticals Investigational Site | Krasnoyarsk | Russian Federation | 660133 | |
| 195 | Synta Pharmaceuticals Investigational Site | Kursk | Russian Federation | 305035 | |
| 196 | Synta Pharmaceuticals Investigational Site | Lipetsk | Russian Federation | 398005 | |
| 197 | Synta Pharmaceuticals Investigational Site | Moscow | Russian Federation | 115478 | |
| 198 | Synta Pharmaceuticals Investigational Site | Nizhny Novgorod | Russian Federation | 603081 | |
| 199 | Synta Pharmaceuticals Investigational Site | Novosibirsk | Russian Federation | 630047 | |
| 200 | Synta Pharmaceuticals Investigational Site | Omsk | Russian Federation | 644013 | |
| 201 | Synta Pharmaceuticals Investigational Site | Orel | Russian Federation | 302020 | |
| 202 | Synta Pharmaceuticals Investigational Site | Rostov-on-Don | Russian Federation | 344037 | |
| 203 | Synta Pharmaceuticals Investigational Site | Samara | Russian Federation | 443031 | |
| 204 | Synta Pharmaceuticals Investigational Site | Saransk | Russian Federation | 430032 | |
| 205 | Synta Pharmaceuticals Investigational Site | Sochi | Russian Federation | 354057 | |
| 206 | Synta Pharmaceuticals Investigational Site | St. Petersburg | Russian Federation | 194017 | |
| 207 | Synta Pharmaceuticals Investigational Site | St. Petersburg | Russian Federation | 197758 | |
| 208 | Synta Pharmaceuticals Investigational Site | St. Petersburg | Russian Federation | 198255 | |
| 209 | Synta Pharmaceuticals Investigational Site | Stavropol | Russian Federation | 355047 | |
| 210 | Synta Pharmaceuticals Investigational Site | Ufa | Russian Federation | 450000 | |
| 211 | Synta Pharmaceuticals Investigational Site | Ufa | Russian Federation | 450054 | |
| 212 | Clinical Centre of Serbia | Beograd | Belgrade | Serbia | 11000 |
| 213 | Clinical Centre Nis | Nis | Nišavski okrug | Serbia | 18000 |
| 214 | Institute for Oncology and Radiology of Serbia | Belgrade | Serbia | 11000 | |
| 215 | Institute for pulmonary diseases of Vojvodine | Sremska Kamenica | Serbia | 21204 | |
| 216 | Clinical Center Kragujevac | Kragujevac | Šumadijski okrug | Serbia | 34 000 |
| 217 | Univerzitetna klinika za pljucne bolesti in alergijo Golnik | Golnik | Slovenia | 4204 | |
| 218 | Onkoloski institut Ljubljana | Ljubljana | Slovenia | 1000 | |
| 219 | Xerencia de Xestión Integrada A Coruña Hospital Teresa Herrera | La Coruña | A Coruña | Spain | 15006 |
| 220 | Synta Pharmaceuticals Investigational Site | Málaga | Andalucía | Spain | 29010 |
| 221 | Synta Pharmaceuticals Investigational Site | Oviedo | Asturias | Spain | 33006 |
| 222 | H. Son Llàtzer | Palma de Mallorca | Baleares | Spain | 07198 |
| 223 | Hospital de Mataró, Consorci Sanitari del Maresme | Mataró | Barcelona | Spain | 08304 |
| 224 | Synta Pharmaceuticals Investigational Site | Santander | Cantabria | Spain | 39008 |
| 225 | Onkologikoa | San Sebastian | Guipuzcoa | Spain | 20014 |
| 226 | Hospital Universitari Germans Trias i Pujol | Badalona | Spain | 08916 | |
| 227 | H.U. Vall d'Hebrón | Barcelona | Spain | 08035 | |
| 228 | Synta Pharmaceuticals Investigational Site | Barcelona | Spain | 08036 | |
| 229 | H.U. Reina Sofía | Córdoba | Spain | 14004 | |
| 230 | Synta Pharmaceuticals Investigational Site | Girona | Spain | 17007 | |
| 231 | Synta Pharmaceuticals Investigational Site | Madrid | Spain | 28033 | |
| 232 | Hospital Universitario Ramón y Cajal | Madrid | Spain | 28034 | |
| 233 | Synta Pharmaceuticals Investigational Site | Madrid | Spain | 28034 | |
| 234 | F. Jiménez Diaz | Madrid | Spain | 28040 | |
| 235 | Synta Pharmaceuticals Investigational Site | Madrid | Spain | 28041 | |
| 236 | Hospital Madrid Norte Sanchinarro | Madrid | Spain | 28050 | |
| 237 | Synta Pharmaceuticals Investigational Site | Madrid | Spain | 28223 | |
| 238 | Hospital Universitario Virgen del Rocío | Sevilla | Spain | 41013 | |
| 239 | Hospital Universitari i Politecnic La Fe | Valencia | Spain | 460026 | |
| 240 | Synta Pharmaceuticals Investigational Site | Cherkasy | Ukraine | 18009 | |
| 241 | Synta Pharmaceuticals Investigational Site | Chernivtsi | Ukraine | 58013 | |
| 242 | Synta Pharmaceuticals Investigational Site | Dnepropetrovsk | Ukraine | 49102 | |
| 243 | Synta Pharmaceuticals Investigational Site | Donetsk | Ukraine | 83087 | |
| 244 | Synta Pharmaceuticals Investigational Site | Donetsk | Ukraine | 83092 | |
| 245 | Synta Pharmaceuticals Investigational Site | Ivano-Frankivsk | Ukraine | 76000 | |
| 246 | Synta Pharmaceuticals Investigative Site | Kharkiv | Ukraine | 61070 | |
| 247 | Synta Pharmaceuticals Investigational Site | Khmelnytskyi | Ukraine | 29009 | |
| 248 | Synta Pharmaceuticals Investigational Site | Kirovohrad | Ukraine | 25011 | |
| 249 | Synta Pharmaceuticals Investigational Site | Kryvyi Rih | Ukraine | 50048 | |
| 250 | Synta Pharmaceuticals Investigational Site | Kyiv | Ukraine | 03115 | |
| 251 | Synta Pharmaceuticals Investigational Site | Makiivka | Ukraine | 86120 | |
| 252 | Synta Pharmaceuticals Investigational Site | Poltava | Ukraine | 36011 | |
| 253 | Synta Pharmaceuticals Investigational Site | Simferopol | Ukraine | 95023 | |
| 254 | Synta Pharmaceuticals Investigational Site | Sumy | Ukraine | 40022 | |
| 255 | Synta Pharmaceuticals Investigational Site | Uzhhorod | Ukraine | 88014 | |
| 256 | Synta Pharmaceuticals Investigational Site | Vinnytsia | Ukraine | 21021 | |
| 257 | Synta Pharmaceuticals Investigational Site | Truro | Cornwall | United Kingdom | TR1 3LJ |
| 258 | Synta Pharmaceuticals Investigational Site | Shrewsbury | Shropshire | United Kingdom | SY3 8XQ |
| 259 | Synta Pharmaceuticals Investigational Site | Sutton | Surrey | United Kingdom | SM2 5PT |
| 260 | Synta Pharmaceuticals Investigational Site | Swindon | Wiltshire | United Kingdom | SN3 6BB |
| 261 | Synta Pharmaceuticals Investigational Site | Cardiff | United Kingdom | CF14 2TL | |
| 262 | Synta Pharmaceuticals Investigational Site | Edinburgh | United Kingdom | EH4 2XU | |
| 263 | Synta Pharmaceuticals Investigational Site | Leicester | United Kingdom | LEI 5WW | |
| 264 | Synta Pharmaceuticals Investigational Site | London | United Kingdom | SE1 9RT | |
| 265 | Synta Pharmaceuticals Investigational Site | London | United Kingdom | SW3 6JJ | |
| 266 | Synta Pharmaceuticals Investigational Site | London | United Kingdom | W6 8RF | |
| 267 | Synta Pharmaceuticals Investigational Site | Nottingham | United Kingdom | NG5 1PB | |
| 268 | Synta Pharmaceuticals Investigational Site | Southampton | United Kingdom | SO16 6YD |
Sponsors and Collaborators
- Synta Pharmaceuticals Corp.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Synta Pharmaceuticals Corp.
ClinicalTrials.gov Identifier:
NCT01798485
Other Study ID Numbers:
- 9090-14
- 2012-004349-34
First Posted:
Feb 25, 2013
Last Update Posted:
Jul 1, 2016
Last Verified:
May 1, 2016
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | 209 sites screened at least one patient and 175 sites randomized at least one patient. |
|---|---|
| Pre-assignment Detail | 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) |
| Arm/Group Title | Ganetespib and Docetaxel | Docetaxel |
|---|---|---|
| Arm/Group Description | 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. | Docetaxel (75 mg/m^2) was administered on Day 1 of a 3-week treatment cycle by 1-hour IV infusion. |
| Period Title: Overall Study | ||
| STARTED | 347 | 349 |
| Safety Population as of 23 Dec 2015 | 338 | 342 |
| Randomized as of 19 October 2015 | 335 | 337 |
| COMPLETED | 1 | 59 |
| NOT COMPLETED | 346 | 290 |
Baseline Characteristics
| Arm/Group Title | Ganetespib and Docetaxel | Docetaxel | Total |
|---|---|---|---|
| Arm/Group Description | 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. | Docetaxel (75 mg/m^2) was administered on Day 1 of a 3-week treatment cycle by 1-hour IV infusion. | Total of all reporting groups |
| Overall Participants | 347 | 349 | 696 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
60.9
(8.93)
|
60.1
(8.69)
|
60.5
(8.81)
|
| Age, Customized (participants) [Number] | |||
| <65 years |
227
65.4%
|
247
70.8%
|
474
68.1%
|
| >=65 years |
120
34.6%
|
102
29.2%
|
222
31.9%
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
141
40.6%
|
135
38.7%
|
276
39.7%
|
| Male |
206
59.4%
|
214
61.3%
|
420
60.3%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
| Asian |
1
0.3%
|
1
0.3%
|
2
0.3%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
1
0.3%
|
6
1.7%
|
7
1%
|
| White |
341
98.3%
|
340
97.4%
|
681
97.8%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
4
1.2%
|
2
0.6%
|
6
0.9%
|
| Geographic region (participants) [Number] | |||
| North America |
41
11.8%
|
44
12.6%
|
85
12.2%
|
| Western Europe |
101
29.1%
|
96
27.5%
|
197
28.3%
|
| Rest of World |
205
59.1%
|
209
59.9%
|
414
59.5%
|
| Smoking History (participants) [Number] | |||
| Never Smoked |
62
17.9%
|
62
17.8%
|
124
17.8%
|
| Ever Smoked |
282
81.3%
|
284
81.4%
|
566
81.3%
|
| Unknown |
3
0.9%
|
3
0.9%
|
6
0.9%
|
| Time from Advanced NCSLC Diagnosis to Consent (months) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [months] |
11.54
(5.995)
|
11.76
(7.740)
|
11.65
(6.920)
|
| Stage at Initial Diagnosis (participants) [Number] | |||
| I/II |
22
6.3%
|
19
5.4%
|
41
5.9%
|
| IIIA |
18
5.2%
|
18
5.2%
|
36
5.2%
|
| IIIB |
52
15%
|
52
14.9%
|
104
14.9%
|
| IV |
254
73.2%
|
258
73.9%
|
512
73.6%
|
| Unknown |
1
0.3%
|
2
0.6%
|
3
0.4%
|
| ECOG at Study Entry (participants) [Number] | |||
| 0 = Fully Active |
124
35.7%
|
125
35.8%
|
249
35.8%
|
| 1 = Restrictive but Ambulatory |
223
64.3%
|
224
64.2%
|
447
64.2%
|
| 2 = Ambulatory unable to Work |
0
0%
|
0
0%
|
0
0%
|
| 3 = Limited Self-Care |
0
0%
|
0
0%
|
0
0%
|
| 4 = Completely Disabled |
0
0%
|
0
0%
|
0
0%
|
| Lactate Dehydrogenase (LDH) at Study Entry (participants) [Number] | |||
| Normal |
246
70.9%
|
247
70.8%
|
493
70.8%
|
| Elevated |
101
29.1%
|
102
29.2%
|
203
29.2%
|
| Brain Metastasis (participants) [Number] | |||
| Yes |
65
18.7%
|
55
15.8%
|
120
17.2%
|
| No |
282
81.3%
|
294
84.2%
|
576
82.8%
|
| Bone Metastasis (participants) [Number] | |||
| Yes |
115
33.1%
|
100
28.7%
|
215
30.9%
|
| No |
232
66.9%
|
249
71.3%
|
481
69.1%
|
| Intra-Thoracic Metastasis only (participants) [Number] | |||
| Yes |
95
27.4%
|
120
34.4%
|
215
30.9%
|
| No |
252
72.6%
|
229
65.6%
|
481
69.1%
|
Outcome Measures
| Title | Overall Survival as of 19 October 2015 |
|---|---|
| Description | Overall survival (OS) was measured from the date of randomization to the date of death from any cause. |
| Time Frame | up to 36 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomized participants |
| Arm/Group Title | Ganetespib and Docetaxel | Docetaxel |
|---|---|---|
| Arm/Group Description | 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. | Docetaxel (75 mg/m^2) was administered on Day 1 of a 3-week treatment cycle by 1-hour IV infusion. |
| Measure Participants | 335 | 337 |
| Median (95% Confidence Interval) [months] |
10.9
|
10.5
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Ganetespib and Docetaxel, Docetaxel |
|---|---|---|
| Comments | Primary study hypothesis was tested at a 2-sided, 0.05 significance level using a stratified log-rank test. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3293 |
| Comments | ||
| Method | Log Rank | |
| Comments | P-value was from stratified log-rank test (strata: screening LDH, screening ECOG and geographic region). | |
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.111 | |
| Confidence Interval |
(2-Sided) 95% 0.899 to 1.372 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Ganetespib and Docetaxel, Docetaxel |
|---|---|---|
| Comments | 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). | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.111 | |
| Confidence Interval |
(2-Sided) 99.5% 0.821 to 1.503 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Progression-free Survival (PFS) as of 19 October 2015 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomized participants |
| Arm/Group Title | Ganetespib and Docetaxel | Docetaxel |
|---|---|---|
| Arm/Group Description | 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. | Docetaxel (75 mg/m^2) was administered on Day 1 of a 3-week treatment cycle by 1-hour IV infusion. |
| Measure Participants | 335 | 337 |
| Median (95% Confidence Interval) [months] |
4.2
|
4.3
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Ganetespib and Docetaxel, Docetaxel |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1180 |
| Comments | Significance level of 0.05. | |
| Method | Log Rank | |
| Comments | Stratified log-rank test with stratification variables, ECOG, screening total LDH levels, and geographic region, used to compare the treatment groups. | |
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.161 | |
| Confidence Interval |
(2-Sided) 95% 0.961 to 1.403 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Overall Survival (OS) In Participants With an Elevated Screening Lactate Dehydrogenase (eLDH) as of 19 October 2015 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomized participants with elevated LDH at screening |
| Arm/Group Title | Ganetespib and Docetaxel | Docetaxel |
|---|---|---|
| Arm/Group Description | 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. | Docetaxel (75 mg/m^2) was administered on Day 1 of a 3-week treatment cycle by 1-hour IV infusion. |
| Measure Participants | 99 | 98 |
| Median (95% Confidence Interval) [months] |
7.1
|
9.0
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Ganetespib and Docetaxel, Docetaxel |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2506 |
| Comments | Significance level of 0.05. | |
| Method | Log Rank | |
| Comments | P-value was from stratified log-rank test (strata: screening ECOG and geographic region). | |
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.232 | |
| Confidence Interval |
(2-Sided) 95% 0.865 to 1.754 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Objective Response Rate (ORR) as of 19 October 2015 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomized participants |
| Arm/Group Title | Ganetespib and Docetaxel | Docetaxel |
|---|---|---|
| Arm/Group Description | 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. | Docetaxel (75 mg/m^2) was administered on Day 1 of a 3-week treatment cycle by 1-hour IV infusion. |
| Measure Participants | 335 | 337 |
| Number (95% Confidence Interval) [percentage of participants] |
13.7
3.9%
|
16.0
4.6%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Ganetespib and Docetaxel, Docetaxel |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.448 |
| Comments | Significance level of 0.05. | |
| Method | Fisher Exact | |
| Comments | ||
| Title | Disease Control Rate (DCR) as of 19 October 2015 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomized participants |
| Arm/Group Title | Ganetespib and Docetaxel | Docetaxel |
|---|---|---|
| Arm/Group Description | 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. | Docetaxel (75 mg/m^2) was administered on Day 1 of a 3-week treatment cycle by 1-hour IV infusion. |
| Measure Participants | 335 | 337 |
| >=6 weeks |
64.9
18.7%
|
60.8
17.4%
|
| >=12 weeks |
46.0
13.3%
|
46.9
13.4%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Ganetespib and Docetaxel, Docetaxel |
|---|---|---|
| Comments | >= 6 weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.339 |
| Comments | Significance level of 0.05. | |
| Method | Fisher Exact | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Ganetespib and Docetaxel, Docetaxel |
|---|---|---|
| Comments | >= 12 weeks | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.817 |
| Comments | Significance level of 0.05. | |
| Method | Fisher Exact | |
| Comments | ||
| Title | Kaplan-Meier Estimate of Duration of Response (DOR) as of 19 October 2015 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomized participants who had a confirmed response |
| Arm/Group Title | Ganetespib and Docetaxel | Docetaxel |
|---|---|---|
| Arm/Group Description | 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. | Docetaxel (75 mg/m^2) was administered on Day 1 of a 3-week treatment cycle by 1-hour IV infusion. |
| Measure Participants | 46 | 54 |
| Median (95% Confidence Interval) [months] |
5.8
|
5.8
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Ganetespib and Docetaxel, Docetaxel |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0111 |
| Comments | Significance level of 0.05. | |
| Method | Log Rank | |
| Comments | P-value was from stratified log-rank test (strata: screening LDH, screening ECOG and geographic region). | |
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 2.344 | |
| Confidence Interval |
(2-Sided) 95% 1.207 to 4.551 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Progression Free Survival (PFS) in Participants With an Elevated Screening Lactate Dehydrogenase (eLDH) as of 19 October 2015 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomized participants who had an elevated screening LDH |
| Arm/Group Title | Ganetespib and Docetaxel | Docetaxel |
|---|---|---|
| Arm/Group Description | 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. | Docetaxel (75 mg/m^2) was administered on Day 1 of a 3-week treatment cycle by 1-hour IV infusion. |
| Measure Participants | 99 | 98 |
| Median (95% Confidence Interval) [months] |
3.0
|
2.8
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Ganetespib and Docetaxel, Docetaxel |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5191 |
| Comments | Significance level of 0.05. | |
| Method | Log Rank | |
| Comments | P-value was from stratified log-rank test (strata: screening ECOG and geographic region). | |
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.112 | |
| Confidence Interval |
(2-Sided) 95% 0.797 to 1.551 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Objective Response Rate (ORR) in Participants With an Elevated Screening Lactate Dehydrogenase (eLDH) as of 19 October 2015 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Ganetespib and Docetaxel | Docetaxel |
|---|---|---|
| Arm/Group Description | 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. | Docetaxel (75 mg/m^2) was administered on Day 1 of a 3-week treatment cycle by 1-hour IV infusion. |
| Measure Participants | 0 | 0 |
| Title | Disease Control Rate (DCR) in Participants With an Elevated Screening Lactate Dehydrogenase (eLDH) as of 19 October 2015 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Ganetespib and Docetaxel | Docetaxel |
|---|---|---|
| Arm/Group Description | 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. | Docetaxel (75 mg/m^2) was administered on Day 1 of a 3-week treatment cycle by 1-hour IV infusion. |
| Measure Participants | 0 | 0 |
| Title | Kaplan-Meier Estimate for Time to Emergence of New Metastatic Lesion (TNL) as of 19 October 2015 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomized participants |
| Arm/Group Title | Ganetespib and Docetaxel | Docetaxel |
|---|---|---|
| Arm/Group Description | 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. | Docetaxel (75 mg/m^2) was administered on Day 1 of a 3-week treatment cycle by 1-hour IV infusion. |
| Measure Participants | 335 | 337 |
| Median (95% Confidence Interval) [months] |
8.1
|
8.7
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Ganetespib and Docetaxel, Docetaxel |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1343 |
| Comments | Significance level of 0.05. | |
| Method | Log Rank | |
| Comments | Stratified log-rank test (strata: screening LDH, screening ECOG and geographic region). | |
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.233 | |
| Confidence Interval |
(2-Sided) 95% 0.937 to 1.621 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Participants With Progressive Disease Due to Any New Metastatic Lesion as of 19 October 2015 |
|---|---|
| Description | Progressive disease was due to either new metastatic lesions only or new metastatic lesions and target tumor growth. |
| Time Frame | up to 36 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomized participants |
| Arm/Group Title | Ganetespib and Docetaxel | Docetaxel |
|---|---|---|
| Arm/Group Description | 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. | Docetaxel (75 mg/m^2) was administered on Day 1 of a 3-week treatment cycle by 1-hour IV infusion. |
| Measure Participants | 335 | 337 |
| Number [percentage of participants] |
34.9
10.1%
|
30.6
8.8%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Ganetespib and Docetaxel, Docetaxel |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.250 |
| Comments | Significance level of 0.05. | |
| Method | Fisher Exact | |
| Comments | ||
| Title | Exploratory Biomarker Analyses |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomized |
| Arm/Group Title | Ganetespib and Docetaxel | Docetaxel |
|---|---|---|
| Arm/Group Description | 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. | Docetaxel (75 mg/m^2) was administered on Day 1 of a 3-week treatment cycle by 1-hour IV infusion. |
| Measure Participants | 0 | 0 |
| Title | Participants With Treatment-Emergent Adverse Events as of 23 December 2015 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population |
| Arm/Group Title | Ganetespib and Docetaxel | Docetaxel |
|---|---|---|
| Arm/Group Description | 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. | Docetaxel (75 mg/m^2) was administered on Day 1 of a 3-week treatment cycle by 1-hour IV infusion. |
| Measure Participants | 338 | 342 |
| >=1 AE |
317
91.4%
|
307
88%
|
| >=1 AE with CTCAE grade of 3 or 4 |
222
64%
|
184
52.7%
|
| >=1 SAE |
139
40.1%
|
107
30.7%
|
| >=1 AE leading to dose reduction |
61
17.6%
|
37
10.6%
|
| >=1 AE leading to delayed dose |
125
36%
|
55
15.8%
|
| >=1 AE leading to study drug discontinuation |
31
8.9%
|
36
10.3%
|
| >=1 SAE leading to study drug discontinuation |
19
5.5%
|
15
4.3%
|
| >=1 SAE leading to hospitalization |
109
31.4%
|
87
24.9%
|
| >=1 SAE with outcome of death |
40
11.5%
|
30
8.6%
|
| >=1 AE with first occurrence during Cycle 1-2 |
280
80.7%
|
280
80.2%
|
| >=1 AE with first occurrence during Cycle 1-4 |
304
87.6%
|
299
85.7%
|
| >=1 AE with first occurrence during Cycle 1-6 |
312
89.9%
|
302
86.5%
|
| Title | Patient-Reported Quality of Life as Measured by the European Quality Of Life - Five Dimensions - Three Levels (EQ-5D-3L) Survey |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Ganetespib and Docetaxel | Docetaxel |
|---|---|---|
| Arm/Group Description | 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. | Docetaxel (75 mg/m^2) was administered on Day 1 of a 3-week treatment cycle by 1-hour IV infusion. |
| Measure Participants | 0 | 0 |
| Title | Patient-Reported Symptom Improvement as Measured by the Functional Assessment of Cancer Therapy - Lung (FACT-L) Version 4 Test |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomized participants |
| Arm/Group Title | Ganetespib and Docetaxel | Docetaxel |
|---|---|---|
| Arm/Group Description | 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. | Docetaxel (75 mg/m^2) was administered on Day 1 of a 3-week treatment cycle by 1-hour IV infusion. |
| Measure Participants | 0 | 0 |
Adverse Events
| Time Frame | up to 36 months | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | Docetaxel | Ganetespib and Docetaxel | ||
| Arm/Group Description | Docetaxel (75 mg/m^2) was administered on Day 1 of a 3-week treatment cycle by 1-hour IV infusion. | 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. | ||
All Cause Mortality |
||||
| Docetaxel | Ganetespib and Docetaxel | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Docetaxel | Ganetespib and Docetaxel | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 107/342 (31.3%) | 139/338 (41.1%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 3/342 (0.9%) | 3 | 6/338 (1.8%) | 6 |
| Febrile neutropenia | 11/342 (3.2%) | 11 | 19/338 (5.6%) | 20 |
| Leukopenia | 1/342 (0.3%) | 1 | 2/338 (0.6%) | 2 |
| Neutropenia | 10/342 (2.9%) | 15 | 12/338 (3.6%) | 14 |
| Cardiac disorders | ||||
| Atrial fibrillation | 1/342 (0.3%) | 1 | 2/338 (0.6%) | 2 |
| Bradycardia | 0/342 (0%) | 0 | 1/338 (0.3%) | 1 |
| Cardiac arrest | 0/342 (0%) | 0 | 1/338 (0.3%) | 1 |
| Cardiac failure | 0/342 (0%) | 0 | 1/338 (0.3%) | 1 |
| Cardiac tamponade | 0/342 (0%) | 0 | 1/338 (0.3%) | 2 |
| Cardiopulmonary failure | 0/342 (0%) | 0 | 1/338 (0.3%) | 1 |
| Ischaemic cardiomyopathy | 1/342 (0.3%) | 1 | 0/338 (0%) | 0 |
| Myocardial infarction | 0/342 (0%) | 0 | 1/338 (0.3%) | 1 |
| Pericardial effusion | 1/342 (0.3%) | 1 | 3/338 (0.9%) | 3 |
| Pericarditis | 1/342 (0.3%) | 1 | 0/338 (0%) | 0 |
| Tachycardia | 0/342 (0%) | 0 | 1/338 (0.3%) | 1 |
| Ear and labyrinth disorders | ||||
| Vertigo | 0/342 (0%) | 0 | 1/338 (0.3%) | 1 |
| Eye disorders | ||||
| Retinal detachment | 1/342 (0.3%) | 1 | 0/338 (0%) | 0 |
| Gastrointestinal disorders | ||||
| Abdominal pain | 0/342 (0%) | 0 | 1/338 (0.3%) | 1 |
| Colitis ischaemic | 1/342 (0.3%) | 1 | 0/338 (0%) | 0 |
| Constipation | 2/342 (0.6%) | 2 | 1/338 (0.3%) | 1 |
| Diarrhoea | 2/342 (0.6%) | 2 | 15/338 (4.4%) | 15 |
| Dry mouth | 0/342 (0%) | 0 | 1/338 (0.3%) | 1 |
| Gastric perforation | 0/342 (0%) | 0 | 1/338 (0.3%) | 1 |
| Gastrointestinal disorder | 0/342 (0%) | 0 | 1/338 (0.3%) | 1 |
| Haematemesis | 0/342 (0%) | 0 | 1/338 (0.3%) | 1 |
| Ileus | 1/342 (0.3%) | 1 | 0/338 (0%) | 0 |
| Ileus paralytic | 0/342 (0%) | 0 | 1/338 (0.3%) | 1 |
| Intestinal perforation | 0/342 (0%) | 0 | 1/338 (0.3%) | 1 |
| Large intestinal obstruction | 0/342 (0%) | 0 | 1/338 (0.3%) | 1 |
| Mesenteric artery thrombosis | 0/342 (0%) | 0 | 1/338 (0.3%) | 1 |
| Nausea | 1/342 (0.3%) | 1 | 1/338 (0.3%) | 1 |
| Oesophageal stenosis | 0/342 (0%) | 0 | 1/338 (0.3%) | 1 |
| Stomatitis | 1/342 (0.3%) | 1 | 1/338 (0.3%) | 1 |
| Subileus | 1/342 (0.3%) | 2 | 0/338 (0%) | 0 |
| Upper gastrointestinal haemorrhage | 1/342 (0.3%) | 1 | 0/338 (0%) | 0 |
| Vomiting | 2/342 (0.6%) | 2 | 2/338 (0.6%) | 3 |
| General disorders | ||||
| Asthenia | 1/342 (0.3%) | 1 | 7/338 (2.1%) | 9 |
| Chest pain | 3/342 (0.9%) | 3 | 0/338 (0%) | 0 |
| Death | 4/342 (1.2%) | 4 | 2/338 (0.6%) | 2 |
| Fatigue | 2/342 (0.6%) | 2 | 1/338 (0.3%) | 1 |
| General physical health deterioration | 2/342 (0.6%) | 2 | 5/338 (1.5%) | 6 |
| Multi-organ failure | 1/342 (0.3%) | 1 | 0/338 (0%) | 0 |
| Non-cardiac chest pain | 1/342 (0.3%) | 1 | 0/338 (0%) | 0 |
| Oedema peripheral | 1/342 (0.3%) | 1 | 0/338 (0%) | 0 |
| Pain | 1/342 (0.3%) | 1 | 0/338 (0%) | 0 |
| Pyrexia | 0/342 (0%) | 0 | 3/338 (0.9%) | 3 |
| Strangulated hernia | 1/342 (0.3%) | 1 | 0/338 (0%) | 0 |
| Sudden cardiac death | 3/342 (0.9%) | 3 | 0/338 (0%) | 0 |
| Sudden death | 0/342 (0%) | 0 | 3/338 (0.9%) | 3 |
| Hepatobiliary disorders | ||||
| Hepatitis toxic | 1/342 (0.3%) | 1 | 0/338 (0%) | 0 |
| Immune system disorders | ||||
| Drug hypersensitivity | 1/342 (0.3%) | 1 | 0/338 (0%) | 0 |
| Immunodeficiency | 0/342 (0%) | 0 | 1/338 (0.3%) | 1 |
| Infections and infestations | ||||
| Anal abscess | 0/342 (0%) | 0 | 1/338 (0.3%) | 1 |
| Bacteraemia | 0/342 (0%) | 0 | 1/338 (0.3%) | 1 |
| Bronchitis | 4/342 (1.2%) | 4 | 0/338 (0%) | 0 |
| Bronchopneumonia | 1/342 (0.3%) | 1 | 5/338 (1.5%) | 5 |
| Bronchopulmonary aspergillosis | 0/342 (0%) | 0 | 1/338 (0.3%) | 1 |
| Cellulitis | 1/342 (0.3%) | 1 | 0/338 (0%) | 0 |
| Device related infection | 0/342 (0%) | 0 | 2/338 (0.6%) | 2 |
| Device related sepsis | 1/342 (0.3%) | 1 | 0/338 (0%) | 0 |
| Diverticulitis | 0/342 (0%) | 0 | 1/338 (0.3%) | 1 |
| Empyema | 1/342 (0.3%) | 1 | 0/338 (0%) | 0 |
| Erysipelas | 0/342 (0%) | 0 | 1/338 (0.3%) | 1 |
| Escherichia bacteraemia | 1/342 (0.3%) | 1 | 0/338 (0%) | 0 |
| Gastroenteritis | 1/342 (0.3%) | 1 | 0/338 (0%) | 0 |
| Infection | 1/342 (0.3%) | 1 | 3/338 (0.9%) | 3 |
| Lower respiratory tract infection | 1/342 (0.3%) | 1 | 3/338 (0.9%) | 3 |
| Lung infection | 0/342 (0%) | 0 | 1/338 (0.3%) | 1 |
| Neutropenic sepsis | 1/342 (0.3%) | 1 | 2/338 (0.6%) | 2 |
| Oesophageal candidiasis | 1/342 (0.3%) | 1 | 0/338 (0%) | 0 |
| Oral candidiasis | 0/342 (0%) | 0 | 1/338 (0.3%) | 1 |
| Perirectal abscess | 0/342 (0%) | 0 | 1/338 (0.3%) | 1 |
| Peritonsillar abscess | 1/342 (0.3%) | 1 | 1/338 (0.3%) | 1 |
| Pneumonia | 2/342 (0.6%) | 2 | 12/338 (3.6%) | 12 |
| Pseudomembranous colitis | 0/342 (0%) | 0 | 1/338 (0.3%) | 1 |
| Pulmonary tuberculosis | 0/342 (0%) | 0 | 1/338 (0.3%) | 1 |
| Respiratory tract infection | 2/342 (0.6%) | 2 | 3/338 (0.9%) | 3 |
| Sepsis | 1/342 (0.3%) | 1 | 4/338 (1.2%) | 4 |
| Sinusitis | 0/342 (0%) | 0 | 1/338 (0.3%) | 1 |
| Skin infection | 0/342 (0%) | 0 | 1/338 (0.3%) | 1 |
| Subcutaneous abscess | 1/342 (0.3%) | 1 | 0/338 (0%) | 0 |
| Urinary tract infection | 0/342 (0%) | 0 | 1/338 (0.3%) | 1 |
| Urosepsis | 0/342 (0%) | 0 | 1/338 (0.3%) | 1 |
| Injury, poisoning and procedural complications | ||||
| Ankle fracture | 0/342 (0%) | 0 | 2/338 (0.6%) | 2 |
| Concussion | 0/342 (0%) | 0 | 1/338 (0.3%) | 1 |
| Hip fracture | 0/342 (0%) | 0 | 1/338 (0.3%) | 1 |
| Infusion related reaction | 2/342 (0.6%) | 2 | 3/338 (0.9%) | 4 |
| Joint dislocation | 0/342 (0%) | 0 | 1/338 (0.3%) | 1 |
| Investigations | ||||
| Electrocardiogram QT prolonged | 0/342 (0%) | 0 | 1/338 (0.3%) | 1 |
| White blood cell count decreased | 1/342 (0.3%) | 1 | 0/338 (0%) | 0 |
| Hyponatraemia | 0/342 (0%) | 0 | 2/338 (0.6%) | 2 |
| Hypovolaemia | 0/342 (0%) | 0 | 1/338 (0.3%) | 1 |
| Metabolism and nutrition disorders | ||||
| Dehydration | 3/342 (0.9%) | 3 | 2/338 (0.6%) | 2 |
| Hyperkalaemia | 0/342 (0%) | 0 | 1/338 (0.3%) | 1 |
| Metabolic acidosis | 0/342 (0%) | 0 | 1/338 (0.3%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 1/342 (0.3%) | 1 | 0/338 (0%) | 0 |
| Back pain | 1/342 (0.3%) | 1 | 1/338 (0.3%) | 1 |
| Bone pain | 0/342 (0%) | 0 | 1/338 (0.3%) | 1 |
| Musculoskeletal chest pain | 0/342 (0%) | 0 | 1/338 (0.3%) | 1 |
| Pain in extremity | 1/342 (0.3%) | 2 | 0/338 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Cancer pain | 0/342 (0%) | 0 | 1/338 (0.3%) | 1 |
| Neoplasm progression | 11/342 (3.2%) | 11 | 16/338 (4.7%) | 16 |
| Nervous system disorders | ||||
| Aphasia | 0/342 (0%) | 0 | 1/338 (0.3%) | 1 |
| Cerebrovascular accident | 1/342 (0.3%) | 1 | 0/338 (0%) | 0 |
| Hypersomnia | 0/342 (0%) | 0 | 1/338 (0.3%) | 1 |
| Ischaemic stroke | 0/342 (0%) | 0 | 1/338 (0.3%) | 1 |
| Loss of consciousness | 0/342 (0%) | 0 | 1/338 (0.3%) | 1 |
| Paraesthesia | 1/342 (0.3%) | 1 | 0/338 (0%) | 0 |
| Peripheral sensorimotor neuropathy | 1/342 (0.3%) | 1 | 0/338 (0%) | 0 |
| Seizure | 1/342 (0.3%) | 1 | 0/338 (0%) | 0 |
| Somnolence | 1/342 (0.3%) | 1 | 0/338 (0%) | 0 |
| Syncope | 1/342 (0.3%) | 1 | 4/338 (1.2%) | 4 |
| Psychiatric disorders | ||||
| Completed suicide | 0/342 (0%) | 0 | 1/338 (0.3%) | 1 |
| Confusional state | 0/342 (0%) | 0 | 1/338 (0.3%) | 1 |
| Depression | 1/342 (0.3%) | 1 | 0/338 (0%) | 0 |
| Mental status changes | 1/342 (0.3%) | 1 | 0/338 (0%) | 0 |
| Psychotic disorder | 0/342 (0%) | 0 | 1/338 (0.3%) | 1 |
| Renal and urinary disorders | ||||
| Acute kidney injury | 0/342 (0%) | 0 | 2/338 (0.6%) | 2 |
| Haematuria | 1/342 (0.3%) | 1 | 0/338 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Acute respiratory distress syndrome | 1/342 (0.3%) | 1 | 0/338 (0%) | 0 |
| Acute respiratory failure | 1/342 (0.3%) | 1 | 2/338 (0.6%) | 2 |
| Aspiration | 1/342 (0.3%) | 1 | 0/338 (0%) | 0 |
| Atelectasis | 0/342 (0%) | 0 | 1/338 (0.3%) | 1 |
| Chronic obstructive pulmonary disease | 1/342 (0.3%) | 1 | 0/338 (0%) | 0 |
| Cough | 0/342 (0%) | 0 | 1/338 (0.3%) | 1 |
| Dyspnoea | 11/342 (3.2%) | 12 | 9/338 (2.7%) | 9 |
| Haemoptysis | 1/342 (0.3%) | 1 | 0/338 (0%) | 0 |
| Pleural effusion | 4/342 (1.2%) | 6 | 3/338 (0.9%) | 3 |
| Pneumothorax | 1/342 (0.3%) | 1 | 2/338 (0.6%) | 2 |
| Pulmonary embolism | 5/342 (1.5%) | 5 | 3/338 (0.9%) | 3 |
| Pulmonary fibrosis | 0/342 (0%) | 0 | 1/338 (0.3%) | 1 |
| Respiratory distress | 1/342 (0.3%) | 1 | 1/338 (0.3%) | 1 |
| Respiratory failure | 0/342 (0%) | 0 | 2/338 (0.6%) | 2 |
| Pneumonitis | 1/342 (0.3%) | 1 | 1/338 (0.3%) | 1 |
| Skin and subcutaneous tissue disorders | ||||
| Palmar-plantar erythrodysaesthesia syndrome | 1/342 (0.3%) | 1 | 0/338 (0%) | 0 |
| Surgical and medical procedures | ||||
| Cancer surgery | 1/342 (0.3%) | 1 | 0/338 (0%) | 0 |
| Vascular disorders | ||||
| Deep vein thrombosis | 0/342 (0%) | 0 | 1/338 (0.3%) | 1 |
| Embolism | 0/342 (0%) | 0 | 2/338 (0.6%) | 2 |
| Hypertension | 0/342 (0%) | 0 | 1/338 (0.3%) | 1 |
| Hypotension | 2/342 (0.6%) | 2 | 2/338 (0.6%) | 2 |
| Jugular vein thrombosis | 0/342 (0%) | 0 | 1/338 (0.3%) | 1 |
| Superior vena cava syndrome | 0/342 (0%) | 0 | 2/338 (0.6%) | 2 |
| Thrombosis | 2/342 (0.6%) | 2 | 0/338 (0%) | 0 |
| Venous thrombosis limb | 1/342 (0.3%) | 1 | 0/338 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||
| Docetaxel | Ganetespib and Docetaxel | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 293/342 (85.7%) | 308/338 (91.1%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 70/342 (20.5%) | 144 | 59/338 (17.5%) | 106 |
| Leukopenia | 18/342 (5.3%) | 54 | 20/338 (5.9%) | 39 |
| Neutropenia | 94/342 (27.5%) | 255 | 109/338 (32.2%) | 243 |
| Gastrointestinal disorders | ||||
| Constipation | 26/342 (7.6%) | 31 | 35/338 (10.4%) | 41 |
| Diarrhoea | 47/342 (13.7%) | 64 | 149/338 (44.1%) | 327 |
| Nausea | 68/342 (19.9%) | 103 | 59/338 (17.5%) | 86 |
| Stomatitis | 36/342 (10.5%) | 52 | 32/338 (9.5%) | 40 |
| Vomiting | 23/342 (6.7%) | 27 | 36/338 (10.7%) | 46 |
| General disorders | ||||
| Asthenia | 48/342 (14%) | 109 | 51/338 (15.1%) | 100 |
| Chest pain | 17/342 (5%) | 20 | 19/338 (5.6%) | 26 |
| Fatigue | 72/342 (21.1%) | 123 | 79/338 (23.4%) | 130 |
| Oedema peripheral | 29/342 (8.5%) | 30 | 28/338 (8.3%) | 39 |
| Pyrexia | 19/342 (5.6%) | 30 | 26/338 (7.7%) | 33 |
| Injury, poisoning and procedural complications | ||||
| Infusion related reaction | 11/342 (3.2%) | 13 | 17/338 (5%) | 32 |
| Investigations | ||||
| Weight decreased | 18/342 (5.3%) | 22 | 38/338 (11.2%) | 50 |
| Metabolism and nutrition disorders | ||||
| Decreased appetite | 35/342 (10.2%) | 49 | 52/338 (15.4%) | 66 |
| Hyponatraemia | 9/342 (2.6%) | 20 | 26/338 (7.7%) | 46 |
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 20/342 (5.8%) | 35 | 17/338 (5%) | 24 |
| Back pain | 14/342 (4.1%) | 19 | 24/338 (7.1%) | 28 |
| Bone pain | 17/342 (5%) | 24 | 19/338 (5.6%) | 26 |
| Myalgia | 28/342 (8.2%) | 52 | 38/338 (11.2%) | 64 |
| Pain in extremity | 15/342 (4.4%) | 19 | 18/338 (5.3%) | 23 |
| Nervous system disorders | ||||
| Dizziness | 21/342 (6.1%) | 30 | 24/338 (7.1%) | 41 |
| Headache | 17/342 (5%) | 23 | 22/338 (6.5%) | 30 |
| Neuropathy peripheral | 33/342 (9.6%) | 52 | 41/338 (12.1%) | 63 |
| Peripheral sensory neuropathy | 23/342 (6.7%) | 29 | 15/338 (4.4%) | 18 |
| Psychiatric disorders | ||||
| Insomnia | 8/342 (2.3%) | 8 | 23/338 (6.8%) | 23 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 31/342 (9.1%) | 36 | 34/338 (10.1%) | 45 |
| Dyspnoea | 41/342 (12%) | 56 | 55/338 (16.3%) | 59 |
| Skin and subcutaneous tissue disorders | ||||
| Alopecia | 84/342 (24.6%) | 98 | 76/338 (22.5%) | 93 |
| Rash | 16/342 (4.7%) | 20 | 19/338 (5.6%) | 21 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Sponsor has the right, 60 days before submission for publication, to review disclosures and require deletion of its confidential information, excluding the study results. Public disclosure shall be delayed for up to 60 additional days in order for the Sponsor to file a patent application, if needed. Single center publications will be postponed until after disclosure of pooled data (all sites), or, for a period of 18 months from study completion/termination at all participating sites.
Results Point of Contact
| Name/Title | President, Chief Executive Officer |
|---|---|
| Organization | Synta Pharmaceuticals |
| Phone | 781-541-7261 |
Responsible Party:
Synta Pharmaceuticals Corp.
ClinicalTrials.gov Identifier:
NCT01798485
Other Study ID Numbers:
- 9090-14
- 2012-004349-34
First Posted:
Feb 25, 2013
Last Update Posted:
Jul 1, 2016
Last Verified:
May 1, 2016