Trial Review

Did you know?

The ANZCTR now automatically displays published trial results and simplifies the addition of trial documents such as unpublished protocols and statistical analysis plans.

These enhancements will offer a more comprehensive view of trials, regardless of whether their results are positive, negative, or inconclusive.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03061812




Registration number
NCT03061812
Ethics application status
Date submitted
20/02/2017
Date registered
23/02/2017
Date last updated
23/02/2021

Titles & IDs
Public title
Study Comparing Rovalpituzumab Tesirine Versus Topotecan in Subjects With Advanced or Metastatic Small Cell Lung Cancer With High Levels of Delta-like Protein 3 (DLL3) and Who Have First Disease Progression During or Following Front-line Platinum-based Chemotherapy (TAHOE)
Scientific title
A Randomized, Open-Label, Multicenter, Phase 3 Study of Rovalpituzumab Tesirine Compared With Topotecan for Subjects With Advanced or Metastatic DLL3high Small Cell Lung Cancer (SCLC) Who Have First Disease Progression During or Following Front-Line Platinum-Based Chemotherapy (TAHOE)
Secondary ID [1] 0 0
2016-003726-17
Secondary ID [2] 0 0
M16-289
Universal Trial Number (UTN)
Trial acronym
TAHOE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Small Cell Lung Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Small cell

Intervention/exposure
Study type
Interventional(has expanded access)
Description of intervention(s) / exposure
Treatment: Drugs - Rovalpituzumab tesirine
Treatment: Drugs - Topotecan
Treatment: Drugs - Dexamethasone

Experimental: Rovalpituzumab tesirine - Rovalpituzumab tesirine IV administration (dosing based on actual body weight) on Day 1 of a 42-day cycle for 2 cycles, with up to 2 additional cycles permitted.

Dexamethasone coadministered orally (PO) twice daily at a dose of 8 mg on Day -1, Day 1, and Day 2 of each 42-day cycle in which rovalpituzumab tesirine is administered.

Active comparator: Topotecan - Topotecan given as an intravenous (IV) infusion over 30 minutes at a dose of 1.5 mg/m\^2 on Days 1 to 5 of each 21-day cycle.


Treatment: Drugs: Rovalpituzumab tesirine
Powder for solution for infusion in vials.

Treatment: Drugs: Topotecan
Powder or solution for infusion in vials. Topotecan is commercially available as both a powder and solution for infusion. Availability will vary by region.

Treatment: Drugs: Dexamethasone
Oral tablet.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Survival (OS)
Timepoint [1] 0 0
From randomization until the end of study; median time on follow-up was 20 and 20.6 months for the topotecan and rovalpituzumab tesirine arms, respectively.
Secondary outcome [1] 0 0
Progression Free Survival (PFS)
Timepoint [1] 0 0
From randomization until the end of study; median time on follow-up was 20 and 20.6 months for the topotecan and rovalpituzumab tesirine arms, respectively.
Secondary outcome [2] 0 0
Change From Baseline of the Physical Functioning Scale Score in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 15-Palliative Care (EORTC QLQ-C15-PAL) at Week 7
Timepoint [2] 0 0
Baseline, Week 7
Secondary outcome [3] 0 0
Objective Response Rate (ORR)
Timepoint [3] 0 0
Radiographic tumor assessments were conducted at baseline, every 6 weeks for 30 weeks, then every 9 weeks until progression or death; median time on follow-up was 20 and 20.6 months for the topotecan and rovalpituzumab tesirine arms, respectively.
Secondary outcome [4] 0 0
Clinical Benefit Rate (CBR)
Timepoint [4] 0 0
Radiographic tumor assessments were conducted at baseline, every 6 weeks for 30 weeks, then every 9 weeks until progression or death; median time on follow-up was 20 and 20.6 months for the topotecan and rovalpituzumab tesirine arms, respectively.
Secondary outcome [5] 0 0
Duration of Objective Response (DOR)
Timepoint [5] 0 0
Radiographic tumor assessments were conducted at baseline, every 6 weeks for 30 weeks, then every 9 weeks until progression or death; median time on follow-up was 20 and 20.6 months for the topotecan and rovalpituzumab tesirine arms, respectively.

Eligibility
Key inclusion criteria
* Participant must have histologically or cytologically confirmed advanced or metastatic Small Cell Lung Cancer (SCLC) with documented first disease progression during or following front-line platinum-based systemic regimen
* Tumor must have high Delta-like protein 3 (DLL3) expression defined as having = 75% tumor cells staining positive according to the VENTANA DLL3 (SP347) IHC Assay.
* Participant must have measurable disease, as defined per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
* Participant must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
* Participant must have recovery to Grade 0 or 1 of any clinically significant toxicity (excluding alopecia) prior to initiation of study drug administration.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Participant has a documented history of a cerebral vascular event (stroke or transient ischemic attack), unstable angina, myocardial infarction, or cardiac symptoms consistent with New York Heart Association Class (NYHA) III - IV within 6 months prior to their first dose of study drug.
* Participant has known leptomeningeal metastases.
* Participant has received more than one prior systemic therapy regimen for SCLC.
* Participant had a serious infection within 2 weeks prior to randomization, including any Grade 3 or higher viral, bacterial, or fungal infection.
* Participant has a history of active malignancies other than SCLC within the past 2 years prior to study entry, with the exception of in situ cancer which was curatively treated.
* Participant had prior exposure to topotecan, irinotecan or any other topoisomerase I inhibitors.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
11/04/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
12/02/2020
Sample size
Target
Accrual to date
Final
444
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
Blacktown Hospital /ID# 158907 - Blacktown
Recruitment hospital [2] 0 0
St George Hospital /ID# 158855 - Kogarah
Recruitment hospital [3] 0 0
Southern Medical Day Care Ctr /ID# 158853 - Wollongong
Recruitment hospital [4] 0 0
The Prince Charles Hospital /ID# 158897 - Chermside
Recruitment hospital [5] 0 0
Ballarat Health Service /ID# 158904 - Ballarat
Recruitment hospital [6] 0 0
Austin Hospital /ID# 158898 - Heidelberg
Recruitment postcode(s) [1] 0 0
2148 - Blacktown
Recruitment postcode(s) [2] 0 0
2217 - Kogarah
Recruitment postcode(s) [3] 0 0
2500 - Wollongong
Recruitment postcode(s) [4] 0 0
4032 - Chermside
Recruitment postcode(s) [5] 0 0
3350 - Ballarat
Recruitment postcode(s) [6] 0 0
3084 - Heidelberg
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arkansas
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Delaware
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Georgia
Country [7] 0 0
United States of America
State/province [7] 0 0
Idaho
Country [8] 0 0
United States of America
State/province [8] 0 0
Illinois
Country [9] 0 0
United States of America
State/province [9] 0 0
Indiana
Country [10] 0 0
United States of America
State/province [10] 0 0
Kentucky
Country [11] 0 0
United States of America
State/province [11] 0 0
Louisiana
Country [12] 0 0
United States of America
State/province [12] 0 0
Massachusetts
Country [13] 0 0
United States of America
State/province [13] 0 0
Michigan
Country [14] 0 0
United States of America
State/province [14] 0 0
Nebraska
Country [15] 0 0
United States of America
State/province [15] 0 0
Ohio
Country [16] 0 0
United States of America
State/province [16] 0 0
Oregon
Country [17] 0 0
United States of America
State/province [17] 0 0
Pennsylvania
Country [18] 0 0
United States of America
State/province [18] 0 0
Texas
Country [19] 0 0
United States of America
State/province [19] 0 0
Vermont
Country [20] 0 0
United States of America
State/province [20] 0 0
Washington
Country [21] 0 0
United States of America
State/province [21] 0 0
West Virginia
Country [22] 0 0
Belarus
State/province [22] 0 0
Bobruisk
Country [23] 0 0
Belarus
State/province [23] 0 0
Lesnoy
Country [24] 0 0
Belarus
State/province [24] 0 0
Mogilev
Country [25] 0 0
Belgium
State/province [25] 0 0
Bruxelles-Capitale
Country [26] 0 0
Belgium
State/province [26] 0 0
Hainaut
Country [27] 0 0
Belgium
State/province [27] 0 0
Brussels
Country [28] 0 0
Belgium
State/province [28] 0 0
Haine Saint Paul
Country [29] 0 0
Belgium
State/province [29] 0 0
Leuven
Country [30] 0 0
Belgium
State/province [30] 0 0
Liege
Country [31] 0 0
Belgium
State/province [31] 0 0
Montigny-le-tilleul
Country [32] 0 0
Brazil
State/province [32] 0 0
Rio Grande Do Norte
Country [33] 0 0
Brazil
State/province [33] 0 0
Rio Grande Do Sul
Country [34] 0 0
Brazil
State/province [34] 0 0
Sao Paulo
Country [35] 0 0
Brazil
State/province [35] 0 0
Rio de Janeiro
Country [36] 0 0
Bulgaria
State/province [36] 0 0
Sofia
Country [37] 0 0
Canada
State/province [37] 0 0
Alberta
Country [38] 0 0
Canada
State/province [38] 0 0
Ontario
Country [39] 0 0
Canada
State/province [39] 0 0
Quebec
Country [40] 0 0
China
State/province [40] 0 0
Jilin
Country [41] 0 0
Croatia
State/province [41] 0 0
Grad Zagreb
Country [42] 0 0
Croatia
State/province [42] 0 0
Primorsko-goranska Zupanija
Country [43] 0 0
Czechia
State/province [43] 0 0
Praha 4
Country [44] 0 0
Czechia
State/province [44] 0 0
Pribram
Country [45] 0 0
Czechia
State/province [45] 0 0
Benesov
Country [46] 0 0
Czechia
State/province [46] 0 0
Horovice
Country [47] 0 0
Czechia
State/province [47] 0 0
Liberec
Country [48] 0 0
Denmark
State/province [48] 0 0
Hovedstaden
Country [49] 0 0
Denmark
State/province [49] 0 0
Syddanmark
Country [50] 0 0
Denmark
State/province [50] 0 0
Copenhagen
Country [51] 0 0
France
State/province [51] 0 0
Gironde
Country [52] 0 0
France
State/province [52] 0 0
Provence-Alpes-Cote-d Azur
Country [53] 0 0
France
State/province [53] 0 0
Rhone
Country [54] 0 0
France
State/province [54] 0 0
Val-de-Marne
Country [55] 0 0
France
State/province [55] 0 0
Paris
Country [56] 0 0
France
State/province [56] 0 0
Rennes
Country [57] 0 0
Germany
State/province [57] 0 0
Sachsen-Anhalt
Country [58] 0 0
Germany
State/province [58] 0 0
Berlin
Country [59] 0 0
Germany
State/province [59] 0 0
Gauting
Country [60] 0 0
Germany
State/province [60] 0 0
Grosshansdorf
Country [61] 0 0
Germany
State/province [61] 0 0
Heidelberg
Country [62] 0 0
Germany
State/province [62] 0 0
Kassel
Country [63] 0 0
Germany
State/province [63] 0 0
Löwenstein
Country [64] 0 0
Greece
State/province [64] 0 0
Athens
Country [65] 0 0
Greece
State/province [65] 0 0
Ioannina
Country [66] 0 0
Greece
State/province [66] 0 0
Thessaloniki
Country [67] 0 0
Hungary
State/province [67] 0 0
Pest
Country [68] 0 0
Hungary
State/province [68] 0 0
Budapest
Country [69] 0 0
Hungary
State/province [69] 0 0
Debrecen
Country [70] 0 0
Hungary
State/province [70] 0 0
Farkasgyepu
Country [71] 0 0
Hungary
State/province [71] 0 0
Gyor
Country [72] 0 0
Hungary
State/province [72] 0 0
Matrahaza
Country [73] 0 0
Italy
State/province [73] 0 0
Arezzo
Country [74] 0 0
Italy
State/province [74] 0 0
Milan
Country [75] 0 0
Italy
State/province [75] 0 0
Orbassano
Country [76] 0 0
Italy
State/province [76] 0 0
Ravenna
Country [77] 0 0
Italy
State/province [77] 0 0
Rome
Country [78] 0 0
Japan
State/province [78] 0 0
Aichi
Country [79] 0 0
Japan
State/province [79] 0 0
Chiba
Country [80] 0 0
Japan
State/province [80] 0 0
Fukuoka
Country [81] 0 0
Japan
State/province [81] 0 0
Hokkaido
Country [82] 0 0
Japan
State/province [82] 0 0
Hyogo
Country [83] 0 0
Japan
State/province [83] 0 0
Ishikawa
Country [84] 0 0
Japan
State/province [84] 0 0
Kanagawa
Country [85] 0 0
Japan
State/province [85] 0 0
Miyagi
Country [86] 0 0
Japan
State/province [86] 0 0
Okayama
Country [87] 0 0
Japan
State/province [87] 0 0
Osaka
Country [88] 0 0
Japan
State/province [88] 0 0
Shizuoka
Country [89] 0 0
Japan
State/province [89] 0 0
Tokushima
Country [90] 0 0
Japan
State/province [90] 0 0
Tokyo
Country [91] 0 0
Japan
State/province [91] 0 0
Wakayama
Country [92] 0 0
Japan
State/province [92] 0 0
Matsusaka-shi MIE
Country [93] 0 0
Japan
State/province [93] 0 0
Yokohama
Country [94] 0 0
Korea, Republic of
State/province [94] 0 0
Busan Gwang Yeogsi
Country [95] 0 0
Korea, Republic of
State/province [95] 0 0
Gyeonggido
Country [96] 0 0
Korea, Republic of
State/province [96] 0 0
Jeonranamdo
Country [97] 0 0
Korea, Republic of
State/province [97] 0 0
Seoul Teugbyeolsi
Country [98] 0 0
Korea, Republic of
State/province [98] 0 0
Cheongju-si
Country [99] 0 0
Korea, Republic of
State/province [99] 0 0
Seoul
Country [100] 0 0
Latvia
State/province [100] 0 0
Riga
Country [101] 0 0
Mexico
State/province [101] 0 0
Michoacan
Country [102] 0 0
Mexico
State/province [102] 0 0
Del. Benito Juárez
Country [103] 0 0
Netherlands
State/province [103] 0 0
Groningen
Country [104] 0 0
Netherlands
State/province [104] 0 0
Harderwijk
Country [105] 0 0
Netherlands
State/province [105] 0 0
Zwolle
Country [106] 0 0
Poland
State/province [106] 0 0
Podkarpackie
Country [107] 0 0
Poland
State/province [107] 0 0
Gdansk
Country [108] 0 0
Poland
State/province [108] 0 0
Gdynia
Country [109] 0 0
Portugal
State/province [109] 0 0
Lisboa
Country [110] 0 0
Portugal
State/province [110] 0 0
Lisbon
Country [111] 0 0
Portugal
State/province [111] 0 0
Matosinhos
Country [112] 0 0
Portugal
State/province [112] 0 0
Porto
Country [113] 0 0
Romania
State/province [113] 0 0
Dolj
Country [114] 0 0
Romania
State/province [114] 0 0
Timis
Country [115] 0 0
Romania
State/province [115] 0 0
Alba
Country [116] 0 0
Russian Federation
State/province [116] 0 0
Moskovskaya Oblast
Country [117] 0 0
Russian Federation
State/province [117] 0 0
Stavropol Skiy Kray
Country [118] 0 0
Russian Federation
State/province [118] 0 0
Arkhangelsk
Country [119] 0 0
Russian Federation
State/province [119] 0 0
Kaluga
Country [120] 0 0
Russian Federation
State/province [120] 0 0
Omsk
Country [121] 0 0
Russian Federation
State/province [121] 0 0
Pushkin
Country [122] 0 0
Russian Federation
State/province [122] 0 0
Smolensk
Country [123] 0 0
Russian Federation
State/province [123] 0 0
St. Petersburg
Country [124] 0 0
Serbia
State/province [124] 0 0
Nisavski Okrug
Country [125] 0 0
Serbia
State/province [125] 0 0
Belgrade
Country [126] 0 0
Serbia
State/province [126] 0 0
Sremska Kamenica
Country [127] 0 0
Singapore
State/province [127] 0 0
Singapore
Country [128] 0 0
Spain
State/province [128] 0 0
Barcelona
Country [129] 0 0
Spain
State/province [129] 0 0
Madrid
Country [130] 0 0
Spain
State/province [130] 0 0
Valencia
Country [131] 0 0
Sweden
State/province [131] 0 0
Vastra Gotalands Lan
Country [132] 0 0
Sweden
State/province [132] 0 0
Uppsala
Country [133] 0 0
Taiwan
State/province [133] 0 0
Tainan
Country [134] 0 0
Taiwan
State/province [134] 0 0
Taipei
Country [135] 0 0
Taiwan
State/province [135] 0 0
Taichung City
Country [136] 0 0
Turkey
State/province [136] 0 0
Ankara
Country [137] 0 0
Turkey
State/province [137] 0 0
Battalgazi/malatya
Country [138] 0 0
Turkey
State/province [138] 0 0
Izmir
Country [139] 0 0
Turkey
State/province [139] 0 0
Kecioren/ankara
Country [140] 0 0
Ukraine
State/province [140] 0 0
Zaporizka Oblast
Country [141] 0 0
Ukraine
State/province [141] 0 0
Chernivtsi
Country [142] 0 0
Ukraine
State/province [142] 0 0
Dnipro
Country [143] 0 0
Ukraine
State/province [143] 0 0
Kharkiv
Country [144] 0 0
Ukraine
State/province [144] 0 0
Kropyvnytskyi
Country [145] 0 0
Ukraine
State/province [145] 0 0
Kryviy RIH
Country [146] 0 0
Ukraine
State/province [146] 0 0
Lutsk
Country [147] 0 0
Ukraine
State/province [147] 0 0
Uzhhorod
Country [148] 0 0
United Kingdom
State/province [148] 0 0
London, City Of
Country [149] 0 0
United Kingdom
State/province [149] 0 0
Boston
Country [150] 0 0
United Kingdom
State/province [150] 0 0
London
Country [151] 0 0
United Kingdom
State/province [151] 0 0
Manchester
Country [152] 0 0
United Kingdom
State/province [152] 0 0
Middlesborough
Country [153] 0 0
United Kingdom
State/province [153] 0 0
Preston

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
AbbVie
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this randomized, open-label, 2-arm, phase 3 study is to assess the efficacy, safety and tolerability of rovalpituzumab tesirine versus topotecan in participants with advanced or metastatic SCLC with high levels of DLL3, who have first disease progression during or following front-line platinum-based chemotherapy.
Trial website
https://clinicaltrials.gov/study/NCT03061812
Trial related presentations / publications
Morgensztern D, Besse B, Greillier L, Santana-Davila R, Ready N, Hann CL, Glisson BS, Farago AF, Dowlati A, Rudin CM, Le Moulec S, Lally S, Yalamanchili S, Wolf J, Govindan R, Carbone DP. Efficacy and Safety of Rovalpituzumab Tesirine in Third-Line and Beyond Patients with DLL3-Expressing, Relapsed/Refractory Small-Cell Lung Cancer: Results From the Phase II TRINITY Study. Clin Cancer Res. 2019 Dec 1;25(23):6958-6966. doi: 10.1158/1078-0432.CCR-19-1133. Epub 2019 Sep 10.
Tanaka K, Isse K, Fujihira T, Takenoyama M, Saunders L, Bheddah S, Nakanishi Y, Okamoto I. Prevalence of Delta-like protein 3 expression in patients with small cell lung cancer. Lung Cancer. 2018 Jan;115:116-120. doi: 10.1016/j.lungcan.2017.11.018. Epub 2017 Nov 22.
Public notes

Contacts
Principal investigator
Name 0 0
AbbVie Inc.
Address 0 0
AbbVie
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT03061812