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) (TAHOE)

Tracking Information
First Submitted Date ICMJE	February 20, 2017
First Posted Date ICMJE	February 23, 2017
Last Update Posted Date	November 6, 2018
Actual Study Start Date ICMJE	April 10, 2017
Estimated Primary Completion Date	September 19, 2019 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: October 10, 2018)	Overall Survival (OS) [ Time Frame: Approximately 34 months ]; Overall Survival (OS) is defined as the time from the date of randomization to the date of death from any cause.
Original Primary Outcome Measures ICMJE; (submitted: February 20, 2017)	Objective response rate (ORR) [ Time Frame: Approximately 23 months ]ORR is defined as the percentage of participants whose best overall response is either complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.; Overall Survival (OS) [ Time Frame: Approximately 34 months ]Overall Survival (OS) is defined as the time from the date of randomization to the date of death from any cause.
Change History	Complete list of historical versions of study NCT03061812 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: October 10, 2018)	Objective Response Rate (ORR) [ Time Frame: Approximately 34 months ]ORR is defined as the percentage of participants whose best overall response is complete response (CR) + partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.; Change from baseline of the Physical functioning scale score in QLQ-C15-PAL [ Time Frame: Approximately 34 months ]European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 15-Palliative Care (EORTC OLQ-C15-PAL) is a questionnaire developed to assess the quality of life of palliative cancer care. Higher scores reflect greater symptom burden.; Progression Free Survival (PFS) [ Time Frame: Approximately 34 months ]PFS is based on independent review of radiographic assessment, defined as the time from randomization to documented disease progression or death from any cause, whichever occurs earlier.; Duration of Objective Response (DOR) [ Time Frame: Approximately 34 months ]DOR is defined as the time between the date of first response (CR or PR, whichever is recorded first) to the date of the first documented tumor progression (per RECIST version 1.1) or death due to any cause, whichever comes first.; Clinical Benefit Rate (CBR) [ Time Frame: Approximately 34 months ]CBR is defined as percentage of participants whose best overall response is complete response (CR) + partial response (PR) + stable disease (SD) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Original Secondary Outcome Measures ICMJE; (submitted: February 20, 2017)	Progression Free Survival (PFS) [ Time Frame: Approximately 34 months ]PFS is based on independent review of radiographic assessment, defined as the time from randomization to documented disease progression or death from any cause, whichever occurs earlier.; Duration of Objective Response (DOR) [ Time Frame: Approximately 34 months ]DOR is defined as the time between the date of first response (CR or PR, whichever is recorded first) to the date of the first documented tumor progression (per RECIST version 1.1) or death due to any cause, whichever comes first.; Change from baseline of the Physical functioning scale score in QLQ-C15-PAL [ Time Frame: Approximately 34 months ]European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 15-Palliative Care (EORTC OLQ-C15-PAL) is a questionnaire developed to assess the quality of life of palliative cancer care. Higher scores reflect greater symptom burden.
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	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)
Official Title ICMJE	A Randomized, Open-label, Multicenter, Phase 3 Study of Rovalpituzumab Tesirine Compared With Topotecan for High DLL3 Expressing Small Cell Lung Cancer (SCLC) Subjects With First Relapse/Recurrence Following Front-Line Platinum-Based Chemotherapy (TAHOE)
Brief Summary	The purpose of this randomized, open-label, 2-arm, Phase 3 study is to assess the assess the efficacy, safety and tolerability of rovalpituzumab tesirine versus topotecan in participants with advanced or metastatic Small Cell Lung Cancer (SCLC) with high levels of delta-like protein 3 (DLL3) and who have first disease progression during or following front-line platinum-based chemotherapy.
Detailed Description	Not Provided
Study Type ICMJE	Interventional
Study Phase	Phase 3
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	Small Cell Lung Cancer
Intervention ICMJE	Drug: Rovalpituzumab tesirine Administered on Day 1 via intravenous infusion in a 42-day cycle for 2 cycles.; Drug: Topotecan Administered on Day 1-5 via intravenous infusion in a 21-day cycle.
Study Arms	Experimental: Rovalpituzumab tesirine Rovalpituzumab tesirine intravenous administration on Day 1 of a 42-Day cycle for 2 cycles. Intervention: Drug: Rovalpituzumab tesirine; Active Comparator: Topotecan Topotecan intravenous on Days 1 through 5 of each 21-Day cycle. Intervention: Drug: Topotecan
Publications *	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.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Recruiting
Estimated Enrollment ICMJE; (submitted: September 28, 2018)	600
Original Estimated Enrollment ICMJE; (submitted: February 20, 2017)	411
Estimated Study Completion Date	September 30, 2021
Estimated Primary Completion Date	September 19, 2019 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	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. 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.
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years and older (Adult, Older Adult)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact: ABBVIE CALL CENTER 847.283.8955 abbvieclinicaltrials@abbvie.com
Listed Location Countries ICMJE	Australia, Belarus, Belgium, Brazil, Bulgaria, Canada, China, Croatia, Czechia, Denmark, France, Germany, Greece, Hungary, Italy, Japan, Korea, Republic of, Latvia, Mexico, Netherlands, Poland, Portugal, Romania, Russian Federation, Serbia, Singapore, Spain, Sweden, Taiwan, Turkey, Ukraine, United Kingdom, United States
Removed Location Countries	Finland
Administrative Information
NCT Number ICMJE	NCT03061812
Other Study ID Numbers ICMJE	M16-289; 2016-003726-17 ( EudraCT Number )
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Studies a U.S. FDA-regulated Drug Product: Yes Studies a U.S. FDA-regulated Device Product: No Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement	Plan to Share IPD: Yes Plan Description: AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols and clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications. Supporting Materials: Study Protocol Supporting Materials: Statistical Analysis Plan (SAP) Supporting Materials: Clinical Study Report (CSR) Supporting Materials: Analytic Code Time Frame: Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered. Access Criteria: Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). For more information on the process, or to submit a request, visit the following link. URL: https://www.abbvie.com/our-science/clinical-trials/clinical-trials-data-and-information-sharing/data-and-information-sharing-with-qualified-researchers.html
Responsible Party	AbbVie
Study Sponsor ICMJE	AbbVie
Collaborators ICMJE	Not Provided
Investigators ICMJE	Study Director: AbbVie Inc. AbbVie
PRS Account	AbbVie
Verification Date	October 2018
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP