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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)

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ClinicalTrials.gov Identifier: NCT03061812
Recruitment Status : Completed
First Posted : February 23, 2017
Results First Posted : February 23, 2021
Last Update Posted : February 23, 2021
Sponsor:
Information provided by (Responsible Party):
AbbVie

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.

Condition or disease Intervention/treatment Phase
Small Cell Lung Cancer Drug: Rovalpituzumab tesirine Drug: Topotecan Drug: Dexamethasone Phase 3

Expanded Access : An investigational treatment associated with this study is no longer available outside the clinical trial.   More info ...

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 444 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official 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)
Actual Study Start Date : April 11, 2017
Actual Primary Completion Date : February 12, 2020
Actual Study Completion Date : February 12, 2020


Arm Intervention/treatment
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.

Drug: Rovalpituzumab tesirine
Powder for solution for infusion in vials.
Other Name: Rova-T

Drug: Dexamethasone
Oral tablet.

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.
Drug: 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.




Primary Outcome Measures :
  1. Overall Survival (OS) [ Time Frame: 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. ]
    OS is defined as the time from the date of randomization to the date of death from any cause. Participants were censored at the last date they were documented alive. After the End of treatment, survival information was collected at approximately 6-week intervals (or as requested by sponsor to support data analysis) continuing until the endpoint of death, the participant became lost to follow-up, AbbVie terminated the study, or until 12 February 2020. Calculated using the Kaplan-Meier product-limit method.


Secondary Outcome Measures :
  1. Progression Free Survival (PFS) [ Time Frame: 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. ]

    PFS is defined as the number of months from the date of randomization until the date of first progression or the date of a participant's death, whichever occurs first. If a participant neither experienced disease progression nor died, then the participant's data were censored at the last date of radiographic assessment that they were documented to be progression free. Calculated using the Kaplan-Meier product-limit method.

    Radiographic tumor assessments for response were conducted by CT scanning according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1. Progressive Disease (PD) was defined as at least a 20% increase in the size of target lesions and an absolute increase of at least 5 mm taking as reference the smallest lesion size recorded since the treatment started (baseline or after), or the appearance of one or more new lesions.


  2. 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 [ Time Frame: Baseline, Week 7 ]
    The EORTC QLQ-C15-PAL is an abbreviated 15-item version of the EORTC core quality of life questionnaire (EORTC QLQ-C30) developed for use in palliative care. The score of 'physical functioning scale' score ranges from 0 (very poor) to 100 (excellent).

  3. Objective Response Rate (ORR) [ Time Frame: 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. ]

    ORR is defined as the percentage of participants whose best overall response is either complete response (CR) or partial response (PR) according to RECIST version 1.1. Radiographic tumor assessments for response were conducted by CT scanning, and assessed from the date of randomization until disease progression or death, whichever came first. Any participant who did not meet CR or PR, including those who did not have post-baseline radiological assessments were considered non-responders.

    CR: Disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.


  4. Clinical Benefit Rate (CBR) [ Time Frame: 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. ]

    CBR is defined as percentage of participants whose best overall response is CR, PR, or stable disease (SD) according to RECIST version 1.1. Radiographic tumor assessments for response were conducted by CT scanning, and assessed from the date of randomization until disease progression or death, whichever came first. Any participant who did not meet CR, PR, or SD, including those who did not have post-baseline radiological assessments were considered as experiencing no clinical benefit.

    CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.


  5. Duration of Objective Response (DOR) [ Time Frame: 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. ]

    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. Radiographic tumor assessments for response were conducted by CT scanning, and assessed from the date of randomization until disease progression or death, whichever came first. Any participant who did not meet CR or PR, including those who did not have post-baseline radiological assessments were considered non-responders.

    CR: Disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.




Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03061812


Locations
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Sponsors and Collaborators
AbbVie
Investigators
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Study Director: AbbVie Inc. AbbVie
  Study Documents (Full-Text)

Documents provided by AbbVie:
Study Protocol  [PDF] January 8, 2019
Statistical Analysis Plan  [PDF] March 13, 2020

Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: AbbVie
ClinicalTrials.gov Identifier: NCT03061812    
Other Study ID Numbers: M16-289
2016-003726-17 ( EudraCT Number )
First Posted: February 23, 2017    Key Record Dates
Results First Posted: February 23, 2021
Last Update Posted: February 23, 2021
Last Verified: February 2021
Individual Participant Data (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
Statistical Analysis Plan (SAP)
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

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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
Keywords provided by AbbVie:
Small cell lung cancer (SCLC)
Delta-like protein 3 (DLL3)
rovalpituzumab tesirine
topotecan
metastatic
Additional relevant MeSH terms:
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Lung Neoplasms
Small Cell Lung Carcinoma
Disease Progression
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Disease Attributes
Pathologic Processes
Carcinoma, Bronchogenic
Bronchial Neoplasms
Dexamethasone
Topotecan
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action