- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02709889
Rovalpituzumab Tesirine in Delta-Like Protein 3-Expressing Advanced Solid Tumors
September 21, 2020 updated by: AbbVie
An Open-Label Study of Rovalpituzumab Tesirine in Subjects With Delta-Like Protein 3-Expressing Advanced Solid Tumors
The primary objective of this study is to assess the safety and tolerability of rovalpituzumab tesirine in subjects with specific delta-like protein 3-expressing advanced solid tumors.
Study Overview
Status
Terminated
Conditions
Intervention / Treatment
Detailed Description
This is a multicenter, open-label study involving multiple specific advanced solid tumor types, consisting of a dose escalation part A followed by an expansion part B. Cancer subtypes will be studied in separate disease-specific cohorts in both Parts.
Eight separate cohorts will enroll malignant melanoma, medullary thyroid cancer (MTC), glioblastoma, large cell neuroendocrine carcinoma (LCNEC), neuroendocrine prostate cancer (NEPC), high-grade gastroenteropancreatic neuroendocrine carcinoma (GEP NEC), other NEC, and solid tumors other than the above.
Study Type
Interventional
Enrollment (Actual)
200
Phase
- Phase 2
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Arizona
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Gilbert, Arizona, United States, 85234
- Banner MD Anderson Cancer Ctr /ID# 155424
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Scottsdale, Arizona, United States, 85259
- Mayo Clinic - Scottsdale /ID# 155419
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California
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Los Angeles, California, United States, 90095
- University of California, Los Angeles /ID# 155429
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San Francisco, California, United States, 94143-2204
- Univ California, San Francisco /ID# 155409
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West Hollywood, California, United States, 90048
- Cedars-Sinai Medical Center - West Hollywood /ID# 155428
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Colorado
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Aurora, Colorado, United States, 80045
- Univ of Colorado Cancer Center /ID# 155415
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Denver, Colorado, United States, 80218
- Sarah Cannon Research Institute at HealthONE - Denver /ID# 155420
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Florida
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Gainesville, Florida, United States, 32610
- University of Florida - Archer /ID# 155414
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Tampa, Florida, United States, 33612-9416
- Moffitt Cancer Center /ID# 170220
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Georgia
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Atlanta, Georgia, United States, 30322
- Emory University Hospital /ID# 155417
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Kentucky
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Lexington, Kentucky, United States, 40536
- University of Kentucky Chandler Medical Center /ID# 155423
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Maryland
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Baltimore, Maryland, United States, 21287
- Johns Hopkins University /ID# 155412
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Massachusetts
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Boston, Massachusetts, United States, 02114
- Massachusetts General Hospital /ID# 155411
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Boston, Massachusetts, United States, 02215
- Dana-Farber Cancer Institute /ID# 171044
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Minnesota
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Rochester, Minnesota, United States, 55905-0001
- Mayo Clinic - Rochester /ID# 155416
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Missouri
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Saint Louis, Missouri, United States, 63110
- Washington University-School of Medicine /ID# 155425
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New Jersey
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New Brunswick, New Jersey, United States, 08903
- Rutgers Cancer Institute of NJ /ID# 162010
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New Mexico
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Albuquerque, New Mexico, United States, 87102
- University of New Mexico /ID# 205054
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New York
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Buffalo, New York, United States, 14263
- Roswell Park Comprehensive Cancer Center /ID# 162015
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New York, New York, United States, 10021
- Weill Cornell Medical College /ID# 155418
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North Carolina
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Durham, North Carolina, United States, 27710-3000
- Duke University Medical Center /ID# 155421
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Ohio
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Cleveland, Ohio, United States, 44106
- Univ Hosp Cleveland /ID# 155410
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Oregon
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Portland, Oregon, United States, 97239
- Oregon Health and Science University /ID# 162011
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South Carolina
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Greenville, South Carolina, United States, 29605
- Greenville Hospital System /ID# 155427
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Texas
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Dallas, Texas, United States, 75230
- Mary Crowley Cancer Research /ID# 162014
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Fort Worth, Texas, United States, 76104-2150
- Texas Oncology - Forth Worth /ID# 162045
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Houston, Texas, United States, 77030
- University of Texas MD Anderson Cancer Center /ID# 155413
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Utah
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Salt Lake City, Utah, United States, 84112-5500
- University of Utah /ID# 155426
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Virginia
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Fairfax, Virginia, United States, 22031
- Virginia Cancer Specialists /ID# 162006
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Washington
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Vancouver, Washington, United States, 98684
- Northwest Cancer Specialists, P.C. /ID# 155431
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 99 years (ADULT, OLDER_ADULT)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Histologically confirmed, unresectable advanced solid malignancy with documented disease progression after at least 1 prior systemic therapy
- Disease is relapsed/refractory to prior standard systemic therapy or for which standard or curative therapy does not exist or is not considered appropriate by the Investigator.
- Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
- Delta-like protein 3 (DLL3)-expressing malignancy based on central immunohistochemical (IHC) testing of representative baseline tumor tissue (archived tissue or on-study biopsy). Positive is defined as staining in ≥ 1% of tumor cells.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Minimum life expectancy of at least 12 weeks
- Subjects with a history of central nervous system (CNS) metastases must have documentation of stable or improved brain imaging for at least 2 weeks after completion of definitive treatment and within 2 weeks prior to first dose of Study Drug, off or on a stable dose of corticosteroids. Definitive treatment may include surgical resection, whole brain irradiation, and/or stereotactic radiation therapy. (Applicable to tumor types of non-CNS primary origin only)
- Recovery to Grade 1 of any clinically significant toxicity (excluding alopecia) prior to initiation of study drug administration
- Adequate hematologic and organ function as confirmed by laboratory values
Last dose of any prior therapy administered by the following time intervals before the first dose of study drug:
- Chemotherapy, small molecule inhibitors, radiation, and/or other investigational anticancer agents (excluding investigational monoclonal antibodies): 2 weeks.
- Immune-checkpoint inhibitors (e.g., anti-programmed death protein 1 [PD-1], anti-programmed death-ligand 1 [PD-L1], or anti-cytotoxic T-lymphocyte-associated protein 4 [CTLA-4]), monoclonal antibodies, antibody-drug conjugates, radioimmunoconjugates, or T-cell or other cell-based therapies: 4 weeks (2 weeks with documented disease progression).
- Females of childbearing potential must have a negative beta human chorionic gonadotropin (β-hCG) pregnancy test result within 7 days prior to the first dose of study drug. Females of non-childbearing potential are those who are postmenopausal greater than 1 year or who have had a bilateral tubal ligation or hysterectomy.
Exclusion Criteria:
- Any significant medical condition, including any suggested by screening laboratory findings that, in the opinion of the investigator or sponsor, may place the subject at undue risk from the study, including but not necessarily limited to uncontrolled hypertension and/or diabetes, clinically significant pulmonary disease (e.g., chronic obstructive pulmonary disease requiring hospitalization within 3 months) or neurological disorder (e.g., seizure disorder active within 3 months).
- 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 (NYHA) Class III-IV within 6 months prior to their first dose of study drug.
Recent or ongoing serious infection, including:
- Any active grade 3 or higher (per National Cancer Institute Common Terminology Criteria for Adverse Events version [NCI CTCAE] 4.03) viral, bacterial, or fungal infection within 2 weeks of the first dose of the study drug. Routine antimicrobial prophylaxis is permitted.
- Known seropositivity for or active infection by human immunodeficiency virus (HIV).
- Active Hepatitis B (by surface antigen expression or polymerase chain reaction) or C (by polymerase chain reaction) infection or on hepatitis-related antiviral therapy within 6 months of first dose of study drug.
- Women who are pregnant or breastfeeding
- Systemic therapy with corticosteroids at >20 mg/day prednisone or equivalent within 1 week prior to the first dose of study drug
- History of another invasive malignancy that has not been in remission for at least 3 years. Exceptions to the 3year limit include non-melanoma skin cancer, curatively treated localized prostate cancer, ductal carcinoma in situ, and cervical cancer in situ on biopsy or squamous intraepithelial lesion on pap smear.
- Prior exposure to a pyrrolobenzodiazepine (PBD)-based drug, prior participation in a rovalpituzumab tesirine clinical trial, or known hypersensitivity to rovalpituzumab tesirine or excipient contained in the drug formulation, unless undergoing retreatment with rovalpituzumab tesirine in the context of this protocol
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Rovalpituzumab Tesirine
Rovalpituzumab tesirine 0.2-0.4
mg/kg administered intravenously on Day 1 of each 6-week cycle.
Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle.
|
Other Names:
Dexamethasone will be provided through a participant's local prescription by Investigator or other provider (i.e., dexamethasone will not be provided by the Sponsor).
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Summary of Treatment-Emergent Adverse Events (TEAEs), by Dose and Neuroendocrine (NEC) or Non-NEC Disease Groups
Time Frame: From first dose of study drug through 30 days after last dose. The overall mean number of 6-week treatment cycles was 1 (range 1.0, 5.0).
|
The number of participants with TEAEs, serious TEAEs, study drug-related TEAEs, and study drug discontinuations or dose reductions due to TEAEs, summarized by dose received and neuroendocrine (NEC) or non-NEC disease groups.
An adverse event (AE) is defined as any untoward medical occurrence which does not necessarily have a causal relationship with this treatment.
A serious adverse event (SAE) is any untoward medical occurrence that at any dose: is fatal or life-threatening; results in death or hospitalization; is disabling/incapacitating or a congenital anomaly/birth defect; is medically significant.
AE severity was graded using the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.03 terminology: grade 1=mild; grade 2=moderate; grade 3=severe; grade 4 life-threatening; grade 5=death.
TEAEs were defined as AEs that were newly occurring or worsened following study treatment.
|
From first dose of study drug through 30 days after last dose. The overall mean number of 6-week treatment cycles was 1 (range 1.0, 5.0).
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Objective Response Rate (ORR)
Time Frame: Baseline, every 6 weeks until 6 months, then every 12 weeks until disease progression, assessed up to 35.2 months.
|
ORR is defined as percentage of participants whose best overall response was either complete response (CR) or partial response (PR), according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
CR: Disappearance of all target lesions.
Any pathological lymph nodes must have reduction in short axis to <10 mm.
PR: A ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
|
Baseline, every 6 weeks until 6 months, then every 12 weeks until disease progression, assessed up to 35.2 months.
|
Clinical Benefit Rate (CBR)
Time Frame: Baseline, every 6 weeks until 6 months, then every 12 weeks until disease progression, assessed up to 35.2 months.
|
CBR is defined as the percentage of participants with best overall response (confirmed or unconfirmed) of CR, PR or stable disease (SD) per RECIST v1.1.
CR: Disappearance of all target lesions.
Any pathological lymph nodes must have reduction in short axis to <10 mm.
PR: 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 progressed disease (PD), taking as reference the smallest sum diameters while on study.
SD criteria must have met at least once after study entry at a minimum interval of 42 days (-7 days to allow for scheduled visit window per the protocol).
|
Baseline, every 6 weeks until 6 months, then every 12 weeks until disease progression, assessed up to 35.2 months.
|
Duration of Response (DOR)
Time Frame: Baseline, every 6 weeks until 6 months, then every 12 weeks until disease progression, assessed up to 35.2 months.
|
DOR is defined as the time from the first assessment on therapy of a CR or PR response (per RECIST v1.1) to the date of progressive disease or death.
CR: Disappearance of all target lesions.
Any pathological lymph nodes must have reduction in short axis to <10 mm.
PR: A ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Participants who did not have progression were censored at the last non-missing response assessment on-therapy or baseline.
Based on Kaplan-Meier estimates.
|
Baseline, every 6 weeks until 6 months, then every 12 weeks until disease progression, assessed up to 35.2 months.
|
Progression Free Survival (PFS)
Time Frame: Baseline, every 6 weeks until 6 months, then every 12 weeks until disease progression, assessed up to 35.2 months.
|
PFS is defined as the time from the first dose date to the date of disease progression or death.
Participants who did not have progression or death are censored at the last non-missing response assessment on-therapy or baseline.
Based on Kaplan-Meier estimates.
|
Baseline, every 6 weeks until 6 months, then every 12 weeks until disease progression, assessed up to 35.2 months.
|
Overall Survival (OS)
Time Frame: Baseline, every 6 weeks until 6 months, then every 12 weeks until disease progression, assessed up to 35.2 months.
|
Overall survival is defined as the time from the first dose date to death for any reason.
Subjects who were alive at the clinical data cut-off are censored at the last known alive date.
Based on Kaplan-Meier estimates.
|
Baseline, every 6 weeks until 6 months, then every 12 weeks until disease progression, assessed up to 35.2 months.
|
Serum Concentrations of Rovalpituzumab Tesirine Over Time
Time Frame: Cycle 1: 0, 0.5, 6, 48, 168, 336, 672 hours postdose
|
Cycle 1: 0, 0.5, 6, 48, 168, 336, 672 hours postdose
|
|
Number of Participants With Anti-therapeutic Antibodies (ATA)
Time Frame: Day 1 and 42 days after last dose. The overall mean number of 6-week treatment cycles was 1 (range 1.0, 5.0).
|
Number of participants treated across each dose level reported to potentially have ATAs against rovalpituzumab tesirine at any time during the study.
|
Day 1 and 42 days after last dose. The overall mean number of 6-week treatment cycles was 1 (range 1.0, 5.0).
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (ACTUAL)
September 23, 2016
Primary Completion (ACTUAL)
August 27, 2019
Study Completion (ACTUAL)
August 27, 2019
Study Registration Dates
First Submitted
March 2, 2016
First Submitted That Met QC Criteria
March 10, 2016
First Posted (ESTIMATE)
March 16, 2016
Study Record Updates
Last Update Posted (ACTUAL)
October 19, 2020
Last Update Submitted That Met QC Criteria
September 21, 2020
Last Verified
September 1, 2020
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Adenocarcinoma
- Neoplasms, Glandular and Epithelial
- Astrocytoma
- Glioma
- Neoplasms, Neuroepithelial
- Neuroectodermal Tumors
- Neoplasms, Germ Cell and Embryonal
- Neoplasms, Nerve Tissue
- Neuroendocrine Tumors
- Nevi and Melanomas
- Carcinoma
- Glioblastoma
- Melanoma
- Carcinoma, Neuroendocrine
- Physiological Effects of Drugs
- Autonomic Agents
- Peripheral Nervous System Agents
- Anti-Inflammatory Agents
- Antineoplastic Agents
- Antiemetics
- Gastrointestinal Agents
- Glucocorticoids
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Dexamethasone
Other Study ID Numbers
- SCRX001-006
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
YES
IPD 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.
IPD Sharing Time Frame
Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered.
IPD Sharing 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.
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- SAP
- CSR
Drug and device information, study documents
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
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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