A Study of Rovalpituzumab Tesirine (SC16LD6.5) in the Frontline Treatment of Patients With Extensive Stage Small Cell Lung Cancer
Primary Purpose
Small Cell Lung Cancer
Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Rovalpituzumab Tesirine
Cisplatin
Etoposide
Sponsored by
About this trial
This is an interventional treatment trial for Small Cell Lung Cancer
Eligibility Criteria
Inclusion Criteria:
- Age ≥ 18 years with histologically- or cytologically-confirmed, extensive-stage, chemotherapy-naïve SCLC
- DLL3-expressing SCLC based on central immunohistochemistry (IHC) assessment. Positive is defined as staining in ≥75% of tumor cells.
- Eastern Cooperative Oncology Group performance status of 0 or 1.
- Minimum life expectancy of at least 12 weeks.
- Recovery to Grade 1 of any clinically significant toxicity (excluding alopecia) prior to initiation of study drug.
- Satisfactory laboratory parameters within defined parameters (ANC, platelet count, Hb, total bilirubin, ALT, AST and GFR)
- Subjects with a history of CNS metastases must have completed definitive treatment prior to first dose of study treatment, off or on a stable dose of corticosteroids
- Use of effective contraception method during and for 1 year following study drug dosing if female of childbearing potential or sexually active male
Exclusion Criteria:
- Prior systemic chemotherapy, small molecule inhibitors, immune checkpoint inhibitors, other monoclonal antibodies, antibody-drug conjugates, radioimmunoconjugates, T-cell or other cell-based or biologic therapies, or any other anticancer therapy for the treatment of (limited or extensive) SCLC.
- Any significant medical condition, that, in the opinion of the investigator or sponsor, may place the subject at undue risk from the study.
- Documented history of a cerebral vascular, 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.
- Women who are pregnant or breastfeeding.
- History of another invasive malignancy that has not been in remission for at least 3 years. Exceptions: nonmelanoma skin cancer, curatively treated localized prostate cancer, and cervical cancer in situ on biopsy or squamous intraepithelial lesion on PAP smear.
- Prior exposure to a pyrrolobenzodiazepine (PBD)-based drug, or known hypersensitivity to rovalpituzumab tesirine or excipient contained in the drug formulation
Sites / Locations
- University of Colorado
- Rocky Mountain Cancer Centers
- Cancer Institute of Florida
- Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
- Washington University
- Oncology Hematology Care
- University Hospital of Cleveland
- Cleveland Clinic
- University of Pittsburgh
- Texas Oncology
- Texas Oncology
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
Rovalpituzumab Tesirine
Rovalpituzumab Tesirine followed by Cisplatin, Etoposide
Rovalpituzumab Tesirine with Cisplatin, Etoposide
Rovalpituzumab Tesirine following Cisplatin, Etoposide
Arm Description
Rovalpituzumab Tesirine 0.3 mg/kg IV infusion
Rovalpituzumab Tesirine 0.3 mg/kg IV infusion followed by Cisplatin 80 mg/m2 and Etoposide 100 mg/m2 IV infusion
Cisplatin 80 mg/m2 and Etoposide 100 mg/m2 IV infusion and Rovalpituzumab Tesirine 0.1 mg/kg IV infusion
Cisplatin 80 mg/m2 and Etoposide 100 mg/m2 IV infusion followed by Rovalpituzumab Tesirine 0.3 mg/kg IV infusion
Outcomes
Primary Outcome Measures
Dose limiting toxicities (DLT) of rovalpituzumab tesirine when administered as monotherapy, in series or in combination with frontline chemotherapy to subjects with DLL3 expressing extensive-stage small cell lung cancer (SCLC)
For Phase 1a
Treatment emergent adverse events (TEAEs)
For Phase 1a
Incidence of subjects with CTCAE Grade >2 laboratory abnormalities
For Phase 1a
Progression-Free Survival (PFS)
For Phase 1b
Secondary Outcome Measures
Best overall response rate
Duration of response (DOR)
Clinical Benefit Rate (CBR)
Overall Survival (OS)
Incidence of anti-therapeutic antibodies (ATAs) against rovalpituzumab tesirine
Progression-free survival (Phase 1a)
Pharmacokinetic parameters: Cmax (Maximum plasma concentration observed )
Pharmacokinetic parameters: AUC0-tau (Area under the plasma concentration-time curve within a dosing interval)
Pharmacokinetic parameters: AUC0-∞ (Area under the curve from time 0 extrapolated to infinity)
Pharmacokinetic parameters: Tmax (Time of Cmax)
Pharmacokinetic parameters: Ctrough (Observed plasma concentrations at trough)
Pharmacokinetic parameters: T1/2 (Terminal half-life)
Pharmacokinetic parameters: CL (Clearance)
Pharmacokinetic parameters: Vss (Volume of distribution at steady state)
Incidence of TEAEs
For Phase 1b
Changes in vital signs (Heart Rate)
Changes in vital signs (Blood pressure)
Changes in vital signs (Temperature)
Changes in vital signs (Weight)
Changes in vital signs (Respirations)
Eastern Cooperative Oncology Group (ECOG) score
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02819999
Brief Title
A Study of Rovalpituzumab Tesirine (SC16LD6.5) in the Frontline Treatment of Patients With Extensive Stage Small Cell Lung Cancer
Official Title
A Study of Rovalpituzumab Tesirine (SC16LD6.5) in the Frontline Treatment of Patients With Extensive Stage Small Cell Lung Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
June 2019
Overall Recruitment Status
Terminated
Why Stopped
Strategic considerations
Study Start Date
October 2016 (undefined)
Primary Completion Date
May 31, 2019 (Actual)
Study Completion Date
May 31, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AbbVie
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of the study is to test the effect of rovalpituzumab tesirine in the frontline treatment of small cell lung cancer (SCLC).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Small Cell Lung Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
28 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Rovalpituzumab Tesirine
Arm Type
Experimental
Arm Description
Rovalpituzumab Tesirine 0.3 mg/kg IV infusion
Arm Title
Rovalpituzumab Tesirine followed by Cisplatin, Etoposide
Arm Type
Experimental
Arm Description
Rovalpituzumab Tesirine 0.3 mg/kg IV infusion followed by Cisplatin 80 mg/m2 and Etoposide 100 mg/m2 IV infusion
Arm Title
Rovalpituzumab Tesirine with Cisplatin, Etoposide
Arm Type
Experimental
Arm Description
Cisplatin 80 mg/m2 and Etoposide 100 mg/m2 IV infusion and Rovalpituzumab Tesirine 0.1 mg/kg IV infusion
Arm Title
Rovalpituzumab Tesirine following Cisplatin, Etoposide
Arm Type
Experimental
Arm Description
Cisplatin 80 mg/m2 and Etoposide 100 mg/m2 IV infusion followed by Rovalpituzumab Tesirine 0.3 mg/kg IV infusion
Intervention Type
Drug
Intervention Name(s)
Rovalpituzumab Tesirine
Other Intervention Name(s)
SC16LD6.5
Intervention Description
Rovalpituzumab tesirine is a DLL3 targeted antibody drug conjugate (ADC).
Intervention Type
Drug
Intervention Name(s)
Cisplatin
Intervention Type
Drug
Intervention Name(s)
Etoposide
Primary Outcome Measure Information:
Title
Dose limiting toxicities (DLT) of rovalpituzumab tesirine when administered as monotherapy, in series or in combination with frontline chemotherapy to subjects with DLL3 expressing extensive-stage small cell lung cancer (SCLC)
Description
For Phase 1a
Time Frame
within 21 days after first dose of rovalpituzumab tesirine
Title
Treatment emergent adverse events (TEAEs)
Description
For Phase 1a
Time Frame
through 30 days after last dose of study treatment
Title
Incidence of subjects with CTCAE Grade >2 laboratory abnormalities
Description
For Phase 1a
Time Frame
through 30 days after last dose of study treatment
Title
Progression-Free Survival (PFS)
Description
For Phase 1b
Time Frame
4 years
Secondary Outcome Measure Information:
Title
Best overall response rate
Time Frame
4 years
Title
Duration of response (DOR)
Time Frame
4 years
Title
Clinical Benefit Rate (CBR)
Time Frame
4 years
Title
Overall Survival (OS)
Time Frame
4 years
Title
Incidence of anti-therapeutic antibodies (ATAs) against rovalpituzumab tesirine
Time Frame
4 years
Title
Progression-free survival (Phase 1a)
Time Frame
4 years
Title
Pharmacokinetic parameters: Cmax (Maximum plasma concentration observed )
Time Frame
4 years
Title
Pharmacokinetic parameters: AUC0-tau (Area under the plasma concentration-time curve within a dosing interval)
Time Frame
4 years
Title
Pharmacokinetic parameters: AUC0-∞ (Area under the curve from time 0 extrapolated to infinity)
Time Frame
4 years
Title
Pharmacokinetic parameters: Tmax (Time of Cmax)
Time Frame
4 years
Title
Pharmacokinetic parameters: Ctrough (Observed plasma concentrations at trough)
Time Frame
4 years
Title
Pharmacokinetic parameters: T1/2 (Terminal half-life)
Time Frame
4 years
Title
Pharmacokinetic parameters: CL (Clearance)
Time Frame
4 years
Title
Pharmacokinetic parameters: Vss (Volume of distribution at steady state)
Time Frame
4 years
Title
Incidence of TEAEs
Description
For Phase 1b
Time Frame
4 years
Title
Changes in vital signs (Heart Rate)
Time Frame
4 years
Title
Changes in vital signs (Blood pressure)
Time Frame
4 years
Title
Changes in vital signs (Temperature)
Time Frame
4 years
Title
Changes in vital signs (Weight)
Time Frame
4 years
Title
Changes in vital signs (Respirations)
Time Frame
4 years
Title
Eastern Cooperative Oncology Group (ECOG) score
Time Frame
4 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age ≥ 18 years with histologically- or cytologically-confirmed, extensive-stage, chemotherapy-naïve SCLC
DLL3-expressing SCLC based on central immunohistochemistry (IHC) assessment. Positive is defined as staining in ≥75% of tumor cells.
Eastern Cooperative Oncology Group performance status of 0 or 1.
Minimum life expectancy of at least 12 weeks.
Recovery to Grade 1 of any clinically significant toxicity (excluding alopecia) prior to initiation of study drug.
Satisfactory laboratory parameters within defined parameters (ANC, platelet count, Hb, total bilirubin, ALT, AST and GFR)
Subjects with a history of CNS metastases must have completed definitive treatment prior to first dose of study treatment, off or on a stable dose of corticosteroids
Use of effective contraception method during and for 1 year following study drug dosing if female of childbearing potential or sexually active male
Exclusion Criteria:
Prior systemic chemotherapy, small molecule inhibitors, immune checkpoint inhibitors, other monoclonal antibodies, antibody-drug conjugates, radioimmunoconjugates, T-cell or other cell-based or biologic therapies, or any other anticancer therapy for the treatment of (limited or extensive) SCLC.
Any significant medical condition, that, in the opinion of the investigator or sponsor, may place the subject at undue risk from the study.
Documented history of a cerebral vascular, 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.
Women who are pregnant or breastfeeding.
History of another invasive malignancy that has not been in remission for at least 3 years. Exceptions: nonmelanoma skin cancer, curatively treated localized prostate cancer, and cervical cancer in situ on biopsy or squamous intraepithelial lesion on PAP smear.
Prior exposure to a pyrrolobenzodiazepine (PBD)-based drug, or known hypersensitivity to rovalpituzumab tesirine or excipient contained in the drug formulation
Facility Information:
Facility Name
University of Colorado
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80010
Country
United States
Facility Name
Rocky Mountain Cancer Centers
City
Denver
State/Province
Colorado
ZIP/Postal Code
80218
Country
United States
Facility Name
Cancer Institute of Florida
City
Orlando
State/Province
Florida
ZIP/Postal Code
32804
Country
United States
Facility Name
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21231
Country
United States
Facility Name
Washington University
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Oncology Hematology Care
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45242
Country
United States
Facility Name
University Hospital of Cleveland
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
University of Pittsburgh
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15232
Country
United States
Facility Name
Texas Oncology
City
Fort Worth
State/Province
Texas
ZIP/Postal Code
76104
Country
United States
Facility Name
Texas Oncology
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78258
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
A Study of Rovalpituzumab Tesirine (SC16LD6.5) in the Frontline Treatment of Patients With Extensive Stage Small Cell Lung Cancer
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