Clinical trial NCT02819999: 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
Overall status: TERMINATED
Phase: PHASE1
Conditions: Small Cell Lung Cancer
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2016-06-30
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


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

Primary outcomes:
measure: 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)
timeFrame: within 21 days after first dose of rovalpituzumab tesirine
measure: Treatment emergent adverse events (TEAEs)
timeFrame: through 30 days after last dose of study treatment
measure: Incidence of subjects with CTCAE Grade >2 laboratory abnormalities
timeFrame: through 30 days after last dose of study treatment
measure: Progression-Free Survival (PFS)
timeFrame: 4 years
Secondary outcomes:
measure: Best overall response rate
timeFrame: 4 years
measure: Duration of response (DOR)
timeFrame: 4 years
measure: Clinical Benefit Rate (CBR)
timeFrame: 4 years
measure: Overall Survival (OS)
timeFrame: 4 years
measure: Incidence of anti-therapeutic antibodies (ATAs) against rovalpituzumab tesirine
timeFrame: 4 years
measure: Progression-free survival (Phase 1a)
timeFrame: 4 years
measure: Pharmacokinetic parameters: Cmax (Maximum plasma concentration observed )
timeFrame: 4 years
measure: Pharmacokinetic parameters: AUC0-tau (Area under the plasma concentration-time curve within a dosing interval)
timeFrame: 4 years
measure: Pharmacokinetic parameters: AUC0-∞ (Area under the curve from time 0 extrapolated to infinity)
timeFrame: 4 years
measure: Pharmacokinetic parameters: Tmax (Time of Cmax)
timeFrame: 4 years
measure: Pharmacokinetic parameters: Ctrough (Observed plasma concentrations at trough)
timeFrame: 4 years
measure: Pharmacokinetic parameters: T1/2 (Terminal half-life)
timeFrame: 4 years
measure: Pharmacokinetic parameters: CL (Clearance)
timeFrame: 4 years
measure: Pharmacokinetic parameters: Vss (Volume of distribution at steady state)
timeFrame: 4 years
measure: Incidence of TEAEs
timeFrame: 4 years
measure: Changes in vital signs (Heart Rate)
timeFrame: 4 years
measure: Changes in vital signs (Blood pressure)
timeFrame: 4 years
measure: Changes in vital signs (Temperature)
timeFrame: 4 years
measure: Changes in vital signs (Weight)
timeFrame: 4 years
measure: Changes in vital signs (Respirations)
timeFrame: 4 years
measure: Eastern Cooperative Oncology Group (ECOG) score
timeFrame: 4 years
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: Denver
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: Orlando
country: United States
facility: Cancer Institute of Florida
state: Florida
city: Baltimore
country: United States
facility: Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
state: Maryland
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Cincinnati
country: United States
facility: Oncology Hematology Care
state: Ohio
city: Cleveland
country: United States
facility: University Hospital of Cleveland
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Fort Worth
country: United States
facility: Texas Oncology
state: Texas
city: San Antonio
country: United States
facility: Texas Oncology
state: Texas
Study officials:
References: