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Dinutuximab and Irinotecan Versus Irinotecan to Treat Subjects With Relapsed or Refractory Small Cell Lung Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03098030
Recruitment Status : Completed
First Posted : March 31, 2017
Last Update Posted : April 29, 2020
Sponsor:
Information provided by (Responsible Party):
United Therapeutics

Tracking Information
First Submitted Date  ICMJE March 22, 2017
First Posted Date  ICMJE March 31, 2017
Last Update Posted Date April 29, 2020
Actual Study Start Date  ICMJE June 1, 2017
Actual Primary Completion Date January 27, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 27, 2017)
Overall survival (OS) [ Time Frame: Up to approximately 2.5 years ]
OS will be derived as: (date of death - date of randomization) + 1. Subjects who are alive or permanently lost to follow-up at the cut-off date for the analysis will be censored at the last date the subject was known to be alive.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 27, 2017)
  • Progression-free survival (PFS) [ Time Frame: Up to approximately 2.5 years ]
    PFS will be defined as the time from the date of randomization to the date of first documentation of tumor progression or death from any cause, whichever occurs first.
  • Objective response rate (ORR) [ Time Frame: Up to approximately 2.5 years ]
    The ORR is the percentage of subjects with best overall response of either complete response (CR) or partial response (PR).
  • Clinical benefit rate (CBR) [ Time Frame: Up to approximately 2.5 years ]
    The CBR is defined as the proportion of subjects with either a CR, PR, or stable disease (SD), relative to the number of subjects in the treatment group.
  • Area under the concentration versus time curve (AUC) of dinutuximab [ Time Frame: Approximately 4 months ]
    The area under the plot of plasma concentration of dinutuximab against time after administration
  • Maximum concentration (Cmax) of dinutuximab [ Time Frame: Approximately 4 months ]
    Cmax is a measure of the highest concentration of dinutuximab in the blood that is measured after a dose.
  • Halt-life (t1/2) of dinutuximab [ Time Frame: Approximately 4 months ]
    The half-life represents the time it takes for the dinutuximab concentration in the body to be reduced by 50%.
  • Clearance (CL) of dinutuximab [ Time Frame: Approximately 4 months ]
    Clearance is a measure of the body's efficiency in eliminating dinutuximab.
  • Incidence of adverse events [ Time Frame: Up to approximately 2.5 years ]
    The incidence of adverse events among subjects throughout the study will be measured by the number of subjects analyzed and the percentage of subjects who experienced an adverse event.
  • Incidence of toxicities [ Time Frame: Up to approximately 2.5 years ]
    The incidence of toxicities will be determined by the percentage of subjects who experienced a laboratory abnormality, among all subjects exposed to each treatment.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Dinutuximab and Irinotecan Versus Irinotecan to Treat Subjects With Relapsed or Refractory Small Cell Lung Cancer
Official Title  ICMJE A Two-part, Open-label, Randomized, Phase 2/3 Study of Dinutuximab and Irinotecan Versus Irinotecan for Second Line Treatment of Subjects With Relapsed or Refractory Small Cell Lung Cancer
Brief Summary This is a 2-part, multicenter, open-label, randomized study of dinutuximab and irinotecan versus irinotecan alone in subjects with relapsed or refractory small cell lung cancer (SCLC). Part 1 of the study involves intrasubject dose escalation to evaluate the safety and tolerability of dinutuximab in combination with irinotecan. Part 2 of the study is designed to determine whether dinutuximab plus irinotecan prolongs overall survival (OS) compared with irinotecan alone. Subjects in Part 2 will be randomized in a 2:2:1 fashion to 1 of 3 treatment groups: (A) irinotecan; (B) dinutuximab plus irinotecan; or (C) topotecan. Randomization will be stratified by duration of response to prior platinum therapy (relapse-free period <3 months or ≥3 months).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
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
  • Biological: Dinutuximab
    Dinutuximab injection, for intravenous (IV) use
    Other Names:
    • Unituxin®
    • ch14.18
  • Drug: Irinotecan
    Irinotecan injection, IV infusion
    Other Name: Camptosar®
  • Drug: Topotecan
    Topotecan for injection
    Other Name: Hycamtin®
Study Arms  ICMJE
  • Experimental: Part 1: Dinutuximab + Irinotecan
    Dinutuximab (10 mg/m^2 IV) + Irinotecan (350 mg/m^2 IV) on Day 1 of every 21 days (q21d). Dinutuximab dose will be escalated in 2 mg/m^2 increments per cycle if maximal pain is <Grade 2 (and without opioids) and otherwise tolerated, up to a maximum dose of 17.5 mg/m^2 IV.
    Interventions:
    • Biological: Dinutuximab
    • Drug: Irinotecan
  • Active Comparator: Part 2: Irinotecan
    Irinotecan (350 mg/m^2 IV) on Day 1 of each q21d cycle.
    Intervention: Drug: Irinotecan
  • Experimental: Part 2: Dinutuximab + Irinotecan
    Dinutuximab (10 mg/m^2 IV) + Irinotecan (350 mg/m^2 IV) on Day 1 of each q21d cycle. Dinutuximab dose will be escalated in 2 mg/m^2 increments per cycle if maximal pain is <Grade 2 (and without opioids) and otherwise tolerated, up to a maximum dose of 17.5 mg/m^2 IV.
    Interventions:
    • Biological: Dinutuximab
    • Drug: Irinotecan
  • Active Comparator: Part 2: Topotecan
    Topotecan (1.5 mg/m^2 IV) on Days 1 to 5 of each q21d cycle.
    Intervention: Drug: Topotecan
Publications * Not Provided

*   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 Completed
Actual Enrollment  ICMJE
 (submitted: November 2, 2018)
485
Original Estimated Enrollment  ICMJE
 (submitted: March 27, 2017)
470
Actual Study Completion Date  ICMJE March 26, 2020
Actual Primary Completion Date January 27, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Have histologically or cytologically confirmed SCLC (undifferentiated small-cell carcinoma arising in or consistent with lung cancer origin).
  2. Documented relapse or disease progression during or after first-line platinum-based therapy (subjects refractory to initial platinum-based therapy are eligible).
  3. Have no curative therapy available.
  4. Have a life expectancy of at least 12 weeks.
  5. Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  6. Have adequate bone marrow and hepatic function.
  7. Have calculated creatinine clearance (CrCL) ≥30 mL/minute or serum creatinine ≤1.5 times below the upper limit of normal.
  8. Women of reproductive potential must not be pregnant or breastfeeding and have a negative urine or serum pregnancy test obtained within 7 days prior to the first dose of study treatment.
  9. Subjects must agree to consistently use 2 forms of highly effective contraception/birth control between signing of the informed consent and 60 days after the last study drug administration.

Exclusion Criteria:

  1. Candidate for re-treatment with original platinum-based regimen as second-line therapy.
  2. Prior treatment with irinotecan, topotecan, or dinutuximab.
  3. Have active brain metastases. Subjects with brain metastases are allowed if they completed definitive brain therapy, are asymptomatic and radiologically stable, and if they are not currently receiving corticosteroids or radiation.
  4. Have mixed small cell and non-small cell histologic features.
  5. Have a previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study, except cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors (Ta and Tis [carcinoma in situ]) or any previous cancer curatively treated <3 years ago.
  6. Have a history or current evidence of uncontrolled cardiovascular disease.
  7. Have not recovered from prior surgery, significant trauma, systemic anticancer therapy, radiation therapy or investigational therapy to Grade 1 or better toxicity prior to enrollment (Part 1) or randomization (Part 2).
  8. Have had organ allograft or hematopoietic transplantation.
  9. Known to be human immunodeficiency virus (HIV) positive.
  10. Have an active infection requiring treatment or one that is clinically serious in the Investigator's opinion.
  11. Have received a live vaccine within 6 months of enrollment (Part 1) or randomization (Part 2).
  12. Exposure to strong CYP3A4 and/or UGT1A1 inhibitors and strong CYP3A4 inducers within 14 days of enrollment (Part 1) or randomization (Part 2).
  13. Have any clinical condition that is considered unstable or might jeopardize the safety of the subject and/or influence the subject's compliance in the study.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Bulgaria,   Canada,   France,   Georgia,   Hong Kong,   Hungary,   India,   Italy,   Korea, Republic of,   Lithuania,   Malaysia,   Philippines,   Poland,   Romania,   Russian Federation,   Slovakia,   Spain,   Taiwan,   Thailand,   Ukraine,   United Kingdom,   United States
Removed Location Countries Germany
 
Administrative Information
NCT Number  ICMJE NCT03098030
Other Study ID Numbers  ICMJE DIV-SCLC-301
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party United Therapeutics
Study Sponsor  ICMJE United Therapeutics
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account United Therapeutics
Verification Date April 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP