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Trial record 2 of 18315 for:    United Therapeutics cell

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

This study is currently recruiting participants.
Verified November 2017 by United Therapeutics
Sponsor:
ClinicalTrials.gov Identifier:
NCT03098030
First Posted: March 31, 2017
Last Update Posted: November 17, 2017
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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
United Therapeutics
  Purpose
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).

Condition Intervention Phase
Small Cell Lung Cancer Biological: Dinutuximab Drug: Irinotecan Drug: Topotecan Phase 2 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by United Therapeutics:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 470
Actual Study Start Date: June 1, 2017
Estimated Study Completion Date: November 2019
Estimated Primary Completion Date: November 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Biological: Dinutuximab
Dinutuximab injection, for intravenous (IV) use
Other Names:
  • Unituxin®
  • ch14.18
Drug: Irinotecan
Irinotecan injection, IV infusion
Other Name: Camptosar®
Active Comparator: Part 2: Irinotecan
Irinotecan (350 mg/m^2 IV) on Day 1 of each q21d cycle.
Drug: Irinotecan
Irinotecan injection, IV infusion
Other Name: Camptosar®
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.
Biological: Dinutuximab
Dinutuximab injection, for intravenous (IV) use
Other Names:
  • Unituxin®
  • ch14.18
Drug: Irinotecan
Irinotecan injection, IV infusion
Other Name: Camptosar®
Active Comparator: Part 2: Topotecan
Topotecan (1.5 mg/m^2 IV) on Days 1 to 5 of each q21d cycle.
Drug: Topotecan
Topotecan for injection
Other Name: Hycamtin®

  Eligibility

Information from the National Library of Medicine

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

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 had a major surgery or significant trauma within 4 weeks of enrollment (Part 1) or randomization (Part 2).
  8. Have had organ allograft or hematopoietic transplantation.
  9. Have a history of hypersensitivity to any study drugs or their excipients, or intolerance to hydration due to preexisting pulmonary or cardiac impairment, or intolerance to opioid pain medications, or a history of severe hypersensitivity to any other antigen.
  10. Have a history or current evidence of human immunodeficiency virus (HIV) infection.
  11. Have active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection requiring treatment or have an active infection that is clinically serious in the investigator's opinion.
  12. Exposure to any investigational agent, systemic chemotherapy, or therapeutic radiation within 21 days of enrollment (Part 1) or randomization (Part 2).
  13. Exposure to strong CYP3A4 and/or UGT1A1 inhibitors and strong CYP3A4 inducers within 14 days of enrollment (Part 1) or randomization (Part 2).
  14. 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.
  Contacts and Locations
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): NCT03098030


Contacts
Contact: Odette K Jordan, MD, PMP 919-425-5606 ojordan@unither.com

  Show 217 Study Locations
Sponsors and Collaborators
United Therapeutics
  More Information

Responsible Party: United Therapeutics
ClinicalTrials.gov Identifier: NCT03098030     History of Changes
Other Study ID Numbers: DIV-SCLC-301
First Submitted: March 22, 2017
First Posted: March 31, 2017
Last Update Posted: November 17, 2017
Last Verified: November 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by United Therapeutics:
Dinutuximab
Irinotecan
Topotecan

Additional relevant MeSH terms:
Small Cell Lung Carcinoma
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Irinotecan
Camptothecin
Topotecan
Antibodies, Monoclonal
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Physiological Effects of Drugs