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A Study of Durvalumab Plus Tremelimumab With Chemotherapy in Untreated ES-SCLC

Sponsor
Vinicius Ernani (Other)
Overall Status
Terminated
CT.gov ID
NCT03963414
Collaborator
AstraZeneca (Industry)
1
Enrollment
1
Location
2
Arms
18.3
Actual Duration (Months)
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This Phase I, multicenter, study is designed to evaluate the safety and tolerability of durvalumab (anti-programmed death-ligand 1 [PD-L1] antibody) and tremelimumab (anti-cytotoxic T-lymphocyte-associated protein 4 [CTLA-4] antibody) in combination with intravenous (IV) carboplatin plus (+) etoposide in treatment naïve patients with extensive-stage small cell lung cancer (ES-SCLC) and performance status 2 (PS2). Eighteen patients with untreated ES-SCLC and PS2 will be enrolled. Cohort 1, which includes the first 6 subjects, will receive IV carboplatin and etoposide Q 3 weeks x 4 cycles. Durvalumab 1500 mg IV Q 3 weeks will be given with chemotherapy during cycles 3 and 4. This will be followed by durvalumab 1500 mg IV Q 4 weeks until disease progression. If 2 out of 6 patients have dose-limiting toxicities, then the study will be closed. Cohort 2, which will include 12 additional subjects, will receive chemotherapy Q 3 weeks x 4 cycles. Durvalumab 1500 mg IV + tremelimumab 75 mg IV Q 3 weeks will be given with chemotherapy during cycles 3 and 4, then durvalumab 1500 mg + tremelimumab 75 mg will be administered Q 3 weeks during cycles 5 and 6. This will be followed by durvalumab 1500 mg IV Q 4 weeks until disease progression.

Condition or Disease Intervention/Treatment Phase
  • Combination Product: Durvalumab + Tremelimumab in combination with carboplatin and etoposide
  • Combination Product: Durvalumab in combination with carboplatin and etoposide
 Phase 1

Study Design

Study Type:
Interventional
Actual Enrollment :
1 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase I Study of Durvalumab (MEDI4736) Plus Tremelimumab in Combination With Platinum-based Chemotherapy in Untreated Extensive-Stage Small Cell Lung Cancer and Performance Status 2
Actual Study Start Date :
Jun 5, 2020
Actual Primary Completion Date :
Dec 15, 2021
Actual Study Completion Date :
Dec 15, 2021

Arms and Interventions

Arm Intervention/Treatment
Experimental: Cohort 1

Durvalumab 1500 mg via IV infusion every 3 weeks, starting on Week 7, for up to a maximum of 2 doses/cycles followed by durvalumab maintenance monotherapy 1500 mg via IV infusion every 4 weeks, starting 4 weeks after Cycle 4.

Combination Product: Durvalumab in combination with carboplatin and etoposide
1500mg of durvalumab in combination with carboplatin and etoposide will be given every 3 weeks for Cycles 3 and 4.
Other Names:
  • MEDI4736

    		•
    Experimental: Cohort 2

    Durvalumab 1500 mg plus tremelimumab 75 mg via IV infusion every 3 weeks, starting on Week 7, for up to a maximum of 2 doses/cycles followed by durvalumab monotherapy 1500 mg via IV infusion every 4 weeks, starting 4 weeks after the last infusion of the combination.

    Combination Product: Durvalumab + Tremelimumab in combination with carboplatin and etoposide
    1500mg of durvalumab plus 75mg of tremelimumab in combination with carboplatin and etoposide will be given every 3 weeks for Cycles 3 and 4. 1500mg of durvalumab plus 75mg of tremelimumab will be given every 3 weeks for Cycles 5 and 6.
    Other Names:
  • MEDI4736

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Incidence of Treatment-related Adverse Events with a Severity of 3 or higher (Safety and tolerability) [3 months]

      Evaluate the safety and tolerability profile of durvalumab + tremelimumab in combination with carboplatin and etoposide in ES-SCLC and PS2. Adverse events with a severity grade of 3 or higher per CTCAE guidelines will be used to assess this outcome.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    1. Age ≥ 18 years old at time of study entry (consent) and adult male or female (For Nebraska, ≥19 years old)

    2. Histologically or cytologically confirmed ES-SCLC

    3. Tumor biopsy or cytology should be obtained within 8 weeks of initiation of treatment.

    4. Brain metastases; must be asymptomatic or treated and stable, off steroids for at least 1 month prior to study treatment.

    5. Have not received any prior therapy for SCLC, except palliative radiation. If the patient received radiation, there must be measurable disease outside the radiation field.

    6. Measurable disease or evaluable disease based on RECIST Version 1.1.

    7. Eastern Cooperative Oncology Group ECOG = 2

    8. Body weight > 30 kg

    9. No active secondary malignancy. Patients with other prior malignancies will be included, provided they have been disease-free for at least five years.

    10. Adequate hematologic and end organ function

    11. Women of childbearing potential must have a pregnancy test (urine or serum) proven negative within 14 days prior to registration.

    Exclusion Criteria:

    1. Participation in another clinical study with an investigational product during the last 28 days.

    2. Any previous chemotherapy and /or immunotherapy for SCLC

    3. Current or prior use (≤ 14 days before first doses of study drugs) of immunosuppressive medication.

    4. Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment.

    5. History of another primary malignancy except for malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of IP

    6. History of leptomeningeal carcinomatosis

    7. Paraneoplastic syndrome (PNS) of autoimmune nature, requiring systemic steroids or clinical symptomatology suggesting worsening of PNS

    8. Active infection including tuberculosis, HIV, hepatitis B and C.

    9. Active or prior documented autoimmune or inflammatory disorders

    10. Uncontrolled cardiovascular disease

    11. History of active primary immunodeficiency

    12. Pregnant or lactating women

    13. Known allergies, hypersensitivity, or intolerance to any of the study medications, excipients, or similar compounds.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Nebraska Medical Center Omaha Nebraska United States 68198

    Sponsors and Collaborators

    • Vinicius Ernani
    • AstraZeneca

    Investigators

    • Principal Investigator: Vinicius Ernani, MD, University of Nebraska

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Vinicius Ernani, Assistant Professor of Medicine, University of Nebraska
    ClinicalTrials.gov Identifier:
    NCT03963414
    Other Study ID Numbers:
    • 275-19
    First Posted:
    May 24, 2019
    Last Update Posted:
    Mar 14, 2022
    Last Verified:
    Feb 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    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 Vinicius Ernani, Assistant Professor of Medicine, University of Nebraska
    Extensive stage small cell lung cancer
    Additional relevant MeSH terms:
    Small Cell Lung Carcinoma
    Carboplatin
    Etoposide
    Etoposide phosphate
    Durvalumab
    Tremelimumab
    Antibodies, Monoclonal

    Study Results

    No Results Posted as of Mar 14, 2022