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

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ClinicalTrials.gov Identifier: NCT03963414
Recruitment Status : Not yet recruiting
First Posted : May 24, 2019
Last Update Posted : May 24, 2019
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
Vinicius Ernani, University of Nebraska

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
Small Cell Lung Carcinoma Combination Product: Durvalumab + Tremelimumab in combination with carboplatin and etoposide Combination Product: Durvalumab in combination with carboplatin and etoposide Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 18 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
Estimated Study Start Date : July 1, 2019
Estimated Primary Completion Date : July 1, 2021
Estimated Study Completion Date : July 1, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

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 Name: 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 Name: MEDI4736




Primary Outcome Measures :
  1. Incidence of Treatment-related Adverse Events with a Severity of 3 or higher (Safety and tolerability) [ Time Frame: 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.



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

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.

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): NCT03963414


Contacts
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Contact: April Winchester 402-559-0963 april.winchester@unmc.edu
Contact: Peggy Heires 402-559-4596 peggy.heires@unmc.edu

Locations
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United States, Nebraska
University of Nebraska Medical Center Not yet recruiting
Omaha, Nebraska, United States, 68198
Sponsors and Collaborators
Vinicius Ernani
AstraZeneca
Investigators
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Principal Investigator: Vinicius Ernani, MD University of Nebraska

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Responsible Party: Vinicius Ernani, Assistant Professor of Medicine, University of Nebraska
ClinicalTrials.gov Identifier: NCT03963414     History of Changes
Other Study ID Numbers: 275-19
First Posted: May 24, 2019    Key Record Dates
Last Update Posted: May 24, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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

Keywords provided by Vinicius Ernani, University of Nebraska:
Extensive stage small cell lung cancer

Additional relevant MeSH terms:
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Small Cell Lung Carcinoma
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carboplatin
Etoposide
Etoposide phosphate
Durvalumab
Tremelimumab
Antibodies, Monoclonal
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological
Immunologic Factors
Physiological Effects of Drugs