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出境医 / 临床实验 / A Study of Durvalumab Plus Tremelimumab With Chemotherapy in Untreated ES-SCLC

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

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
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

Study Design
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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
Actual Study Start Date : June 5, 2020
Estimated Primary Completion Date : December 1, 2021
Estimated Study Completion Date : December 1, 2022
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 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
Outcome Measures
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.


Eligibility Criteria
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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.
Contacts and Locations

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 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
Tracking Information
First Submitted Date  ICMJE April 29, 2019
First Posted Date  ICMJE May 24, 2019
Last Update Posted Date July 17, 2020
Actual Study Start Date  ICMJE June 5, 2020
Estimated Primary Completion Date December 1, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 23, 2019) 		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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Durvalumab Plus Tremelimumab With Chemotherapy in Untreated ES-SCLC
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Small Cell Lung Carcinoma
Intervention  ICMJE
  • 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
  • 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
Study Arms  ICMJE
  • 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.
    Intervention: Combination Product: Durvalumab in combination with carboplatin and etoposide
  • 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.
    Intervention: Combination Product: Durvalumab + Tremelimumab in combination with carboplatin and etoposide
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 Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 23, 2019) 		18
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 1, 2022
Estimated Primary Completion Date December 1, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
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: April Winchester 402-559-0963 april.winchester@unmc.edu
Contact: Peggy Heires 402-559-4596 peggy.heires@unmc.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03963414
Other Study ID Numbers  ICMJE 275-19
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 Vinicius Ernani, University of Nebraska
Study Sponsor  ICMJE Vinicius Ernani
Collaborators  ICMJE AstraZeneca
Investigators  ICMJE
Principal Investigator: Vinicius Ernani, MD University of Nebraska
PRS Account University of Nebraska
Verification Date July 2020

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

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