Back to resultsA Study of Durvalumab Plus Tremelimumab With Chemotherapy in Untreated ES-SCLC
Primary Purpose
Small Cell Lung Carcinoma
Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Durvalumab + Tremelimumab in combination with carboplatin and etoposide
Durvalumab in combination with carboplatin and etoposide
Sponsored by
About this trial
This is an interventional treatment trial for Small Cell Lung Carcinoma focused on measuring Extensive stage small cell lung cancer
Eligibility Criteria
Inclusion Criteria:
- Age ≥ 18 years old at time of study entry (consent) and adult male or female (For Nebraska, ≥19 years old)
- Histologically or cytologically confirmed ES-SCLC
- Tumor biopsy or cytology should be obtained within 8 weeks of initiation of treatment.
- Brain metastases; must be asymptomatic or treated and stable, off steroids for at least 1 month prior to study treatment.
- 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.
- Measurable disease or evaluable disease based on RECIST Version 1.1.
- Eastern Cooperative Oncology Group ECOG = 2
- Body weight > 30 kg
- No active secondary malignancy. Patients with other prior malignancies will be included, provided they have been disease-free for at least five years.
- Adequate hematologic and end organ function
- Women of childbearing potential must have a pregnancy test (urine or serum) proven negative within 14 days prior to registration.
Exclusion Criteria:
- Participation in another clinical study with an investigational product during the last 28 days.
- Any previous chemotherapy and /or immunotherapy for SCLC
- Current or prior use (≤ 14 days before first doses of study drugs) of immunosuppressive medication.
- Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment.
- 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
- History of leptomeningeal carcinomatosis
- Paraneoplastic syndrome (PNS) of autoimmune nature, requiring systemic steroids or clinical symptomatology suggesting worsening of PNS
- Active infection including tuberculosis, HIV, hepatitis B and C.
- Active or prior documented autoimmune or inflammatory disorders
- Uncontrolled cardiovascular disease
- History of active primary immunodeficiency
- Pregnant or lactating women
- Known allergies, hypersensitivity, or intolerance to any of the study medications, excipients, or similar compounds.
Sites / Locations
- University of Nebraska Medical Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Cohort 1
Cohort 2
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
Incidence of Treatment-related Adverse Events with a Severity of 3 or higher (Safety and tolerability)
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.
Secondary Outcome Measures
Full Information
NCT ID
NCT03963414
First Posted
April 29, 2019
Last Updated
August 24, 2023
Sponsor
University of Nebraska
Collaborators
AstraZeneca
1. Study Identification
Unique Protocol Identification Number
NCT03963414
Brief Title
A Study of Durvalumab Plus Tremelimumab With Chemotherapy in Untreated ES-SCLC
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
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Terminated
Why Stopped
low accrual
Study Start Date
September 25, 2020 (Actual)
Primary Completion Date
December 15, 2021 (Actual)
Study Completion Date
December 15, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Nebraska
Collaborators
AstraZeneca
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This study is designed to evaluate the safety and tolerability of durvalumab and tremelimumab in combination with intravenous (IV) carboplatin plus (+) etoposide in new patients with extensive-stage small cell lung cancer (ES-SCLC).
Detailed Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Small Cell Lung Carcinoma
Keywords
Extensive stage small cell lung cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
1 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cohort 1
Arm Type
Experimental
Arm Description
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.
Arm Title
Cohort 2
Arm Type
Experimental
Arm Description
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 Type
Combination Product
Intervention Name(s)
Durvalumab + Tremelimumab in combination with carboplatin and etoposide
Other Intervention Name(s)
MEDI4736
Intervention Description
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.
Intervention Type
Combination Product
Intervention Name(s)
Durvalumab in combination with carboplatin and etoposide
Other Intervention Name(s)
MEDI4736
Intervention Description
1500mg of durvalumab in combination with carboplatin and etoposide will be given every 3 weeks for Cycles 3 and 4.
Primary Outcome Measure Information:
Title
Incidence of Treatment-related Adverse Events with a Severity of 3 or higher (Safety and tolerability)
Description
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.
Time Frame
3 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age ≥ 18 years old at time of study entry (consent) and adult male or female (For Nebraska, ≥19 years old)
Histologically or cytologically confirmed ES-SCLC
Tumor biopsy or cytology should be obtained within 8 weeks of initiation of treatment.
Brain metastases; must be asymptomatic or treated and stable, off steroids for at least 1 month prior to study treatment.
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.
Measurable disease or evaluable disease based on RECIST Version 1.1.
Eastern Cooperative Oncology Group ECOG = 2
Body weight > 30 kg
No active secondary malignancy. Patients with other prior malignancies will be included, provided they have been disease-free for at least five years.
Adequate hematologic and end organ function
Women of childbearing potential must have a pregnancy test (urine or serum) proven negative within 14 days prior to registration.
Exclusion Criteria:
Participation in another clinical study with an investigational product during the last 28 days.
Any previous chemotherapy and /or immunotherapy for SCLC
Current or prior use (≤ 14 days before first doses of study drugs) of immunosuppressive medication.
Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment.
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
History of leptomeningeal carcinomatosis
Paraneoplastic syndrome (PNS) of autoimmune nature, requiring systemic steroids or clinical symptomatology suggesting worsening of PNS
Active infection including tuberculosis, HIV, hepatitis B and C.
Active or prior documented autoimmune or inflammatory disorders
Uncontrolled cardiovascular disease
History of active primary immunodeficiency
Pregnant or lactating women
Known allergies, hypersensitivity, or intolerance to any of the study medications, excipients, or similar compounds.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Apar Ganti, MD
Organizational Affiliation
University of Nebraska
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Nebraska Medical Center
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68198
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
A Study of Durvalumab Plus Tremelimumab With Chemotherapy in Untreated ES-SCLC
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