- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03963414
A Study of Durvalumab Plus Tremelimumab With Chemotherapy in Untreated ES-SCLC
August 24, 2023 updated by: University of Nebraska
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
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).
Study Overview
Status
Terminated
Conditions
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.
Study Type
Interventional
Enrollment (Actual)
1
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
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Nebraska
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Omaha, Nebraska, United States, 68198
- University of Nebraska Medical Center
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / 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.
|
1500mg of durvalumab in combination with carboplatin and etoposide will be given every 3 weeks for Cycles 3 and 4.
Other Names:
|
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.
|
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:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
3 months
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Principal Investigator: Apar Ganti, MD, University of Nebraska
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
September 25, 2020
Primary Completion (Actual)
December 15, 2021
Study Completion (Actual)
December 15, 2021
Study Registration Dates
First Submitted
April 29, 2019
First Submitted That Met QC Criteria
May 23, 2019
First Posted (Actual)
May 24, 2019
Study Record Updates
Last Update Posted (Actual)
August 28, 2023
Last Update Submitted That Met QC Criteria
August 24, 2023
Last Verified
August 1, 2023
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Respiratory Tract Diseases
- Neoplasms
- Lung Diseases
- Neoplasms by Site
- Respiratory Tract Neoplasms
- Thoracic Neoplasms
- Carcinoma, Bronchogenic
- Bronchial Neoplasms
- Lung Neoplasms
- Small Cell Lung Carcinoma
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Immunologic Factors
- Antineoplastic Agents, Phytogenic
- Topoisomerase II Inhibitors
- Topoisomerase Inhibitors
- Antineoplastic Agents, Immunological
- Carboplatin
- Etoposide
- Etoposide phosphate
- Durvalumab
- Tremelimumab
- Antibodies, Monoclonal
Other Study ID Numbers
- 0275-19-FB
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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