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

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
1

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

  • United States
    • Nebraska
      • Omaha, Nebraska, United States, 68198
        • University of Nebraska Medical Center

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Nebraska

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
AstraZeneca

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • 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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 25, 2020

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 15, 2021

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 15, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 29, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 23, 2019

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 24, 2019

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 28, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 24, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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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