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Subsequent Line Gemcitabine and Nivolumab in Treating Participants With Metastatic Small Cell Lung Cancer

Primary Purpose

Small Cell Lung Carcinoma, Stage IV Lung Cancer AJCC v8, Stage IVA Lung Cancer AJCC v8

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Gemcitabine
Nivolumab
Sponsored by
Wake Forest University Health Sciences
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Small Cell Lung Carcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients must have histologically or cytologically confirmed incurable SCLC and have had prior treatment with platinum-based chemotherapy. High-grade neuroendocrine tumors that are suspected to be of bronchopulmonary origin can be enrolled if they have had prior treatment with a SCLC chemotherapy regimen (e.g. platinum plus etoposide).
  • Patients should not be demonstrating end-organ damage due to rapid progression of disease based on the most recent assessment of the treating physician.
  • Patients must have radiographically measurable metastatic disease by Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
  • Absolute neutrophil count >= 1,500/mcL.
  • Platelets >= 100,000/mcL.
  • Chemotherapy agents are known to be teratogenic, therefore women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
  • Ability to understand and the willingness to sign an Institutional Review Board (IRB)-approved informed consent document.

Exclusion Criteria:

  • Patients who have previously received either gemcitabine or an immune checkpoint inhibitor can be enrolled.
  • Emergent need for palliative radiation.
  • Patients may not be receiving any other investigational agents for the treatment of nonsmall cell lung cancer.
  • History of allergic reaction to gemcitabine.
  • Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Pregnant women are excluded from this study because of the potential for teratogenic or abortifacient effects with chemotherapy. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with chemotherapy, breastfeeding should be discontinued.

Sites / Locations

  • Wake Forest University Health Sciences

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (gemcitabine, nivolumab)

Arm Description

Participants receive gemcitabine IV over 30 minutes and nivolumab IV over 60 minutes on day 1. Treatment repeats every 2 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity

Outcomes

Primary Outcome Measures

Number of Participants With Positive Responses to Therapy Per Response Evaluation Criteria in Solid Tumors (RECIST)
Objective RR (complete response [CR] + partial response [PR]) will be compared between this study sample and a historical benchmark value of 10%. For this comparison we will use a one-sample test of proportion. Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): Decrease by ≥ 30% in sum of longest diameter of target lesions. Stable Disease (SD): Not meeting criteria for CR, PR, or PD. Progressive Disease (PD): Increase by ≥ 20% in sum of longest diameter of target lesions or the appearance of one or more new lesions. The response in non-target lesions is defined as follows: Complete Response (CR): Complete disappearance of all non-target lesions. Stable Disease (SD): Persistence of one or more non-target lesion(s). Progressive Disease (PD): Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.

Secondary Outcome Measures

Overall Survival (OS) - Number of Participants
OS will be estimated using standard Kaplan Meier survival analysis methods.
Overall Survival (OS) - Months
A median value (months) of overall survival will be estimated using standard Kaplan Meier survival analysis methods.
Progression-free Survival (PFS) - Number of Participants
Progression-free survival will be estimated using standard Kaplan Meier survival analysis methods. Progression-Free Survival (PFS) is defined as the duration of time from the start of treatment to the time of investigator assessed progression or death. Progressive Disease (PD): Increase by ≥ 20% in sum of longest diameter of target lesions or the appearance of one or more new lesions
Progression-free Survival (PFS) - Months
A median value (months) of progressive-free survival will be estimated using standard Kaplan Meier survival analysis methods. Progressive Disease (PD): Increase by ≥ 20% in sum of longest diameter of target lesions or the appearance of one or more new lesions
Number of Adverse Events
Toxicity rates will be estimated by responder status and presented overall and by body site per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0

Full Information

First Posted
September 5, 2018
Last Updated
July 26, 2023
Sponsor
Wake Forest University Health Sciences
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT03662074
Brief Title
Subsequent Line Gemcitabine and Nivolumab in Treating Participants With Metastatic Small Cell Lung Cancer
Official Title
Phase II Pilot Study of Subsequent Line Gemcitabine and Nivolumab for Advanced SCLC
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Terminated
Why Stopped
After interim analysis decided not to move forward with continuing the trial.
Study Start Date
November 7, 2018 (Actual)
Primary Completion Date
October 7, 2020 (Actual)
Study Completion Date
February 3, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Wake Forest University Health Sciences
Collaborators
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This phase II pilot trial studies how well gemcitabine and nivolumab work in treating participants with small cell lung cancer that has spread to other parts of the body after other treatments have failed. Drugs used in chemotherapy, such as gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as nivolumab, may interfere with the ability of tumor cells to grow and spread. Giving second-line gemcitabine and nivolumab may work better in treating participants with small cell lung cancer.
Detailed Description
PRIMARY OBJECTIVES: I. To compare response rate (RR) of gemcitabine and nivolumab (G+N) after 4 cycles (8 weeks) to historical controls treated with nivolumab alone. SECONDARY OBJECTIVES: I. To compare median overall survival (OS) of G+N to historical controls treated with nivolumab alone. II. To compare median progression-free survival (PFS) of G+N to historical controls treated with nivolumab alone. III. To evaluate for tolerability of G+N at each treatment cycle and then every 8 weeks after treatment is completed. EXPLORATORY OBJECTIVES: I. To correlate immunophenotypic changes among lymphocytes (quantitative measurements of CD4 and CD8 T-cells) with radiographic response and overall survival before treatment, after treatment and between 8-12 weeks after treatment. II. Among those patients with tumor mutation burden (TMB) status available, to describe the association between TMB (low, medium, or high) and RR, OS, and PFS. III. Assess the patient perspective of symptomatic adverse events using self-reported items from the National Cancer Institute (NCI) Patient Reported Outcomes-Common Terminology Criteria for Adverse Events (PRO-CTCAE). OUTLINE: Participants receive gemcitabine intravenously (IV) over 30 minutes and nivolumab IV over 60 minutes on day 1. Treatment repeats every 2 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, participants are followed up at 30 days, 6-10 weeks, and every 8 weeks thereafter.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Small Cell Lung Carcinoma, Stage IV Lung Cancer AJCC v8, Stage IVA Lung Cancer AJCC v8, Stage IVB Lung Cancer AJCC v8

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
14 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (gemcitabine, nivolumab)
Arm Type
Experimental
Arm Description
Participants receive gemcitabine IV over 30 minutes and nivolumab IV over 60 minutes on day 1. Treatment repeats every 2 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity
Intervention Type
Drug
Intervention Name(s)
Gemcitabine
Other Intervention Name(s)
dFdC, dFdCyd, Difluorodeoxycytidine
Intervention Description
Given IV
Intervention Type
Biological
Intervention Name(s)
Nivolumab
Other Intervention Name(s)
BMS-936558, MDX-1106, NIVO, ONO-4538, Opdivo
Intervention Description
Given IV
Primary Outcome Measure Information:
Title
Number of Participants With Positive Responses to Therapy Per Response Evaluation Criteria in Solid Tumors (RECIST)
Description
Objective RR (complete response [CR] + partial response [PR]) will be compared between this study sample and a historical benchmark value of 10%. For this comparison we will use a one-sample test of proportion. Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): Decrease by ≥ 30% in sum of longest diameter of target lesions. Stable Disease (SD): Not meeting criteria for CR, PR, or PD. Progressive Disease (PD): Increase by ≥ 20% in sum of longest diameter of target lesions or the appearance of one or more new lesions. The response in non-target lesions is defined as follows: Complete Response (CR): Complete disappearance of all non-target lesions. Stable Disease (SD): Persistence of one or more non-target lesion(s). Progressive Disease (PD): Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.
Time Frame
Up to 8 weeks
Secondary Outcome Measure Information:
Title
Overall Survival (OS) - Number of Participants
Description
OS will be estimated using standard Kaplan Meier survival analysis methods.
Time Frame
Duration of time from the start of treatment to date of death, assessed up to 2 years
Title
Overall Survival (OS) - Months
Description
A median value (months) of overall survival will be estimated using standard Kaplan Meier survival analysis methods.
Time Frame
Duration of time from the start of treatment to date of death, assessed up to 2 years
Title
Progression-free Survival (PFS) - Number of Participants
Description
Progression-free survival will be estimated using standard Kaplan Meier survival analysis methods. Progression-Free Survival (PFS) is defined as the duration of time from the start of treatment to the time of investigator assessed progression or death. Progressive Disease (PD): Increase by ≥ 20% in sum of longest diameter of target lesions or the appearance of one or more new lesions
Time Frame
Duration of time from the start of treatment to the time of investigator assessed progression or death, assessed up to 2 years
Title
Progression-free Survival (PFS) - Months
Description
A median value (months) of progressive-free survival will be estimated using standard Kaplan Meier survival analysis methods. Progressive Disease (PD): Increase by ≥ 20% in sum of longest diameter of target lesions or the appearance of one or more new lesions
Time Frame
Duration of time from the start of treatment to the time of investigator assessed progression or death, assessed up to 2 years
Title
Number of Adverse Events
Description
Toxicity rates will be estimated by responder status and presented overall and by body site per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
Time Frame
Up to 2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients must have histologically or cytologically confirmed incurable SCLC and have had prior treatment with platinum-based chemotherapy. High-grade neuroendocrine tumors that are suspected to be of bronchopulmonary origin can be enrolled if they have had prior treatment with a SCLC chemotherapy regimen (e.g. platinum plus etoposide). Patients should not be demonstrating end-organ damage due to rapid progression of disease based on the most recent assessment of the treating physician. Patients must have radiographically measurable metastatic disease by Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. Absolute neutrophil count >= 1,500/mcL. Platelets >= 100,000/mcL. Chemotherapy agents are known to be teratogenic, therefore women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. Ability to understand and the willingness to sign an Institutional Review Board (IRB)-approved informed consent document. Exclusion Criteria: Patients who have previously received either gemcitabine or an immune checkpoint inhibitor can be enrolled. Emergent need for palliative radiation. Patients may not be receiving any other investigational agents for the treatment of nonsmall cell lung cancer. History of allergic reaction to gemcitabine. Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. Pregnant women are excluded from this study because of the potential for teratogenic or abortifacient effects with chemotherapy. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with chemotherapy, breastfeeding should be discontinued.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Thomas W. Lycan
Organizational Affiliation
Wake Forest University Health Sciences
Official's Role
Principal Investigator
Facility Information:
Facility Name
Wake Forest University Health Sciences
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27157
Country
United States

12. IPD Sharing Statement

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Subsequent Line Gemcitabine and Nivolumab in Treating Participants With Metastatic Small Cell Lung Cancer

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