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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03662074
Recruitment Status : Active, not recruiting
First Posted : September 7, 2018
Last Update Posted : October 19, 2020
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Wake Forest University Health Sciences

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.

Condition or disease Intervention/treatment Phase
Small Cell Lung Carcinoma Stage IV Lung Cancer AJCC v8 Stage IVA Lung Cancer AJCC v8 Stage IVB Lung Cancer AJCC v8 Drug: Gemcitabine Biological: Nivolumab Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 14 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Pilot Study of Subsequent Line Gemcitabine and Nivolumab for Advanced SCLC
Actual Study Start Date : November 7, 2018
Actual Primary Completion Date : October 7, 2020
Estimated Study Completion Date : August 2022


Arm Intervention/treatment
Experimental: Treatment (gemcitabine, nivolumab)
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
Drug: Gemcitabine
Given IV
Other Names:
  • dFdC
  • dFdCyd
  • Difluorodeoxycytidine

Biological: Nivolumab
Given IV
Other Names:
  • BMS-936558
  • MDX-1106
  • NIVO
  • ONO-4538
  • Opdivo




Primary Outcome Measures :
  1. Radiographic response rate (RR) per Response Evaluation Criteria in Solid Tumors (RECIST) [ Time Frame: Up to 8 weeks ]
    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.


Secondary Outcome Measures :
  1. Overall survival (OS) [ Time Frame: Duration of time from the start of treatment to date of death, assessed up to 2 years ]
    OS will be estimated using standard Kaplan Meier survival analysis methods.

  2. Progression-free survival (PFS) [ Time Frame: Duration of time from the start of treatment to the time of investigator assessed progression or death, assessed up to 2 years ]
    PFS will be estimated using standard Kaplan Meier survival analysis methods.

  3. Incidence of adverse events per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 [ Time Frame: Up to 2 years ]
    Toxicity rates will be estimated by responder status and presented overall and by body site.


Other Outcome Measures:
  1. Immunophenotypic changes among lymphocytes (CD4 versus CD8) [ Time Frame: Baseline, post-treatment, and at 6-10 weeks ]
    Will assess association between clinical outcomes (RR, OS, PFS) with immunophenotypic changes among lymphocytes. Changes in T regulatory cell concentrations will be assessed in each arm. These measures will be compared longitudinally to examine whether changes in certain biomarkers are associated with participants who experience an objective response. Peripheral blood samples at 3 time points (baseline before study treatment, post-treatment, and at follow-up [between 6 and 10 weeks post-treatment]) will be analyzed by flow cytometry.

  2. Tumor mutation burden (TMB) [ Time Frame: Up to 2 years ]
    Will assess clinical outcomes (RR, OS, PFS) and association with TMB. Assessed as (low, 0 to < 143; medium, 143 to 247; or high, > 248). TMB status (low, medium, or high) will be assessed as to how they relate to RR, OS, and PFS. This subgroup analysis will be in a descriptive manner only due to the small size of the study.

  3. Participant responses to (Patient Reported Outcomes) PRO-CTCAE items [ Time Frame: Baseline up to 2 years ]
    Participants self-reported symptoms will be assessed with PRO-CTCAE at patient preference; these scores will be analyzed in a descriptive manner only due to the small size of the study.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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:

  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03662074


Locations
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United States, North Carolina
Wake Forest University Health Sciences
Winston-Salem, North Carolina, United States, 27157
Sponsors and Collaborators
Wake Forest University Health Sciences
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Thomas W. Lycan Wake Forest University Health Sciences
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Responsible Party: Wake Forest University Health Sciences
ClinicalTrials.gov Identifier: NCT03662074    
Other Study ID Numbers: IRB00051024
NCI-2018-01803 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
CCCWFU 62418 ( Other Identifier: Wake Forest University Health Sciences )
P30CA012197 ( U.S. NIH Grant/Contract )
First Posted: September 7, 2018    Key Record Dates
Last Update Posted: October 19, 2020
Last Verified: October 2020

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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
Additional relevant MeSH terms:
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Lung Neoplasms
Small Cell Lung Carcinoma
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Gemcitabine
Nivolumab
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Immunological