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

NCT ID: NCT03662074

Last Updated: 2023-08-02

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 14 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-11-07
• Study Completion Date: 2022-02-03

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.

Conditions

Small Cell Lung Carcinoma; Stage IV Lung Cancer AJCC v8; Stage IVA Lung Cancer AJCC v8; Stage IVB Lung Cancer AJCC v8

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

Gemcitabine

Intervention Type: DRUG

Given IV

Nivolumab

Intervention Type: BIOLOGICAL

Given IV

Interventions

Gemcitabine

Given IV

Intervention Type: DRUG

Nivolumab

Given IV

Intervention Type: BIOLOGICAL

Other Intervention Names

dFdC; dFdCyd; Difluorodeoxycytidine; BMS-936558; MDX-1106; NIVO; ONO-4538; Opdivo

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Wake Forest University Health Sciences

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Thomas W. Lycan

Role: PRINCIPAL_INVESTIGATOR

Wake Forest University Health Sciences

Locations

Wake Forest University Health Sciences

Winston-Salem, North Carolina, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

NCI-2018-01803

Identifier Type: REGISTRY

Identifier Source: secondary_id

CCCWFU 62418

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA012197

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IRB00051024

Identifier Type: -

Identifier Source: org_study_id