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Quick Start Durvalumab Following Chemoradiation for Stage III Nonsmall Cell Lung Cancer

Phase 2
Recruiting
Conditions
Nonsmall Cell Lung Cancer Stage III
Unresectable Non-Small Cell Lung Carcinoma
Nonsmall Cell Lung Cancer, Stage II
Interventions
Other: the EORTC Core Quality of Life Questionnaire (EORTC QLQ-C30)
Diagnostic Test: COPD Assessment Test (CAT)
Diagnostic Test: Modified Medical Research Council (mMRC) dyspnea scale
Registration Number
NCT05696782
Lead Sponsor
Wake Forest University Health Sciences
Brief Summary

This research study aims to determine what effects (good and bad) Durvalumab has on participants and their cancer with a "quick start" of Durvalumab within 14 days of finishing chemotherapy and radiation. The study will also determine the logistic barriers to the quick start of Durvalumab.

Detailed Description

Primary Objective: Assess the treatment fidelity for early Durvalumab initiation (i.e., within 14 days after the last day of radiation therapy) following chemoradiation for unresectable Stage II or Stage III nonsmall cell lung cancer.

Secondary Objectives:

* Assess the treatment fidelity for very early Durvalumab initiation (i.e., within seven days after the last day of radiation therapy) following chemoradiation for unresectable Stage II or Stage III nonsmall cell lung cancer.

* Assess barriers to earlier Durvalumab initiation following chemoradiation for unresectable Stage II or Stage III nonsmall cell lung cancer.

* Describe the toxicity of Durvalumab when initiated quickly after chemoradiation for unresectable Stage II or Stage III nonsmall cell lung cancer as compared to historical controls.

* Describe the efficacy of Durvalumab when initiated quickly after chemoradiation for unresectable Stage II or Stage III nonsmall cell lung cancer as compared to historical controls.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
28
Inclusion Criteria
  • Patients must have Stage II or Stage III nonsmall cell lung cancer confirmed by histologic or cytologic documentation and by clinical assessment. Staging is defined according to the American Joint Committee on Cancer Staging Manual, 8th Edition (2017).
  • Unresectable or medically inoperable as determined by the investigator.
  • The participant has definitive radiation therapy (e.g., 54 Gy to 66 Gy in 30 to 35 fractions) for lung cancer that is either (a) planned to start within the next 28 days, or (b) currently being administered, or (c) has been completed within the last 14 days.
  • Platinum-based chemotherapy for lung cancer that is either (a) planned to start within the next 28 days, (b) currently being administered, or (c) has been completed within the last 14 days. Chemotherapy must be for at least two cycles and be administered either before radiation therapy ("induction" or "sequential") or during radiation therapy ("concurrent").
  • Consolidation Durvalumab is planned for nonsmall cell lung cancer after radiation and chemotherapy.
  • Eighteen years old or greater.
  • ECOG performance status of 0-2.
  • Life expectancy of greater than three months.
  • Patients with sexual relationships in which either they or their partner may become pregnant must use contraception during the study treatment period.
  • Ability to understand and be willing to sign an IRB-approved informed consent document directly or via a legally authorized representative.
Exclusion Criteria
  • Uncontrolled respiratory symptoms (i.e., cough, dyspnea, fevers, chest pain, or an increase from baseline oxygen requirements) that are interfering with activities of daily living.
  • Nonsmall cell lung cancer is known to have a tumor with a mutation in EGFR associated with sensitivity to first-line therapy with a tyrosine kinase inhibitor (i.e., Ex19del or L858R). Testing for EGFR mutation must have been attempted for study enrollment. If EGFR testing is inconclusive (e.g., the biopsy's quantity or quality is not sufficient for testing to be performed) and there is low clinical suspicion for the presence of an EGFR mutation as determined by the investigator, then the patient is eligible.
  • Prior exposure to an immune checkpoint inhibitor targeting CTLA-4, PD-1, or PD-L1.
  • Active autoimmune disease requiring systemic immunosuppression at the time of enrollment.
  • History of autoimmune pneumonitis requiring high-dose systemic steroids (equivalent prednisone >20 mg/day for more than one week).
  • Uncontrolled intercurrent illness includes 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.
  • Patients who are pregnant or breastfeeding.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Quick Start Durvalumabthe EORTC Core Quality of Life Questionnaire (EORTC QLQ-C30)Standard of care test and procedures for cancer treatments along with Durvalumab treatment at physician's discretion
Quick Start DurvalumabCOPD Assessment Test (CAT)Standard of care test and procedures for cancer treatments along with Durvalumab treatment at physician's discretion
Quick Start DurvalumabModified Medical Research Council (mMRC) dyspnea scaleStandard of care test and procedures for cancer treatments along with Durvalumab treatment at physician's discretion
Quick Start DurvalumabDurvalumabStandard of care test and procedures for cancer treatments along with Durvalumab treatment at physician's discretion
Primary Outcome Measures
NameTimeMethod
Number of Participants to Achieve Fidelity to Early Treatment with Durvalumab - Early Initiation (1-14 days)48 weeks

Fidelity is defined as a dichotomous composite indicator (yes/no) that describes whether the patient received very early (1-7 days) initiation of Durvalumab as per protocol with all four of the following criteria having been met: (i) CT chest obtained after the last day of radiation therapy and before the first infusion of Durvalumab, (ii) first infusion within 14 days of completing radiation therapy, (iii) second and third doses received within 63 days of the first dose, and (iv) all infusions at least 28 days apart.

Secondary Outcome Measures
NameTimeMethod
Overall SurvivalOne year

Using Kaplan-Meier life table methods, overall survival is defined as the number of participants alive at 12 months after the first dose of Durvalumab.

Number of Participants to Achieve Fidelity to Early Treatment with Durvalumab - Very Early (1-7 days)Up to 13 months

Fidelity is defined as a dichotomous composite indicator (yes/no) that describes whether the patient received very early (1-7 days) initiation of Durvalumab as per protocol with all four of the following criteria having been met: (i) CT chest obtained after the last day of radiation therapy and before the first infusion of Durvalumab, (ii) first infusion within 7 days of completing radiation therapy, (iii) second and third doses received within 63 days of the first dose, and (iv) all infusions at least 28 days apart.

Progression-Free SurvivalOne year

Using Kaplan-Meier methods, progression-free survival is defined as the number of participants alive and without disease progression as documented by the treating provider at 12 months after the first dose of Durvalumab.

Number of Participants to Discontinue Durvalumab Due to Adverse EventsOne year

Participants with early fidelity who discontinue Durvalumab at any point due to an adverse event of any cause and compare it using a one-sample test of proportions.

Response RateOne year

Best objective response rate (ORR) to Durvalumab is defined by either a complete response (CR) or partial response (PR) as per RECIST 1.1 criteria by investigator assessment and confirmed on at least two sequential imaging studies that are at least four weeks apart.

* Complete Response (CR): Disappearance of all target lesions.

* Partial Response (PR): Decrease by ≥ 30% in sum of longest diameter of target lesions.

Number of Barriers to Initiation of Durvalumab - Very Early (Days 1-7)Up to 13 months

Descriptive frequencies of participant survey answers will be examined to conduct qualitative analyses and determine appropriate categories of answers on the free text responses. We will examine barriers/obstacles for everyone in the sample, even those who achieve fidelity; such patients could have experienced delays even if they were still able to achieve fidelity. We will stratify answers/responses by fidelity status.

Number of Barriers to Initiation of Durvalumab - Early (Days 8-14)Up to 13 months

Descriptive frequencies of participant survey answers will be examined to conduct qualitative analyses and determine appropriate categories of answers on the free text responses. We will examine barriers/obstacles for everyone in the sample, even those who achieve fidelity; such patients could have experienced delays even if they were still able to achieve fidelity. We will stratify answers/responses by fidelity status.

Number of Participants with All Adverse EventsUp to 13 months after intervention

Adverse events, serious adverse events and immune-related adverse events will be tabulated by fidelity status (1-7 days vs. 8-14 days vs. neither) using National Cancer Institute Common Terminology Criteria, version 5.0.

Number of Participants Who Have Immune-Mediated Pneumonitis - Early Fidelity (1-14 days)Within 85 days of intervention (Cycles 1-3)

Participants with early (1-14 days) fidelity who have immune-mediated early-onset pneumonitis will be estimated and statistically compared in a one-sample test of proportions.

Number of Participants Who Have All-Cause Any Grade Pneumonitis - Early Fidelity (1-14 days)Within 85 days of intervention (Cycles 1-3)

Participants with all-cause early-onset pneumonitis among those with early (1-14 days) fidelity and statistically compare it, using a one-sample test of proportions.

Trial Locations

Locations (1)

Wake Forest Baptist Comprehensive Cancer Center

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Winston-Salem, North Carolina, United States

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