Ignite Creation Date:
2025-12-25 @ 5:04 AM
Ignite Modification Date:
2025-12-26 @ 4:06 AM
Study NCT ID:
NCT05589818
Status:
RECRUITING
Last Update Posted:
2025-06-25
First Post:
2022-09-26
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Pembrolizumab for Advanced NSCLC and PS 2-3
Sponsor:
Icahn School of Medicine at Mount Sinai
Organization:
Study Overview
Official Title:
A Phase II Study of the Effects of Pembrolizumab on Quality of Life for Patients With Treatment-Naïve, Advanced or Metastatic NSCLC and Poor Performance Status
Status:
RECRUITING
Status Verified Date:
2025-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This single center open-label trial will enroll a single cohort of patients with advanced non-small cell lung cancer (NSCLC) who are ineligible for treatment with curative intent due to 1) disease stage IV, or 2) inability to tolerate intensive surgery or chemo-radiation. Patients will be eligible for the trial if ISMMS reviewed samples from tumor biopsy have a PDL-1 TPS ≥ 1% and have ECOG performance status rated 2 or 3. All patients will receive anti PD-1 therapy with pembrolizumab 200mg IV every 3 weeks, during which patients will also undergo serial QOL assessments.
This trial will follow a phase II single arm, open label design. The study will enroll 45 patients evaluable for the primary endpoint of which will be change in QOL as measured by the EORTC's QLQ-C30 between Day 1 and Day 84 +/- 7 days. Secondary outcomes including evaluation for development of confounding mental health conditions will be evaluated via serial HADS assessments. Concomitant radiographic assessment with PET/CT, regardless of the doses of pembrolizumab received, will allow for evaluation of secondary efficacy outcomes, including disease response by RECIST 1.1 criteria.
This trial will follow a phase II single arm, open label design. The study will enroll 45 patients evaluable for the primary endpoint of which will be change in QOL as measured by the EORTC's QLQ-C30 between Day 1 and Day 84 +/- 7 days. Secondary outcomes including evaluation for development of confounding mental health conditions will be evaluated via serial HADS assessments. Concomitant radiographic assessment with PET/CT, regardless of the doses of pembrolizumab received, will allow for evaluation of secondary efficacy outcomes, including disease response by RECIST 1.1 criteria.
Detailed Description:
Primary Objective To assess the effects of first-line pembrolizumab upon patient quality of life in patients with metastatic non-small cell lung cancer who are ineligible for standard first line treatments due to poor performance status (ECOG PS of 2 or 3).
Secondary Objectives
* To assess the clinical outcomes of first-line pembrolizumab in this patient population.
* To evaluate the toxicity of first-line pembrolizumab in this patient population.
* To assess patient reported QOL in the emotional domain (using HADS).
* To assess baseline patient-reported performance status and correlate with QOL and clinical outcomes.
* To assess baseline geriatric assessment score for patients 70 years of age and older and correlate with QOL and clinical outcomes.
* To correlate QOL and outcomes with demographic and clinical factors including: age, gender, race/ethnicity, zip code, insurance type, presence/absence of CNS metastases, PD-L1 TPS (\<1%, 1-49%, ≥50%), geriatric assessment scores, presence or absence of other major organ dysfunction (e.g. CKD), ECOG 2 vs 3, adverse events: G2, G3-4.
Primary Endpoint Change in QOL score after 12 weeks of treatment as measured by EORTC's QLQ-C30
Secondary Endpoints
* Change in QOL score after 6 weeks of treatment as measured by EORTC's QLQ-C30
* Change in QOL score after 6 and 12 weeks of treatment as measured by EORTC's QLQ-LC13.
* Change in QOL score in the emotional domain after 6 and 12 weeks of treatment as measured by HADS
* Overall survival
* Objective response rate, as determined by independent radiology review and assessed using the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1, at 12 weeks after treatment
* Progression free survival
* Emergency room visits and hospitalizations
* Adverse events, as assessed by the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
* Patient reported ECOG performance status and correlation with QOL and clinical outcomes.
* Treating physician clinical assessment of whether poor PS, as measured by the ECOG Performance Status Scale, is due to disease, other comorbidities, or both and correlation with QOL and clinical outcomes
* Geriatric assessment at baseline for patients 70 years of age and older and correlation with QOL and clinical outcomes, using the Cancer Aging and Research Group (CARG) Chemo-Toxicity Calculator Survey https://www.mycarg.org/?page\_id=4480
* Patient Reported Outcome (PRO) completion rate
* Difference in QOL score objective response proportion (CR + PR), and OS at 12 weeks between categories of:
* Age group
* Gender
* Race/ethnicity
* Zip code
* Insurance type
* Presence/absence of CNS metastases
* PD-L1 (TPS \<1%, 1-49%, ≥50%)
* Geriatric assessment scores
* Presence or absence of other major organ dysfunction
* ECOG PS 2 vs 3
* Adverse events G2, G3-4
Study Drug, Dose, Route, and Regimen: Pembrolizumab 200 mg IV every 3 weeks for 12 weeks, with the option to transition to pembrolizumab 400 mg IV every 6 weeks thereafter. Pembrolizumab will then be continued until disease progression, unacceptable toxicity, withdrawal of consent, or death.
Statistical Considerations: This is a phase II clinical trial to assess the change in Quality of Life (QoL), measured by EORTC QLQ-C30 scores, for patients with treatment-naïve, advanced or metastatic NSCLC and ECOG 2/3 on Pembrolizumab treatment. The global QoL (QLQ-30) at baseline in 218 lung cancer patients had a mean of 57.6 and standard deviation (SD) of 24.3. The research team will test the difference in the change in QoL score between baseline and 12 weeks after Pembrolizumab treatment. A meaningful change, as documented in the literature, has determined to be a 10 score difference. The SD of the change is 18.9, assuming that the pre-/post- correlation is 0.7. A sample of 31 achieves 81% power to detect a mean of paired differences of 10 with an estimated SD of differences of 18.9 and with a significance level of 0.05 using a two-sided paired t-test. Considering the potential 30% drop-out, this study will enroll 45 patients to ensure at least 31 evaluable patients.
Approximately 20 new patients with metastatic NSCLC are seen per month at the Mount Sinai Hospital and Mount Sinai Chelsea sites; of these, approximately 7-8 have a PS of 2-3 based on past experience. Thus, the study can reasonably expect to accrue 2 patients per month to the study, with approximately 24 months needed to complete accrual.
Total number of participants: 45 Estimated Enrollment Period: 24 Months Estimated Duration of Participation: 24 Months Estimated Study Duration: 40 Months Participating Sites: Mount Sinai Hospital and Mount Sinai Chelsea
Secondary Objectives
* To assess the clinical outcomes of first-line pembrolizumab in this patient population.
* To evaluate the toxicity of first-line pembrolizumab in this patient population.
* To assess patient reported QOL in the emotional domain (using HADS).
* To assess baseline patient-reported performance status and correlate with QOL and clinical outcomes.
* To assess baseline geriatric assessment score for patients 70 years of age and older and correlate with QOL and clinical outcomes.
* To correlate QOL and outcomes with demographic and clinical factors including: age, gender, race/ethnicity, zip code, insurance type, presence/absence of CNS metastases, PD-L1 TPS (\<1%, 1-49%, ≥50%), geriatric assessment scores, presence or absence of other major organ dysfunction (e.g. CKD), ECOG 2 vs 3, adverse events: G2, G3-4.
Primary Endpoint Change in QOL score after 12 weeks of treatment as measured by EORTC's QLQ-C30
Secondary Endpoints
* Change in QOL score after 6 weeks of treatment as measured by EORTC's QLQ-C30
* Change in QOL score after 6 and 12 weeks of treatment as measured by EORTC's QLQ-LC13.
* Change in QOL score in the emotional domain after 6 and 12 weeks of treatment as measured by HADS
* Overall survival
* Objective response rate, as determined by independent radiology review and assessed using the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1, at 12 weeks after treatment
* Progression free survival
* Emergency room visits and hospitalizations
* Adverse events, as assessed by the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
* Patient reported ECOG performance status and correlation with QOL and clinical outcomes.
* Treating physician clinical assessment of whether poor PS, as measured by the ECOG Performance Status Scale, is due to disease, other comorbidities, or both and correlation with QOL and clinical outcomes
* Geriatric assessment at baseline for patients 70 years of age and older and correlation with QOL and clinical outcomes, using the Cancer Aging and Research Group (CARG) Chemo-Toxicity Calculator Survey https://www.mycarg.org/?page\_id=4480
* Patient Reported Outcome (PRO) completion rate
* Difference in QOL score objective response proportion (CR + PR), and OS at 12 weeks between categories of:
* Age group
* Gender
* Race/ethnicity
* Zip code
* Insurance type
* Presence/absence of CNS metastases
* PD-L1 (TPS \<1%, 1-49%, ≥50%)
* Geriatric assessment scores
* Presence or absence of other major organ dysfunction
* ECOG PS 2 vs 3
* Adverse events G2, G3-4
Study Drug, Dose, Route, and Regimen: Pembrolizumab 200 mg IV every 3 weeks for 12 weeks, with the option to transition to pembrolizumab 400 mg IV every 6 weeks thereafter. Pembrolizumab will then be continued until disease progression, unacceptable toxicity, withdrawal of consent, or death.
Statistical Considerations: This is a phase II clinical trial to assess the change in Quality of Life (QoL), measured by EORTC QLQ-C30 scores, for patients with treatment-naïve, advanced or metastatic NSCLC and ECOG 2/3 on Pembrolizumab treatment. The global QoL (QLQ-30) at baseline in 218 lung cancer patients had a mean of 57.6 and standard deviation (SD) of 24.3. The research team will test the difference in the change in QoL score between baseline and 12 weeks after Pembrolizumab treatment. A meaningful change, as documented in the literature, has determined to be a 10 score difference. The SD of the change is 18.9, assuming that the pre-/post- correlation is 0.7. A sample of 31 achieves 81% power to detect a mean of paired differences of 10 with an estimated SD of differences of 18.9 and with a significance level of 0.05 using a two-sided paired t-test. Considering the potential 30% drop-out, this study will enroll 45 patients to ensure at least 31 evaluable patients.
Approximately 20 new patients with metastatic NSCLC are seen per month at the Mount Sinai Hospital and Mount Sinai Chelsea sites; of these, approximately 7-8 have a PS of 2-3 based on past experience. Thus, the study can reasonably expect to accrue 2 patients per month to the study, with approximately 24 months needed to complete accrual.
Total number of participants: 45 Estimated Enrollment Period: 24 Months Estimated Duration of Participation: 24 Months Estimated Study Duration: 40 Months Participating Sites: Mount Sinai Hospital and Mount Sinai Chelsea
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?: