Ignite Creation Date:
2024-05-06 @ 6:40 PM
Last Modification Date:
2024-10-26 @ 2:52 PM
Study NCT ID:
NCT05746208
Status:
RECRUITING
Last Update Posted:
2023-12-19
First Post:
2023-02-17
Brief Title:
Lenvatinib Plus Pembrolizumab in Well Differentiated G3 Neuroendocrine Tumors
Sponsor:
University of California San Francisco
Organization:
University of California San Francisco
Study Overview
Official Title:
A Phase II Study of Lenvatinib Plus Pembrolizumab in Well Differentiated G3 Neuroendocrine Tumors
Status:
RECRUITING
Status Verified Date:
2023-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This is the first study to be done in a newly described class of neuroendocrine tumors known as well-differentiated grade 3 neuroendocrine tumors WD G3 NET First described in the pancreas in 2017 the classification was broadened to include gastrointestinal tract tumors in 2019 Recent data suggest an equivalent subtype exists in the lungs NEC with carcinoid morphology WD G3 NETs can occur de novo as well as the result of grade progression over time This is a single arm multi-site Phase II study in biomarker unselected participants This study will also incorporate serial blood samples tumor biopsies and special imaging to better understand the impact of therapy on the tumor and microenvironment Hyperpolarized HP 13C-pyruvate magnetic resonance imaging MRI - a novel non-radioactive imaging modality able to provide in vivo measurements of the pyruvate-to-lactate conversion rate kpl
Detailed Description:
PRIMARY OBJECTIVE
I To evaluate the overall response rate ORR of lenvatinib plus pembrolizumab
SECONDARY OBJECTIVES
I To determine the safety and tolerability of lenvatinib plus pembrolizumab II To evaluate the duration of response DOR in patients receiving lenvatinib plus pembrolizumab
III To evaluate progression-free survival PFS in patients receiving lenvatinib plus pembrolizumab
EXPLORATORY OBJECTIVES
I To evaluate overall survival OS in participants receiving lenvatinib plus pembrolizumab
II To compare overall response rate ORR DOR and PFS by Immune-related Response Evaluation Criteria In Solid Tumors irRECIST with the same measures assessed by Response Evaluation Criteria In Solid Tumors version 11
III To correlate clinical outcomes ORR DOR PFS OS with baseline immune cell infiltration T cell receptor TCR repertoires and programmed death-ligand 1 PD-L1 staining in pre-treatment biopsies IV To assess changes in immune cell infiltration PD-L1 staining and TCR repertoires in pre- and post-biopsies
V Correlate Ki67proliferative index with outcomes ORR DOR PFS OS
IV To characterize the baseline molecular features tissue- and blood-based of G3 NETs treated with lenvatinib and pembrolizumab
VII To correlate the molecular features of G3 NET with clinical outcomes eg responseresistance survival safety pharmacodynamic activity in the setting of treatment with pembrolizumab plus lenvatinib
VIII To describe the relationship between baseline tumor growth rate TGR and RECIST measurements for all patients
IX To examine changes in TGR over time in patients treated with Lenvatinib plus pembrolizumab TGR as assessed by cross-sectional imaging
X To investigate the relationship between on-treatment changes in pyruvate-to-lactate conversion rate kpl and ORR PFS and OS
XI To investigate the relationship between baseline tumor proliferative index as measured by Ki67 metabolic profile NMR spectroscopy and pyruvate-to-lactate conversion rate kpl as measured by hyperpolarized 13C-pyruvate imaging and ORR PFS and OS
XII Assessment of baseline heterogeneity of pyruvate-to-lactate conversion rate kpl between patients and between tumors within a given participant
OUTLINE
There are 2 stages to this study If at least 2 participants in stage 1 show a demonstrated response a second stage will open to enroll additional participants Participants may continue treatment for up to two years of therapy ie 18 doses of pembrolizumab
After the end of treatment each participant will be followed for 30 days for adverse event AE monitoring Serious adverse events SAE and events of clinical interest ECI will be collected for 90 days after the end of treatment or 30 days after the end of treatment if the participant initiates new anticancer therapy whichever is earlier Participants who discontinue for reasons other than progressive disease will have post-treatment follow-up for disease status until disease progression initiating a non-study cancer treatment withdrawing consent or becoming lost to follow-up After documented disease progression each participant will be followed by telephone for overall survival and anti-cancer therapy until death withdrawal of consent or the end of the study whichever occurs first
I To evaluate the overall response rate ORR of lenvatinib plus pembrolizumab
SECONDARY OBJECTIVES
I To determine the safety and tolerability of lenvatinib plus pembrolizumab II To evaluate the duration of response DOR in patients receiving lenvatinib plus pembrolizumab
III To evaluate progression-free survival PFS in patients receiving lenvatinib plus pembrolizumab
EXPLORATORY OBJECTIVES
I To evaluate overall survival OS in participants receiving lenvatinib plus pembrolizumab
II To compare overall response rate ORR DOR and PFS by Immune-related Response Evaluation Criteria In Solid Tumors irRECIST with the same measures assessed by Response Evaluation Criteria In Solid Tumors version 11
III To correlate clinical outcomes ORR DOR PFS OS with baseline immune cell infiltration T cell receptor TCR repertoires and programmed death-ligand 1 PD-L1 staining in pre-treatment biopsies IV To assess changes in immune cell infiltration PD-L1 staining and TCR repertoires in pre- and post-biopsies
V Correlate Ki67proliferative index with outcomes ORR DOR PFS OS
IV To characterize the baseline molecular features tissue- and blood-based of G3 NETs treated with lenvatinib and pembrolizumab
VII To correlate the molecular features of G3 NET with clinical outcomes eg responseresistance survival safety pharmacodynamic activity in the setting of treatment with pembrolizumab plus lenvatinib
VIII To describe the relationship between baseline tumor growth rate TGR and RECIST measurements for all patients
IX To examine changes in TGR over time in patients treated with Lenvatinib plus pembrolizumab TGR as assessed by cross-sectional imaging
X To investigate the relationship between on-treatment changes in pyruvate-to-lactate conversion rate kpl and ORR PFS and OS
XI To investigate the relationship between baseline tumor proliferative index as measured by Ki67 metabolic profile NMR spectroscopy and pyruvate-to-lactate conversion rate kpl as measured by hyperpolarized 13C-pyruvate imaging and ORR PFS and OS
XII Assessment of baseline heterogeneity of pyruvate-to-lactate conversion rate kpl between patients and between tumors within a given participant
OUTLINE
There are 2 stages to this study If at least 2 participants in stage 1 show a demonstrated response a second stage will open to enroll additional participants Participants may continue treatment for up to two years of therapy ie 18 doses of pembrolizumab
After the end of treatment each participant will be followed for 30 days for adverse event AE monitoring Serious adverse events SAE and events of clinical interest ECI will be collected for 90 days after the end of treatment or 30 days after the end of treatment if the participant initiates new anticancer therapy whichever is earlier Participants who discontinue for reasons other than progressive disease will have post-treatment follow-up for disease status until disease progression initiating a non-study cancer treatment withdrawing consent or becoming lost to follow-up After documented disease progression each participant will be followed by telephone for overall survival and anti-cancer therapy until death withdrawal of consent or the end of the study whichever occurs first
Study Oversight
Has Oversight DMC:
None
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?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| NCI-2023-01199 | REGISTRY | NCI Clinical Trials Reporting Program CTRP | None |