Trial Outcomes & Findings for Induction of Sensecence Using Dexamethasone to Re-sensitize NSCLC to Anti-PD1 Therapy (NCT NCT04037462)

Last Updated: 2024-06-14

Results Overview

In the first stage, three Dex escalation cohorts will be evaluated sequentially from Cohort A to Cohort C until \> 2 patients exhibit FLT-PET response (i.e., 30% reduction in FLT-PET uptake in at least one target lesion); otherwise, the trial will be terminated due to futility. The SUVmax will be measured at baseline and after Dex run-in and wash out period. For example, in Cohort A, patients will get an FLT- PET at baseline, then receive Dexamethasone 4mg PO BID given for 7 days, followed by taper over 2-4 days and 3 day wash out and then the post-Dex FLT-PET.

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

2 participants

Primary outcome timeframe

Baseline and Post DEX (14 days)

Results posted on

2024-06-14

Participant Flow

Recruitment start date July 7, 2021, consented 3 participant from the medical oncology clinic. 1 participant rescinded consent and was never enrolled therefore, we only enrolled 2 participants start shut down during COVID 2020-21 Pt 1: 7-7-2021 Pt 2: 8-30-2021 (rescinded consent due to logistical burden) Pt 3: 1-05-2022

Pt 2 rescinded consent due to logistical burden

Participant milestones

Participant milestones
Measure	Lead in Dexamethasone Followed by Immunotherapy lead in cohort consisted of patients who failed initial immunotherapy and were assigned to dose level 1: dexamethasone 4 mg p.o b.i.d days 1-7 to assess 1. changes in FLT PET uptake 2. assess overall response rates of pretreatment dexamethasone on subsequent immunotherapy re-challenge.
Overall Study STARTED	2
Overall Study COMPLETED	2
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Induction of Sensecence Using Dexamethasone to Re-sensitize NSCLC to Anti-PD1 Therapy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Lead in Dexamethasone Followed by Immunotherapy n=2 Participants escalating doses of pretreatment dexamethasone in patients who have failed initial immunotherapy to 1. assess changes in FLT PET uptake 2. assess overall response rates of pretreatment dexamethasone (dose from 1) on subsequent immunotherapy re-challenge Dexamthasone: escalating doses of pretreatment dexamethasone in patients who have failed initial immunotherapy to 1. assess changes in FLT PET uptake 2. assess overall response rates of pretreatment dexamethasone (dose from 1) on subsequent immunotherapy re-challenge
Age, Customized greater than or equal to 18	2 years n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants
Sex: Female, Male Male	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	2 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Post DEX (14 days)

Outcome measures

Outcome measures
Measure	Lead in Dexamethasone Followed by Immunotherapy n=2 Participants escalating doses of pretreatment dexamethasone in patients who have failed initial immunotherapy to 1. assess changes in FLT PET uptake 2. assess overall response rates of pretreatment dexamethasone (dose from 1) on subsequent immunotherapy re-challenge Dexamthasone: escalating doses of pretreatment dexamethasone in patients who have failed initial immunotherapy to 1. assess changes in FLT PET uptake 2. assess overall response rates of pretreatment dexamethasone (dose from 1) on subsequent immunotherapy re-challenge Due to accrual of 2 participants there is not enough data to state efficacy.
Change in Fluoro-3' Deoxythymidine Positron Emission Tomography (FLT-PET) Signal Baseline	6.63 SUVmax Standard Deviation .95
Change in Fluoro-3' Deoxythymidine Positron Emission Tomography (FLT-PET) Signal Post DEX	6.05 SUVmax Standard Deviation 1.24

SECONDARY outcome

Timeframe: 3 months

Population: Overall response rate will be assessed at 12 week FDG PET scan

The primary objective in SA 2 is to assess the effect of Dex on pembrolizumab in terms of overall response rate (ORR). Based on pre-clinical and clinical studies, the investigators hypothesize that the true ORR of Dex followed by pembrolizumab will be at least 33% (i.e., p1 = 0.33) vs. the historical control whose ORR is at most 7% (i.e., p0 = 0.07). The ORR will be statistically evaluated when the FLT-PET response trial enters the third stage, where the number of patients with the selected optimal Dex duration will be 21. Otherwise, ORR will be summarized descriptively. The null hypothesis (p0 = 7%) will be rejected if five or more responses are observed in 21 patients, which yields a 1-sided type I error rate of 5% and power of 87% when the true ORR is 33% (i.e. p1 = 33%).

Outcome measures

Outcome measures
Measure	Lead in Dexamethasone Followed by Immunotherapy n=1 Participants escalating doses of pretreatment dexamethasone in patients who have failed initial immunotherapy to 1. assess changes in FLT PET uptake 2. assess overall response rates of pretreatment dexamethasone (dose from 1) on subsequent immunotherapy re-challenge Dexamthasone: escalating doses of pretreatment dexamethasone in patients who have failed initial immunotherapy to 1. assess changes in FLT PET uptake 2. assess overall response rates of pretreatment dexamethasone (dose from 1) on subsequent immunotherapy re-challenge Due to accrual of 2 participants there is not enough data to state efficacy.
Response Rate	1 Participants

Adverse Events

Lead in Dexamethasone Followed by Immunotherapy

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Nithya Ramnath

VA Ann Arbor Healthcare System

Phone: (734) 845-5800

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place