Astellas Exit Survey Study
Research type
Research Study
Full title
A Noninterventional Exit Survey Study to Understand Meaningful Change in Subjects with Claudin (CLDN)18.2-Positive, HER2-Negative, Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma who Discontinued Treatment in the SPOTLIGHT or GLOW Study
IRAS ID
314326
Contact name
Tami Jo Larson
Contact email
Sponsor organisation
Astellas Pharma Global Development, Inc.
Duration of Study in the UK
0 years, 0 months, 31 days
Research summary
Gastric cancer-related mortality is the fourth leading cause of cancer death worldwide, even though its incidence has decreased over past decades in different regions of the world.
Zolbetuximab (IMAB362) is being developed with the goal of addressing the unmet medical need of extending progression-free and overall survival in advanced gastric and Gastroesophageal Junction (GEJ) adenocarcinoma.
To establish these thresholds, it is important to understand from the participants’ perspective what they consider to be a meaningful and significant change in abdominal pain, physical functioning, and overall quality of life once having completed the primary research in either the SPOTLIGHT (8951-CL-0301) or GLOW study (8951-CL-0302) both of which are Phase 3 studies.After either the SPOTLIGHT or GLOW study drug discontinuation visit the participant will be asked to take part in this online exit survey study, and to consent. The participant will need to have stopped taking both study drugs (zolbetuximab or placebo AND backbone chemotherapy) in the SPOTLIGHT or GLOW study to take part in this one. If study drug was discontinued on different days and two study drug discontinuation visits occurred, the later discontinuation visit date will be used for purposes of this exit survey study. Both you and the study site personnel will remain blinded to treatment assignment from the SPOTLIGHT or GLOW study.
After the participant’s consent, site personnel will submit contact details (that includes their SPOTLIGHT or GLOW study subject identification (ID) number, email address, country of residence, preferred language, and date of study drug discontinuation visit) to a secure, username-controlled portal confirming their willingness to take part. A “subject information sheet” will be provided which will explain the study and have information on how to access and complete the online exit survey via a secure platform within 30 days following the SPOTLIGHT or GLOW study drug discontinuation visit.
Completion of the online survey through a smart-phone, tablet, or computer. There are 16 questions across 6 different screens. The survey should take up to 10 minutes to complete.
Lay summary of study results: A noninterventional exit survey study was conducted to understand meaningful change in subjects with claudin (CLDN) 18.2-positive, HER2-negative, locally advanced unresectable or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma who discontinued all study treatment in the SPOTLIGHT or GLOW study. The SPOTLIGHT and GLOW studies are two multi-center, parallel group, double-blind, randomized, placebo-controlled studies to evaluate the use of zolbetuximab plus mFOLFOX6 (SPOTLIGHT-8951-CL-0301) or zolbetuximab plus capecitabine and oxaliplatin (CAPOX) (GLOW-8951-CL-0302) as first-line treatment in subjects with CLDN18.2- positive, HER2-negative locally advanced unresectable or metastatic gastric and GEJ adenocarcinoma.
Several clinical outcome assessments (COAs) were included as part of the SPOTLIGHT and GLOW studies to assess meaningful change thresholds for measures of 3 areas of health related quality of life (HRQoL), including: European Organization for Research and Treatment of Cancer (EORTC) Quality of Life of Cancer Patients, core questionnaire (QLQ C30) Global Health Status (GHS) / Quality of Life (QoL) and Physical Functioning (PF) and EORTC Quality of Life Questionnaire-Gastric Module (QLQ-OG25) Abdominal Pain and discomfort scores.
Demographic and Other Baseline Characteristics The full analysis set (FAS) included 30 patients (median age: 61 years, 60.0% male). The majority of patients who reported race were White (59.3%) or Asian (40.7%). All patients had an ECOG performance status of 0 (53.3%) or 1 (46.7%). Among the 30 patients, one patient was missing the baseline EORTC assessment and another two patients were missing the EORTC data at end of treatment (EOT), resulting in 27 patients with available EORTC scores for the anchor-based analyses.
EORTC QLQ-C30 GHS/QoL
The half standard deviation (SD) of EORTC QLQ-C30 GHS/QoL at baseline were estimated at 9.11. Correlations between change in GHS/QoL and the anchor was sufficient (absolute value r > 0.37). The 95% CI for the 11 patients reporting ‘no change’ on the PGIC-type Item 8 was between -20.02 and 7.90 points with the median change of 0.00 points (mean change = -6.06). The upper 95% confidence interval (CI) (indicating improvement) for patients reporting ‘no change’ on the anchor was 7.90 which supports the improvement threshold (primary time to improvement [TTI] threshold = 8), while the median change in GHS/QoL score was larger at 16.67 (n = 13).
EORTC QLQ-C30 Physical Functioning
The half SD of EORTC QLQ-C30 Physical Functioning scores at baseline were estimated at 8.10. Correlations between change in Physical Functioning and the anchor were sufficient (absolute value r > 0.37). For patients with ‘no change’ on the PGIC-type Item 6 (n = 10), the mean Physical Functioning scores slightly worsened by -1.33 points (median change: 0.00; 95% CI: -6.26; 3.59). Using the QLQ-C30 Item 29 (n = 5) and 30 (n = 6) anchors, Physical Functioning scores worsened by -6.67 (Item 29 mean = -20.00; Item 30 mean = -24.44) for patients reporting deterioration on the anchor. For patients reported ‘no change’ on the EORTC QLQ-C30 Items 29 and 30 anchors, the upper 95% CI (indicating improvement) were 5.51 and 8.15, respectively, which support the threshold (primary TTI threshold = 8). In addition, patients with ‘improvement’ on the Items 29 and 30 anchors reported a median improvement of 6.67 in Physical Functioning scores, also supporting the TTI threshold.
EORTC QLQ-OG25 Pain and Discomfort
The half SD of EORTC QLQ-OG25 Pain and Discomfort at baseline were estimated at 13.64. Correlations between change in Pain and Discomfort and the anchor were sufficient (absolute value r > 0.37), except for PGIC-type Item 4 (r = 0.26). On the QLQ-C30 Items 29 and 30 anchors for QLQ-OG25 Pain, patients reported worsening with a mean QLQ-OG25 Pain score worsening of 13.33 and 16.67 points, respectively (both median change = 0.00). In addition, the upper 95% CI (indicating worsening) for QLQ-OG25 Pain scores among patients with ‘no change’ on the QLQ-C30 Items 29 and 30 anchors were 4.85 and 3.80, respectively (Item 29: n = 10; Item 30: n = 12) and half the baseline SD was 13.64, which support the threshold (time to deterioration [TTD] threshold = 16.7). For patients reported ‘improvement’ on the EORTC QLQ-C30 Items 29 and 30 anchors, the mean QLQ-OG25 Pain scores were -11.11 and -8.33, respectively (Item 29: n = 12; Item 30: n = 12) and half the baseline SD was 13.64 (TTI threshold = 16.67). However, the lower 95% CIs (indicating
improvement) for patients reporting ‘no change’ on the anchors were larger than the threshold (Upper 95% CI: Item 29 = -18.19; Item 30 = -33.43).
Conclusion
This Exit Survey report aimed on estimating within-patient meaningful change thresholds for measures of three areas of HRQoL, including EORTC QLQ-C30 GHS/QoL and Physical Functioning, and EORTC QLQ-OG25 Abdominal Pain and discomfort scores; however, the anchor-based estimates were not able to be recommended due to low sample size. The Exit Survey results supported the thresholds used in the SPOTLIGHT and GLOW clinical SAP TTD analyses (note derived from the phase 2 results; primary TTD thresholds for EORTC QLQ-C30 GHS/QoL and Physical Functioning: -10 [SPOTLIGHT] and -13 [GLOW]; EORTC QLQ-OG25 Abdominal Pain and discomfort: -16.67) and time to improvement (TTI) thresholds (EORTC QLQ-C30 GHS/QoL: +8; Physical Functioning:
+7; EORTC QLQ-OG25 Abdominal Pain and discomfort: +16.67), though it is important to note that these results should be cautiously interpreted. The 95% CIs among patients with no change on the anchor as well as the distribution-based results cautiously provide supportive evidence for the thresholds (EORTC QLQ-C30 GHS/QoL: no change and improvement; Physical Functioning: no change, worsening, and improvement; EORTC QLQ-OG25 Abdominal Pain and discomfort: no change and worsening) used in the SPOTLIGHT and GLOW clinical SAP analyses. Although anchor-based within-patient change thresholds for worsening could not be estimated, the half SD at baseline and 95% CIs for patients reporting no change were lower than the magnitude of thresholds used for deterioration (i.e., in the time to deterioration analyses).REC name
London - Riverside Research Ethics Committee
REC reference
22/PR/0879
Date of REC Opinion
29 Nov 2022
REC opinion
Further Information Favourable Opinion