Ignite Creation Date:
2024-05-06 @ 8:11 PM
Last Modification Date:
2024-10-26 @ 3:22 PM
Study NCT ID:
NCT06283238
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-05-23
First Post:
2024-02-22
Brief Title:
Biobanking Upper Gastrointestinal Tumors to Evaluate Response BURGER With BACON
Sponsor:
Duke University
Organization:
Duke University
Study Overview
Official Title:
Biobanking Upper Gastrointestinal Tumors to Evaluate Response With Additional Banking of Cutaneous Neoplasms BURGER With BACON
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-02
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:
The goal of this observational study is to examine genetic changes that may contribute to immunotherapy resistance in gastroesophageal cancer This information can potentially lead to the identification of new immunotherapeutic targets as well as improve the ability to identify those patients more likely to respond to immunotherapy
This study does not include any treatment or investigational drugs
Participants will be asked
to enroll before beginning standard care of treatment for their cancer
for blood archived tumor tissue and fresh tumor tissue Researchers will compare participants who are not getting immunotherapy to identify potential differences in expression levels of a gene
This study does not include any treatment or investigational drugs
Participants will be asked
to enroll before beginning standard care of treatment for their cancer
for blood archived tumor tissue and fresh tumor tissue Researchers will compare participants who are not getting immunotherapy to identify potential differences in expression levels of a gene
Detailed Description:
The study will be divided into three cohorts 1 Cohort A which will enroll subjects prior to treatment with an immune checkpoint inhibitor or chemotherapy alone 2 Cohort B which will analyze samples collected from melanoma patients under Pro00059349 and 3 Cohort C a retrospective portion that will allow for collection of data and archived tissue
Cohort A GE Subjects Treated with ICI
Participating subjects will be enrolled prior to initiating treatment with a regimen that includes an immune checkpoint inhibitor or chemotherapy alone in the case of the immunotherapy ineligible cohort Archived formalin fixed paraffin embedded FFPE tumor tissue will be collected for all subjects if available Patients will have an optional fresh research only biopsy if there is a lesion amenable to safe biopsy which will be frozen for further studies Additionally excess tissue may be collected and flash frozen from standard of care biopsies that occur while patient is on study Objective response assessments for these patients will be made by MD assessment based on standard-of-care CT or MRI cross-sectional imaging Blood andor tissue specimens will be taken accordingly at the following time points
Baseline pre-treatment
Patients will undergo a research blood draw If subject receives a standard of care biopsy after consenting but before starting anti-PD-1 therapy every attempt will be made to collect tissue from this biopsy for research purposes If the patient is not scheduled for standard of care biopsy during this period they will only undergo blood draw
During Treatment
Patients will undergo an optional research tissue biopsy and a research blood draw while on anti-PD-1 therapy treatment at the time of their first restaging scan Patient will undergo another research blood draw while on anti-PD-1 therapy at the time of their second restaging scan Lesions that were biopsied previously will be prioritized for on treatment biopsy Any tissue that has been subjected to radiation therapy will not be considered for sampling Those patients that have evidence of stable disease or response may undergo a repeat blood draw at time points beyond the second staging scan at PI discretion If patients remain on anti-PD-1 therapy for more than 12 months the PI may request additional blood draws after 12 months on treatment
After Treatment
At the time of anti-PD-1 therapy discontinuation due to toxicity or disease progression patient will undergo a blood draw If the patient has a standard of care biopsy at progression excess tissue from this biopsy will be obtained for research
Sample acquisition processing and storage
Archived formalin fixed paraffin embedded FFPE tumor tissue will be collected for all subjects if available Available tissue blocks will be assessed and up to 40 slides will be collected for IHC DNA and RNA extraction On-treatment tumor biopsies will be performed only on patients who have a tumor lesion that is amenable to safe biopsy and will be flash frozen Frozen specimens will be processed for whole tumor RNA and subsequent transcriptional analysis Those archived tissue specimens identified as being located at outside institutions will be requested by the study team and stored in the Hanks lab Tumor tissue slides will require pathologic review by a board-certified pathologist and an estimated minimum 10 of tumor tissue per slide will be confirmed
Use of any tissue blocks that would result in the exhaustion of available tissue will be avoided unless the patient is confirmed to be no longer living
Patient specimens containing whole blood will be collected and processed within the Duke Cancer Center Research Lab CCRL Four 10 mL EDTA tubes will be used for double spun platelet poor plasma and peripheral blood mononuclear cells PBMC All four 10 mL EDTA tube will be used for buffy coat isolation The buffy coat collected during this preparation for genomic DNA isolation will be transported and stored at -80C in the Hanks Laboratory LSRC C164-167 for future genomic DNA sequencing studies Plasma will be isolated and stored at -80C in the Hanks Laboratory for subsequent multi-analyte ELISA studies ctDNA analysis ctRNA analysis andor exosome isolation and analysis Three 85mL ACD tubes will be used for PBMCs These will be processed and stored by the Substrate Services Core and Research Support SSCRS PBMCs will be analyzed by the Duke Immune Profiling Core facility under the direction of Dr Kent Weinhold
Proposed Research
1 Up to 70 patients will be enrolled in Cohort A
2 Blood specimens may be investigated for
1 Plasma-EDTA samples may be sent to an external collaborator for genomic profiling of circulating tumor DNA Alternative CLIA-certified circulating tumor DNA assays can be considered
2 Circulating protein biomarkers for immune function inflammation angiogenesis and vascular activation will be analyzed by multiplex ELISA assays
3 PBMC samples will be analyzed for immune cell subtyping using high dimensional flow cytometry in the Duke Immune Profiling Core DIPC laboratory A 28-parameter flow cytometry panels will be used to analyze changes in the immune cell subtypes that are expected to be altered by treatment including T-cell activation maturation and exhaustion as well as regulatory T-cell Treg and polymorphonuclear myeloid-derived suppressor cells PMN-MDSC frequencies
3 Blood-based analytes between responders and non-responders will be compared Due to the small sample size results will be descriptive
4 Clinical and demographic data Cohorts A and C will be extracted from the medical record for each subject including but not limited to the following
1 Age
2 Gender
3 Race
4 Zip Code
5 Number of prior therapies
6 Clinical outcomes from standard and investigational therapies best response duration of response and reason for discontinuation
7 Clinical outcomes from immune checkpoint inhibitor therapies best response duration of response and reason for discontinuation
8 Results of blood-based and tissue-based profiling studies
9 Molecular markers that may predict sensitivity or resistance to anti-PD-1 therapy including but not limited to tumor mutational burden PD-L1 MSI status POLE STATUS
5 Tissue specimens Cohorts A and C may be acquired from outside hospitals in cases where patients enrolled under this protocol have had biopsies performed and stored at hospitals outside of the Duke Health hospital system prior to transitioning care to Duke
6 Fresh frozen tissue specimens Cohort A only will be extracted for RNA and downstream transcriptional analysis will be performed Available tissue blocks will be assessed and up to 40 slides will be collected for RNA extraction and further downstream processing to determine bulk tumor transcriptome when fresh tissue is not available
Cohort B Melanoma Subjects Treated with ICI
Samples collected under Pro00059349 came from subjects in the following groups
1 Arm 1 - stage IV unresectable stage III melanoma patients who enrolled prior to starting immunotherapy
2 Arm 2 - Stage IIIIV adjuvant melanoma patients
Subjects in both arms had and may continue to have data collected from their medical records Information was collected under Pro00059349 and may continue to be monitored under this protocol
Cohort C Retrospective Identification and Collection of Archived Tissue The DEDUCE Duke Enterprise Data Unified Content Explorer software tool will be utilized to identify patients with gastroesophageal adenocarcinoma or squamous cell or melanoma initiated on anti-PD-1 antibody immunotherapy at Duke University Medical Center and the Duke Cancer Institute between January 1 2011 and August 31 2023 and patients ineligible for immunotherapy that received chemotherapy during the same time period Anti-PD-1 antibody therapies will include pembrolizumab nivolumab or another checkpoint inhibitor Patients must be 18 years old at the time of initiating treatment Objective response assessments for these patients will be made based on standard-of-care week 12 CT or PET CT cross-sectional imaging Additional corresponding medical history will be collected and databased for these patients This includes but is not limited to demographics disease primary and metastatic sites prior medical conditions and cancer treatment Tissue blocks and medical history will be obtained according to a Waiver of Consent for this retrospective component only as the collection represents a minimal risk activity and it is not feasible to consent patients that were identified retrospectively Archived tissue collection will be the same as for Cohort A
Screening Period During the Screening Period subjects are consented and screened for the study Informed consent must be obtained before initiation of any screening procedure that is performed solely for the purpose of determining eligibility for this study Evaluations performed as part of routine care before informed consent can be considered as screening evaluations if done within the defined screening period and if permitted by the local Institutional Review Board IRB Independent Ethics Committee IEC policies Study eligibility is based on meeting all of the inclusion criteria and none of the exclusion criteria refer to section 40 before the blood draws andor biopsies are performed
The following study procedures must be done within 28 days prior to blood draw andor biopsy
Informed Consent
Demographics
Medical and cancer history
Concomitant medications
Excess tissue collection from standard of care biopsy if applicable safe and feasible The Screening Period ends at the time of the blood draw or biopsy or final determination that the subject is ineligible for the study
511 On Study Period
Prior to starting checkpoint inhibitor or chemotherapy
Blood draws
Approximately 40 cc total in 4 x 10 mL EDTA tubes
Approximately 255 cc total in 3 x 85 mL ACD tubes
Within - 7 days of 1st and 2nd restaging
o Blood draws
Approximately 40 cc total in 4 x 10 mL EDTA tubes
Approximately 255 cc total in 3 x 85 mL ACD tubes
Optional tumor biopsy 1st restaging only
PTINR prior to biopsy 1st restaging only
CBC prior to biopsy 1st restaging only
Within - 7 days of additional restaging visits at PI request
o Blood draws
Approximately 40 cc total in 4 x 10 mL EDTA tubes
Approximately 255 cc total in 3 x 85 mL ACD tubes
Anytime while on treatment
o If the patient has a standard of care biopsy at any time while on treatment excess tissue from this biopsy will be obtained for research if safe and feasible
o Clinical data will be extracted from the medical record per section 30 for each subject up until 3 months after completion of a line of checkpoint inhibitor therapy or chemotherapy while on study
Within - 7 days of discontinuing anti-PD-1 therapy for toxicity or progression o Blood draws - Approximately 40 cc total in 4 x 10 mL EDTA tubes
Approximately 255 cc total in 3 x 85 mL ACD tubes o If the patient has a standard of care biopsy at progression excess tissue from this biopsy will be obtained for research
If patient discontinues immunotherapy for complete response CR blood draws will occur at time of discontinuation and during 2 subsequent SOC re-staging visits or until progression whichever comes first
End of study
If available archived FFPE tissue will be obtained from all subjects at the end of the study
Cohort B Sample collection for cohort B was completed under Pro00059349 Analysis is ongoing and will continue under this protocol There will be no new subjects enrolled to cohort B nor any new samples collected from these subjects However data will continue to be collected from their electronic medical records
Cohort C Subjects for the retrospective cohort will be identified as described above The investigators will enroll these subjects under a waiver of consent collect the data listed in section 30 and obtain archived tissue There will be no separate screening or fup periods for these subjects
Subject Discontinuation
Subjects will continue to be followed until they complete immune checkpoint inhibitor treatment and the final blood and tissue samples are collected However subjects may discontinue study treatment or withdraw their consent to participate in the study at any time without prejudice Any subject who withdraws consent for Pro0059349 will also have their samples and data withdrawn from this study All reasons for discontinuation or withdrawal from trial will be recorded Reasons for subject discontinuation by the Investigator may include but are not limited to the following
Death
Significant noncompliance by subject or Investigator
Investigator or Lead PI determination that it is no longer safe andor no longer in the subjects best interest to continue participation
Withdrawal of consent
Lost to follow-up
Women who become pregnant or are breast feeding
Request by regulatory agencies for termination of treatment of an individual subject or all subjects under the protocol
Cohort A GE Subjects Treated with ICI
Participating subjects will be enrolled prior to initiating treatment with a regimen that includes an immune checkpoint inhibitor or chemotherapy alone in the case of the immunotherapy ineligible cohort Archived formalin fixed paraffin embedded FFPE tumor tissue will be collected for all subjects if available Patients will have an optional fresh research only biopsy if there is a lesion amenable to safe biopsy which will be frozen for further studies Additionally excess tissue may be collected and flash frozen from standard of care biopsies that occur while patient is on study Objective response assessments for these patients will be made by MD assessment based on standard-of-care CT or MRI cross-sectional imaging Blood andor tissue specimens will be taken accordingly at the following time points
Baseline pre-treatment
Patients will undergo a research blood draw If subject receives a standard of care biopsy after consenting but before starting anti-PD-1 therapy every attempt will be made to collect tissue from this biopsy for research purposes If the patient is not scheduled for standard of care biopsy during this period they will only undergo blood draw
During Treatment
Patients will undergo an optional research tissue biopsy and a research blood draw while on anti-PD-1 therapy treatment at the time of their first restaging scan Patient will undergo another research blood draw while on anti-PD-1 therapy at the time of their second restaging scan Lesions that were biopsied previously will be prioritized for on treatment biopsy Any tissue that has been subjected to radiation therapy will not be considered for sampling Those patients that have evidence of stable disease or response may undergo a repeat blood draw at time points beyond the second staging scan at PI discretion If patients remain on anti-PD-1 therapy for more than 12 months the PI may request additional blood draws after 12 months on treatment
After Treatment
At the time of anti-PD-1 therapy discontinuation due to toxicity or disease progression patient will undergo a blood draw If the patient has a standard of care biopsy at progression excess tissue from this biopsy will be obtained for research
Sample acquisition processing and storage
Archived formalin fixed paraffin embedded FFPE tumor tissue will be collected for all subjects if available Available tissue blocks will be assessed and up to 40 slides will be collected for IHC DNA and RNA extraction On-treatment tumor biopsies will be performed only on patients who have a tumor lesion that is amenable to safe biopsy and will be flash frozen Frozen specimens will be processed for whole tumor RNA and subsequent transcriptional analysis Those archived tissue specimens identified as being located at outside institutions will be requested by the study team and stored in the Hanks lab Tumor tissue slides will require pathologic review by a board-certified pathologist and an estimated minimum 10 of tumor tissue per slide will be confirmed
Use of any tissue blocks that would result in the exhaustion of available tissue will be avoided unless the patient is confirmed to be no longer living
Patient specimens containing whole blood will be collected and processed within the Duke Cancer Center Research Lab CCRL Four 10 mL EDTA tubes will be used for double spun platelet poor plasma and peripheral blood mononuclear cells PBMC All four 10 mL EDTA tube will be used for buffy coat isolation The buffy coat collected during this preparation for genomic DNA isolation will be transported and stored at -80C in the Hanks Laboratory LSRC C164-167 for future genomic DNA sequencing studies Plasma will be isolated and stored at -80C in the Hanks Laboratory for subsequent multi-analyte ELISA studies ctDNA analysis ctRNA analysis andor exosome isolation and analysis Three 85mL ACD tubes will be used for PBMCs These will be processed and stored by the Substrate Services Core and Research Support SSCRS PBMCs will be analyzed by the Duke Immune Profiling Core facility under the direction of Dr Kent Weinhold
Proposed Research
1 Up to 70 patients will be enrolled in Cohort A
2 Blood specimens may be investigated for
1 Plasma-EDTA samples may be sent to an external collaborator for genomic profiling of circulating tumor DNA Alternative CLIA-certified circulating tumor DNA assays can be considered
2 Circulating protein biomarkers for immune function inflammation angiogenesis and vascular activation will be analyzed by multiplex ELISA assays
3 PBMC samples will be analyzed for immune cell subtyping using high dimensional flow cytometry in the Duke Immune Profiling Core DIPC laboratory A 28-parameter flow cytometry panels will be used to analyze changes in the immune cell subtypes that are expected to be altered by treatment including T-cell activation maturation and exhaustion as well as regulatory T-cell Treg and polymorphonuclear myeloid-derived suppressor cells PMN-MDSC frequencies
3 Blood-based analytes between responders and non-responders will be compared Due to the small sample size results will be descriptive
4 Clinical and demographic data Cohorts A and C will be extracted from the medical record for each subject including but not limited to the following
1 Age
2 Gender
3 Race
4 Zip Code
5 Number of prior therapies
6 Clinical outcomes from standard and investigational therapies best response duration of response and reason for discontinuation
7 Clinical outcomes from immune checkpoint inhibitor therapies best response duration of response and reason for discontinuation
8 Results of blood-based and tissue-based profiling studies
9 Molecular markers that may predict sensitivity or resistance to anti-PD-1 therapy including but not limited to tumor mutational burden PD-L1 MSI status POLE STATUS
5 Tissue specimens Cohorts A and C may be acquired from outside hospitals in cases where patients enrolled under this protocol have had biopsies performed and stored at hospitals outside of the Duke Health hospital system prior to transitioning care to Duke
6 Fresh frozen tissue specimens Cohort A only will be extracted for RNA and downstream transcriptional analysis will be performed Available tissue blocks will be assessed and up to 40 slides will be collected for RNA extraction and further downstream processing to determine bulk tumor transcriptome when fresh tissue is not available
Cohort B Melanoma Subjects Treated with ICI
Samples collected under Pro00059349 came from subjects in the following groups
1 Arm 1 - stage IV unresectable stage III melanoma patients who enrolled prior to starting immunotherapy
2 Arm 2 - Stage IIIIV adjuvant melanoma patients
Subjects in both arms had and may continue to have data collected from their medical records Information was collected under Pro00059349 and may continue to be monitored under this protocol
Cohort C Retrospective Identification and Collection of Archived Tissue The DEDUCE Duke Enterprise Data Unified Content Explorer software tool will be utilized to identify patients with gastroesophageal adenocarcinoma or squamous cell or melanoma initiated on anti-PD-1 antibody immunotherapy at Duke University Medical Center and the Duke Cancer Institute between January 1 2011 and August 31 2023 and patients ineligible for immunotherapy that received chemotherapy during the same time period Anti-PD-1 antibody therapies will include pembrolizumab nivolumab or another checkpoint inhibitor Patients must be 18 years old at the time of initiating treatment Objective response assessments for these patients will be made based on standard-of-care week 12 CT or PET CT cross-sectional imaging Additional corresponding medical history will be collected and databased for these patients This includes but is not limited to demographics disease primary and metastatic sites prior medical conditions and cancer treatment Tissue blocks and medical history will be obtained according to a Waiver of Consent for this retrospective component only as the collection represents a minimal risk activity and it is not feasible to consent patients that were identified retrospectively Archived tissue collection will be the same as for Cohort A
Screening Period During the Screening Period subjects are consented and screened for the study Informed consent must be obtained before initiation of any screening procedure that is performed solely for the purpose of determining eligibility for this study Evaluations performed as part of routine care before informed consent can be considered as screening evaluations if done within the defined screening period and if permitted by the local Institutional Review Board IRB Independent Ethics Committee IEC policies Study eligibility is based on meeting all of the inclusion criteria and none of the exclusion criteria refer to section 40 before the blood draws andor biopsies are performed
The following study procedures must be done within 28 days prior to blood draw andor biopsy
Informed Consent
Demographics
Medical and cancer history
Concomitant medications
Excess tissue collection from standard of care biopsy if applicable safe and feasible The Screening Period ends at the time of the blood draw or biopsy or final determination that the subject is ineligible for the study
511 On Study Period
Prior to starting checkpoint inhibitor or chemotherapy
Blood draws
Approximately 40 cc total in 4 x 10 mL EDTA tubes
Approximately 255 cc total in 3 x 85 mL ACD tubes
Within - 7 days of 1st and 2nd restaging
o Blood draws
Approximately 40 cc total in 4 x 10 mL EDTA tubes
Approximately 255 cc total in 3 x 85 mL ACD tubes
Optional tumor biopsy 1st restaging only
PTINR prior to biopsy 1st restaging only
CBC prior to biopsy 1st restaging only
Within - 7 days of additional restaging visits at PI request
o Blood draws
Approximately 40 cc total in 4 x 10 mL EDTA tubes
Approximately 255 cc total in 3 x 85 mL ACD tubes
Anytime while on treatment
o If the patient has a standard of care biopsy at any time while on treatment excess tissue from this biopsy will be obtained for research if safe and feasible
o Clinical data will be extracted from the medical record per section 30 for each subject up until 3 months after completion of a line of checkpoint inhibitor therapy or chemotherapy while on study
Within - 7 days of discontinuing anti-PD-1 therapy for toxicity or progression o Blood draws - Approximately 40 cc total in 4 x 10 mL EDTA tubes
Approximately 255 cc total in 3 x 85 mL ACD tubes o If the patient has a standard of care biopsy at progression excess tissue from this biopsy will be obtained for research
If patient discontinues immunotherapy for complete response CR blood draws will occur at time of discontinuation and during 2 subsequent SOC re-staging visits or until progression whichever comes first
End of study
If available archived FFPE tissue will be obtained from all subjects at the end of the study
Cohort B Sample collection for cohort B was completed under Pro00059349 Analysis is ongoing and will continue under this protocol There will be no new subjects enrolled to cohort B nor any new samples collected from these subjects However data will continue to be collected from their electronic medical records
Cohort C Subjects for the retrospective cohort will be identified as described above The investigators will enroll these subjects under a waiver of consent collect the data listed in section 30 and obtain archived tissue There will be no separate screening or fup periods for these subjects
Subject Discontinuation
Subjects will continue to be followed until they complete immune checkpoint inhibitor treatment and the final blood and tissue samples are collected However subjects may discontinue study treatment or withdraw their consent to participate in the study at any time without prejudice Any subject who withdraws consent for Pro0059349 will also have their samples and data withdrawn from this study All reasons for discontinuation or withdrawal from trial will be recorded Reasons for subject discontinuation by the Investigator may include but are not limited to the following
Death
Significant noncompliance by subject or Investigator
Investigator or Lead PI determination that it is no longer safe andor no longer in the subjects best interest to continue participation
Withdrawal of consent
Lost to follow-up
Women who become pregnant or are breast feeding
Request by regulatory agencies for termination of treatment of an individual subject or all subjects under the protocol
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