Jian Li
Beijing, Beijing Municipality, 100142, China
Location status: Recruiting
Recruiting
NCT Number: NCT06549907
A Biomarker Exploratory Study of Dual Blockade of PD1/PDL1 and CTLA4 and Anti-angiogenic Therapy
This study is a single-center prospective exploratory research, aiming to identify clinical characteristics and biomarkers associated with the therapeutic effects of dual PD1/PDL1 and CTLA4 blockade plus anti-angiogenic therapy and investigate MR image characteristics during treatment in patients with MSS metastatic colorectal cancer and MSI solid tumors resistant to PD-1/PD-L1 antibody monotherapy.
Recruiting
Interested in participating?
Request InfoKey information
Conditions
Age range
18 year and older
Sex eligibility
All sexes
Study type
Observational
Primary location
About this study
This study is a single-center prospective exploratory research. Patients with MSS metastatic colorectal cancer and MSI solid tumors resistant to PD-1/PD-L1 antibody monotherapy who are treated with dual PD1/PDL1 and CTLA4 blockade combined with anti-angiogenic therapy in the Department of Gastrointestinal Oncology of Peking University Cancer Hospital will be enrolled. Their clinical-pathological features and specimens will be collected at baseline, at each tumor assessment point, and at disease progression.
This study aims to identify clinical characteristics and biomarkers associated with the therapeutic effects through multi-omics approaches, and to investigate MR image characteristics during treatment. Samples include tissue, blood, urine and stool, and multi-omics approaches include single-cell sequencing, spatial transcriptome sequencing, macro transcriptome sequencing, whole exome sequencing, microproteomics, immunohistochemistry, and multiplex fluorescence immunohistochemistry.
Who can participate
Healthy volunteers accepted: No
Only the study team can determine whether someone qualifies for participation.
Inclusion criteria
- Pathologically confirmed MSS metastatic colorectal cancers or MSI solid tumors refractory to PD1/PDL1 antibody monotherapy
- Receiving dual blockade of PD1/PDL1 and CTLA4 in combination of anti-angiogenic treatment with or without other therapies
Exclusion criteria
●Having malignancies in non-gastrointestinal system that have not been cured (Lynch syndrome not included)
Treatment and study plan
Multi-omics testing
OtherSamples include tissue, blood, urine and stool, and multi-omics approaches include single-cell sequencing, spatial transcriptome sequencing, macro transcriptome sequencing, whole exome sequencing, microproteomics, immunohistochemistry, and multiplex fluorescence immunohistochemistry.
MRI
OtherMRI will be conducted to investigate image characteristics during treatment
Primary outcomes
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Baseline proportion and location of different immune cell subsets associated with efficacy
Time frame: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose
Proportion and location of different immune cell subsets will be assessed by single-cell sequencing, spatial transcriptome sequencing, immunohistochemistry, and multiplex fluorescence immunohistochemistry using pre-treatment samples.
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Baseline tumor gene alterations associated with efficacy
Time frame: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose
Baseline tumor gene alterations will be assessed by whole exome sequencing using pre-treatment tissue or blood samples
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Baseline clinical characteristics associated with efficacy
Time frame: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose
Baseline clinical characteristics include age of onset, gender, family history, pathological type of tumor, primary tumor site, metastatic site, tumor size, and previous treatment.
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Baseline tumor-associated proteins associated with efficacy
Time frame: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose
Tumor-associated proteins will be assessed by microproteomics using pre-treatment blood or urine samples.
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Baseline intestinal flora associated with efficacy
Time frame: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose
Intestinal flora will be assessed by macro transcriptome sequencing using pre-treatment stool samples.
Secondary outcomes
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Early changes (within 8 weeks) of proportion and location of different immune cell subsets after treatment associated with efficacy
Time frame: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose
Proportion and location of different immune cell subsets will be assessed by single-cell sequencing, spatial transcriptome sequencing, immunohistochemistry, and multiplex fluorescence immunohistochemistry using pre-and post-treatment samples.
-
Early changes (within 8 weeks) of tumor gene alterations after treatment
Time frame: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose
Baseline tumor gene alterations will be assessed by whole exome sequencing using pre-and post-treatment tissue or blood samples.
-
Early changes (within 8 weeks) of tumor-associated proteins after treatment associated with efficacy
Time frame: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose
Tumor-associated proteins will be assessed by microproteomics using pre-and post treatment blood or urine samples.
-
Early changes (within 8 weeks) of intestinal flora after treatment associated with efficacy
Time frame: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose
Intestinal flora will be assessed by macro transcriptome sequencing using pre- and post-treatment stool samples.
-
Longitudinal on-treatment changes of proportion and location of different immune cell subsets at baseline, tumor shrinkage and progression
Time frame: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose
Proportion and location of different immune cell subsets will be assessed by single-cell sequencing, spatial transcriptome sequencing, immunohistochemistry, and multiplex fluorescence immunohistochemistry using pre-and post-treatment samples.
-
MR image characteristics
Time frame: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose
MR image characteristics at baseline and their changes when tumor responded or progressed
Study contacts
Contact information is provided by the study sponsor or research team.
Sponsors and collaborators
Lead sponsor
Peking University Cancer Hospital & Institute
Other
Registry information
Official study title
A Biomarker Exploratory Study of Efficacy and Prognosis of Dual Blockade of PD1/PDL1 and CTLA4 in Combination of Anti-angiogenic Treatment in MSS Metastatic Colorectal Cancers and MSI Solid Tumors Refractory to PD1/PDL1 Antibody Monotherapy
Important dates
- Study start
- 2024
- Primary completion
- 2028
- Study completion
- 2028
- First posted
- Aug 12, 2024
- Registry last updated
- Aug 12, 2024
OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.
View the official ClinicalTrials.gov record (opens in a new tab)This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.