- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03491033
Genomic Profiling of the Residual Disease of Advanced-stage Ovarian Cancer After Neoadjuvant Chemotherapy
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
DNA extracted from FFPE block will be used. Capture sequencing and immunohistochemistry will be performed.
Immunohistochemistry The formalin-fixed, paraffin-embedded tissue blocks were sectioned at 4 µm thickness onto Superfrost Plus glass slides (Thermo Fisher Scientific, Waltham, MA, USA). These sections were deparaffinized in xylene and rehydrated through graded alcohols. Immunohistochemical staining was performed using an automatic immunostaining instrument (Ventana Benchmark XT; Ventana Medical Systems), according to the manufacturer's recommendations. Antigen retrieval was performed using a Cell Conditioning Solution (CC1; Ventana Medical Systems). The sections were incubated with antibodies against PD-L1 (prediluted, clone SP263, Ventana Medical Systems), CD8 (prediluted, clone C8/144B, Dako, Glostrup, Denmark), PD-1 (1:50, clone NAT105, Cell Marque, Rocklin, CA, USA), Foxp3 (1:50, clone 236A/E7, Abcam, Cambridge, UK), ICOS/CD278 (1:50, clone SP98, Thermo Fisher Scientific), and LAG-3 (1:100, clone EPR4392(2), Abcam). After chromogenic visualization using an ultraView Universal DAB Detection Kit (Ventana Medical Systems), the slices were counterstained with hematoxylin, dehydrated in graded alcohols and xylene, and then embedded in mounting solution. Appropriate positive and negative controls were concurrently stained to validate the staining method.
Targeted Capture Sequencing on NextSeq550 using SureSelect XT Sample Preparation DNA was extracted from microdissected tumor rich areas from formalin fixed paraffin embedded tumor sections using DNAeasy kit (QIAGEN, Venlo, Netherlands). Two hundred fifty nanogram of genomic DNA in 50μl TE buffer was fragmented to a median size of 150bp using the Covaris-E220 AFA instrument (Covaris, Woburn, MA) with the following settings: peak incident power 175 watts, duty factor 10.0%, cycles per burst 200 cycles, run time 500 sec at 4oC. DNA fragments were evaluated using capillary electrophoresis on High Sensitivity D1000 ScreenTape and Reagents (TapeSation4200, Cat.No.5067-5584, 5585; Agilent Technologies, Santa Clara, CA, USA). End repair, 3'-end adenylation and sequencing adapter ligation of DNA fragments were performed following the manufacture's protocol (SureSelect XT Reagent kit, HSQ Cat.No.G9611A, G9611B; Agilent Technologies, Santa Clara, CA, USA). After each steps, fragments were purified using AMPure XP beads (Cat. No. A63382; Beckman Coulter, High Wycombe, UK). The resulting DNA was amplified by 14 cycles PCR amplification (SureSelect Herculase Ⅱ Fusion Enzyme with dNTP Combo 200 RXN kit, Cat. No. 600677; Agilent Technologies, Santa Clara, CA, USA). The quality of the PCR product was assessed by capillary electrophoresis with DNA1000 TapeScreen and Reagents (TapeSation4200, Cat.No.5067-5582, 5583; Agilent Technologies, Santa Clara, CA, USA) and the concentration was measured by Qubit 2.0 Fluorometer (Qubit dsDNA HS Assay Kit, Cat. No. Q32854; Thermofisher Scientific, Inc, Waltham, MA).
Capture and Enrichment Target enrichment was performed according to the manufacturer's instructions (SureSelect XT Custom 0.5Mb-2.9Mb library, Cat. No. 5190-4816, 4817; Agilent Technologies, Santa Clara, CA, USA). The resulting captured libraries with indexing primers were amplified by 12 cycles of PCR (SureSelect Herculase Ⅱ Fusion Enzyme with dNTP Combo 200 RXN kit, Cat. No. 600677; Agilent Technologies, Santa Clara, CA, USA) and purified again. Quantity and quality of indexed library DNA were verified by capillary electrophoresis with High Sensitivity D1000 ScreenTape and Reagents (TapeSation4200, Cat.No.5067-5584, 5585; Agilent Technologies, Santa Clara, CA, USA) and Qubit 2.0 Fluorometer (Qubit dsDNA HS Assay Kit, Cat. No. Q32854; Thermofisher Scientific, Inc, Waltham, MA).
Sequencing We diluted resulting libraries to 4nmol/l and pooled by combining 5μl of each diluted library for normalization. Subsequently, pooled library was denatured into single strands by using fresh 0.2N NaOH and 200mM Tris-HCl, pH7. A PhiX control was denatured in the same way. The concentration of final loading library was 1.8pmol/l and Phix was spiked in at 1%. A standard flow cell was loaded on the Illumina NextSeq550 and sequencing was conducted with 2X100bp paired-end reads using NextSeq550 reagent v2 kit with high-output 300 cycles. (NextSeq550 System user guide part #15069765-V02 Mar 2016, NextSeq550 Reagent V2 Kit High-output 300 cycles Cat. No. FC-404-2004; Illumina, CA).
Study Type
Enrollment (Actual)
Contacts and Locations
Study Locations
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Seoul, Korea, Republic of, 03722
- Severance Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
Inclusion Criteria:
- patients with pathologically confirmed epithelial ovarian cancer who received at least 1 cycle of neoadjuvant chemotherapy
- The patient inclusion criteria included 1) high grade serous carcinoma 2) stage III/IV disease 3) availability of clinical data and tumor tissue 4) viable residual tumors after neoadjuvant chemotherapy.
Exclusion Criteria:
- patients with complete pathologic response (CRS 3) as IHC staining was insufficient or unavailable
Study Plan
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
advanced-stage ovarian cancer group
250 patients with pathologically confirmed epithelial ovarian cancer who received at least 1 cycle of NAC at Yonsei Cancer Hospital from 2006 to 2017.
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All of the patients in this study underwent NAC regimens consisting of taxane and platinum combination chemotherapy.
After NAC, all of the patients underwent interval debulking surgery.
Subsequently, additional cycles of chemotherapy were administered after IDS to complete a total of 6 cycles at the discretion of the treating physician.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
genomic profiling
Time Frame: 3 months
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demonstrates the spectrum of genomic alterations/ profiling present in residual disease after neoadjuvant chemotherapy.
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3 months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
immunohistochemistry
Time Frame: 3 months
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To evaluate the prognostic significance of BRCA-1 IHC in residual disease after neoadjuvant chemotherapy in ovarian cancer
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3 months
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Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Urogenital Neoplasms
- Neoplasms by Site
- Carcinoma
- Neoplasms, Glandular and Epithelial
- Genital Neoplasms, Female
- Endocrine System Diseases
- Ovarian Diseases
- Adnexal Diseases
- Gonadal Disorders
- Endocrine Gland Neoplasms
- Ovarian Neoplasms
- Carcinoma, Ovarian Epithelial
Other Study ID Numbers
- 4-2017-0632
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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