Human Papilloma Virus (HPV) Circulating Tumor DNA (ctDNA) in Cervical Cancer
- Conditions
- Recurrent Cervical CarcinomaStage I Cervical Cancer FIGO 2018Stage IB1 Cervical Cancer AJCC v8Stage IIA1 Cervical Cancer FIGO 2018Stage IIA2 Cervical Cancer FIGO 2018Stage IIIA Cervical Cancer FIGO 2018Metastatic Cervical CarcinomaStage IA Cervical Cancer FIGO 2018Stage IA1 Cervical Cancer FIGO 2018Stage IA2 Cervical Cancer FIGO 2018
- Interventions
- Procedure: Biospecimen Collection
- Registration Number
- NCT04574635
- Lead Sponsor
- Mayo Clinic
- Brief Summary
This study collects blood samples to determine if the DNA of HPV that causes cervical cancer can be detected in patients with cervical cancer that is new (primary), has come back (recurrent), or has spread to other places in the body (metastatic) and are undergoing treatment with surgery, radiotherapy, chemotherapy, and/or immunotherapy. Researchers may use this information to predict response (good or bad) of the cervical cancer to treatment and detect recurrent cancer sooner.
- Detailed Description
PRIMARY OBJECTIVES:
I. To estimate the ctDNA detection rate in cervix cancer patients undergoing surgery, radiotherapy, chemotherapy, and/or immunotherapy in the setting of primary, recurrent or metastatic disease.
II. Association of ctDNA baseline levels and clearance kinetics with clinical and radiographic tumor response.
III. To explore the association of detectable ctDNA at each time point with invasive recurrence-free survival and overall survival.
IV. To explore the use of ctDNA for surveillance and detection of disease recurrence.
V. To create a repository for future exploratory studies including analyzing changes in T cell and other immune cell subpopulations during and following therapy for cervix cancer.
OUTLINE: Patients are assigned to 1 of 4 cohorts.
COHORT 1: Patients undergo collection of blood samples at baseline prior to surgery, at 6 weeks, 3, 6, and 12 months post-surgery, every 6 months during year 2, and at the time of recurrence (if applicable).
COHORT 2: Patients undergo collection of blood samples at baseline prior to the first fraction of radiation, during week 4 of radiotherapy, at 6 weeks, 3, 6, and 12 months post-radiotherapy, every 6 months during year 2, and at the time of recurrence (if applicable).
COHORT 3: Patients undergo collection of blood samples at baseline prior to the first fraction of radiation, during week 4 of radiotherapy, on the day of the final fraction of radiotherapy, at 3 months post-radiotherapy, every 3 months during years 1 and 2, and at the time of recurrence (if applicable).
COHORT 4: Patients undergo collection of blood samples at baseline prior to initiation of chemotherapy or immunotherapy, at 4 weeks and 8 weeks after initiation of chemotherapy or immunotherapy, every 3 months during years 1 and 2, and at the time of recurrence (if applicable).
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- Female
- Target Recruitment
- 60
-
Able to provide written consent
-
Patient has given permission to give tumor/blood sample for research testing
-
Histological confirmation of adenocarcinoma, adenosquamous, or small cell carcinoma of the cervix
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Known HPV status defined as positive staining for p16 on IHC or DNA ISH for HPV
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Willingness to return to enrolling institution (Mayo Clinic Rochester or the University of Minnesota) for follow-up (during the Active Monitoring Phase of the study) or complete blood draws locally using study mail-in kits
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Consent to allow blood specimens to be shared with Mayo Clinic study personnel and potential external collaborators for sample analysis
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Definitive Chemoradiotherapy for Locally Advanced Disease (FIGO Stage IB2-IIIC)
- FIGO 2019 Stage IB2-IIIC or not a surgical candidate
- Plan to undergo definitive chemoradiotherapy including external beam radiotherapy, brachytherapy, and chemotherapy
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Other active malignancy =< 2 years prior to registration.
- EXCEPTIONS: Non-melanotic skin cancer
- NOTE: If there is a history or prior malignancy, they must not be receiving other specific treatment for cancer
-
Pregnancy or lactation
-
Inability on the part of the patient to understand the informed consent to be compliant with the protocol
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Cohort 1 (surgery patients) Biospecimen Collection Patients undergo collection of blood samples at baseline prior to surgery, at 6 weeks, 3, 6, and 12 months post-surgery, every 6 months during year 2, and at the time of recurrence (if applicable). Cohort 2 (post-operative radiation +/- chemotherapy patients) Biospecimen Collection Patients undergo collection of blood samples at baseline prior to the first fraction of radiation, during week 4 of radiotherapy, at 6 weeks, 3, 6, and 12 months post-radiotherapy, every 6 months during year 2, and at the time of recurrence (if applicable). Cohort 3 (definitive chemoradiotherapy patients) Biospecimen Collection Patients undergo collection of blood samples at baseline prior to the first fraction of radiation, during week 4 of radiotherapy, on the day of the final fraction of radiotherapy, at 3 months post-radiotherapy, every 3 months during years 1 and 2, and at the time of recurrence (if applicable). Cohort 4 (systemic treatment patients) Biospecimen Collection Patients undergo collection of blood samples at baseline prior to initiation of chemotherapy or immunotherapy, at 4 weeks and 8 weeks after initiation of chemotherapy or immunotherapy, every 3 months during years 1 and 2, and at the time of recurrence (if applicable).
- Primary Outcome Measures
Name Time Method Proportion of patients with undetectable circulating tumor deoxyribonucleic acid (ctDNA) posttreatment in patients with detectable ctDNA pre-treatment At 6 weeks post-surgery (cohort 1), at 4-6 weeks after completion of chemotherapy and radiation (cohort 2), 4-6 weeks post End of chemotherapy and radiotherapy (cohort 3), at 8 weeks after start of chemotherapy or immunotherapy (cohort 4) The proportion will be reported along with the exact 95% binomial confidence interval. Additionally will report the mean standard deviation and median interquartile range ctDNA post-treatment in these patients.
- Secondary Outcome Measures
Name Time Method Clinical tumor response At post-treatment assessment, assessed up to 2 years Will be assessed for association with baseline and post-treatment ctDNA using logistic regression. Depending on the number of tumor response, or non-response patients whichever is fewer, multiple variable models may be considered including additional relevant baseline covariates such as disease stage.
Overall survival Up to 2 years Baseline ctDNA and ctDNA at measured time points will be considered in Cox models. ctDNA other than at baseline will be considered in these models as a time dependent covariate. Depending on the number of events, multiple variable models may be considered including additional relevant baseline covariates such as disease stage.
ctDNA clearance kinetics Up to 2 years Will be correlated with recurrence-free survival. ctDNA other than at baseline will be considered in these models as a time dependent covariate. Depending on the number of events, multiple variable models may be considered including additional relevant baseline covariates such as disease stage.
ctDNA levels Baseline Will be associated with Federation of Gynecology and Obstetrics stage and assessed using linear regression, reporting the correlation as well as the model estimates.
Radiographic tumor response At post-treatment assessment, assessed up to 2 years Will be assessed for association with baseline and post-treatment ctDNA using logistic regression. Depending on the number of tumor response, or non-response patients whichever is fewer, multiple variable models may be considered including additional relevant baseline covariates such as disease stage.
Recurrence-free survival Up to 2 years Baseline ctDNA and ctDNA at measured time points will be considered in Cox models.
ctDNA conversion Up to 2 years Will be correlated during the active monitoring phase with recurrence-free survival.
Trial Locations
- Locations (2)
University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
Mayo Clinic in Rochester
🇺🇸Rochester, Minnesota, United States