Human Papilloma Virus (HPV) Circulating Tumor DNA (ctDNA) in Cervical Cancer

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.

Study Overview

• Status: Recruiting
• Conditions: Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Recurrent Cervical Carcinoma; Stage IB3 Cervical Cancer FIGO 2018; Stage II Cervical Cancer FIGO 2018; Stage IIA Cervical Cancer FIGO 2018; Stage IIA1 Cervical Cancer FIGO 2018; Stage IIA2 Cervical Cancer FIGO 2018; Stage IIB Cervical Cancer FIGO 2018; Stage III Cervical Cancer FIGO 2018; Stage IIIA Cervical Cancer FIGO 2018; Stage IIIB Cervical Cancer FIGO 2018; Stage IIIC Cervical Cancer FIGO 2018; Stage IIIC1 Cervical Cancer FIGO 2018; Stage IIIC2 Cervical Cancer FIGO 2018; Stage IVA Cervical Cancer FIGO 2018; Stage IB1 Cervical Cancer AJCC v8; Metastatic Cervical Carcinoma; Infiltrating Cervical Carcinoma; Stage I Cervical Cancer FIGO 2018; Stage IA Cervical Cancer FIGO 2018; Stage IA1 Cervical Cancer FIGO 2018; Stage IA2 Cervical Cancer FIGO 2018; Stage IB Cervical Cancer FIGO 2018; Stage IB2 Cervical Cancer FIGO 2018; Stage IV Cervical Cancer FIGO 2018; Stage IVB Cervical Cancer FIGO 2018
• Intervention / Treatment: Procedure: Biospecimen Collection

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).

• Study Type: Observational
• Enrollment (Estimated): 60

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic in Rochester
      • Contact: Clinical Trials Referral Office; Phone Number: 855-776-0015; Email: mayocliniccancerstudies@mayo.edu
      • Principal Investigator: Allison E. Garda, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients presenting with p16-positive or HPV-positive invasive carcinoma (including but not limited to squamous cell carcinoma, or adenocarcinoma, small cell carcinoma) of the cervix including primary, recurrent or metastatic disease

Description

Inclusion Criteria:

• Able to provide written consent
• Patient has given permission to give tumor/blood sample for research testing
• Histological confirmation of squamous cell carcinoma or adenosquamous carcinoma
• Known HPV status defined as positive staining for p16 on immunohistochemistry (IHC) or DNA in situ hybridization (ISH) for HPV
• Willingness to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study)
• Consent to allow blood specimens to be shared with potential external collaborators

• Cohort #1: Surgery alone for early stage disease (Federation of Gynecology and Obstetrics [FIGO] stage IA-IB1)

  • FIGO 2019 stage IA1, IA2, IB1
  • Plan to undergo surgery including but not limited to trachelectomy, radical hysterectomy, and lymph node dissection

• Cohort #2: Post-operative radiation +/- chemotherapy for intermediate and high risk factors

  • Any FIGO stage

  • Status post any definitive surgical procedure (e.g. radical hysterectomy and lymph node dissection) and on final pathology found to have risk factors:

    • Intermediate risk: Lymphovascular space invasion (LVSI), deep cervical stromal invasion, tumor size > 4 cm
    • High risk: pelvic or para-aortic lymph nodes, parametrial invasion, positive surgical margins
  • Plan to undergo pelvic +/- para-aortic radiotherapy with or without chemotherapy per standard of care

• Cohort #3: 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

• Cohort #4: Systemic treatment for recurrent or metastatic disease

  • Any recurrence (local, regional, or distant) after prior treatment for cervical cancer
  • Metastases at first diagnosis without prior treatment

Exclusion Criteria:

• 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 Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cohort 1 (surgery patients); 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).	Procedure: Biospecimen Collection; Undergo collection of blood samples
Cohort 2 (post-operative radiation +/- chemotherapy patients); 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).	Procedure: Biospecimen Collection; Undergo collection of blood samples
Cohort 3 (definitive chemoradiotherapy patients); 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).	Procedure: Biospecimen Collection; Undergo collection of blood samples
Cohort 4 (systemic treatment patients); 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).	Procedure: Biospecimen Collection; Undergo collection of blood samples

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients with undetectable circulating tumor deoxyribonucleic acid (ctDNA) posttreatment in patients with detectable ctDNA pre-treatment	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.	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)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ctDNA levels	Will be associated with Federation of Gynecology and Obstetrics stage and assessed using linear regression, reporting the correlation as well as the model estimates.	Baseline
Clinical tumor response	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.	At post-treatment assessment, assessed up to 2 years
Radiographic tumor response	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.	At post-treatment assessment, assessed up to 2 years
Recurrence-free survival	Baseline ctDNA and ctDNA at measured time points will be considered in Cox models.	Up to 2 years
Overall survival	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.	Up to 2 years
ctDNA clearance kinetics	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.	Up to 2 years
ctDNA conversion	Will be correlated during the active monitoring phase with recurrence-free survival.	Up to 2 years

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Allison E. Garda, M.D., Mayo Clinic in Rochester

Study record dates

Study Major Dates

• Study Start (Actual): November 17, 2020
• Primary Completion (Estimated): November 30, 2024
• Study Completion (Estimated): November 30, 2025

Study Registration Dates

• First Submitted: September 23, 2020
• First Submitted That Met QC Criteria: September 28, 2020
• First Posted (Actual): October 5, 2020

Study Record Updates

• Last Update Posted (Actual): February 28, 2024
• Last Update Submitted That Met QC Criteria: February 26, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Cervical Diseases; Uterine Diseases; Neoplasms, Complex and Mixed; Neoplasms, Squamous Cell; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Uterine Cervical Neoplasms; Carcinoma; Carcinoma, Squamous Cell; Carcinoma, Adenosquamous; Papilloma
• Other Study ID Numbers: ROR1905 (Other Identifier: Mayo Clinic in Rochester); NCI-2020-06965 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); 19-011924 (Other Identifier: Mayo Clinic Institutional Review Board)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No