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

Recruiting

• Conditions: Recurrent Cervical Carcinoma; Stage I Cervical Cancer FIGO 2018; Stage IB1 Cervical Cancer AJCC v8; Stage IIA1 Cervical Cancer FIGO 2018; Stage IIA2 Cervical Cancer FIGO 2018; Stage IIIA Cervical Cancer FIGO 2018; Metastatic Cervical Carcinoma; Stage IA Cervical Cancer FIGO 2018; Stage IA1 Cervical Cancer FIGO 2018; Stage 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).

Study Timeline

• Study First Submitted: 2020-09-23
• Study First Submitted QC: 2020-09-28
• Study First Posted: 2020-10-05
• Study Start: 2020-11-17
• Status Verified: 2024-02
• Last Update Submitted: 2024-02-26
• Last Update Posted: 2024-02-28
• Primary Completion: 2024-11-30
• Study Completion: 2025-11-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 60

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

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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

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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 (1)

Mayo Clinic in Rochester; 🇺🇸 Rochester, Minnesota, United States