Clinical trial NCT06640283: Dynamic ctDNA Assessment in Cervical and Anal Canal Tumors: Optimizing Follow-up and Clinical Outcomes
Official title: Dynamic Assessment of ctDNA in Patients With Cervical and Anal Canal Tumors to Optimize Follow-up and Clinical Outcomes in the Brazilian Unified Health System (SUS)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: HPV-Related Carcinoma
Uterine Cervical Cancer
Anal Canal Cancer
HPV-Related Anal Squamous Cell Carcinoma
HPV-Related Cervical Carcinoma
Keywords: HPV
ctDNA
Cervical tumors
Anal canal tumors
Molecular diagnosis
Diagnostic test
Biomarkers
Lead sponsor: Instituto do Cancer do Estado de São Paulo
Sponsor class: OTHER
Collaborators: name: Conselho Nacional de Desenvolvimento Científico e Tecnológico
First posted: 2024-10-15
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: 84 to150 patients will be tested for HPV in their tumor samples 68 patients with negative ctDNA after CRT will be monitored with ctDNA plus routine image 16 patients with positive ctDNA after CRT will receive anti-PD1
Primary purpose: TREATMENT

Brief summary: After definitive radiotherapy (RT) treatment (with or without chemotherapy), cervical and anal canal neoplasms frequently exhibit disease persistence or recurrence. Due to the local inflammatory process post-treatment, response assessment by imaging (current gold standard) is limited, often necessitating multiple follow-ups and repeated invasive biopsies. Conventional follow-up is complex and costly, requiring equipment from secondary and tertiary services, trained radiologists, and patient exposure to radiation and contrast.

In this context of human papillomavirus(HPV)-related neoplasms, recent studies have demonstrated the role of ctDNA (circulating tumor DNA) in assessing the risk of recurrence or disease progression, providing a rationale for using the tool in two fronts:

* Optimizing follow-up based on serial monitoring of ctDNA;
* Selecting patients with positive ctDNA after RT, who are at high risk of recurrence, for treatment intensification.

Monitoring with ctDNA as a standalone follow-up tool in cases evolving with negative ctDNA after RT has the potential to replace imaging exams, being a minimally invasive test performed on a peripheral blood sample. Currently, ctDNA testing has expensive methodologies not available in the Unified Health System (SUS). This project aims to develop a methodology for ctDNA evaluation focused on HPV ctDNA research that is low-cost and executable in SUS, as well to assess the accuracy of this test in the population with HPV-related tumors.

Additionally, we will evaluate whether the early introduction of immunotherapy in patients with positive ctDNA after definitive treatment can increase cure rates. Immunotherapy already has a well-defined role in the treatment of metastatic HPV-related neoplasms. Recently, the use of anti-programmed death-1 (anti-PD1) has also shown benefits in patients with locally advanced cervical cancer with a high risk of recurrence who are candidates for chemoradiotherapy (CRT). Therefore, its use focused on HPV-related tumors, as well as a better understanding of which patients benefit from this strategy, warrants further investigation.

Detailed description: The ANA study is a research project aimed at enhancing the treatment and outcomes for patients with cervical and anal canal cancer by using innovative diagnostic and therapeutic methods. The study consists of the following phases:

* Patient identification and selection;
* Recruitment of patients diagnosed with cervical or anal canal cancer who are candidates for treatment with radiotherapy (RT), with or without chemotherapy: patients will be selected based on specific criteria to ensure a representative cohort;
* Development and validation of the ctDNA HPV Test: development of a sensitive and specific test to detect HPV DNA in the blood. This test will undergo rigorous validation to ensure its accuracy and reliability;
* ctDNA monitoring: blood samples collection from patients during treatment and follow-up. ctDNA levels will be monitored in real-time to early detection of residual or recurrent disease. This non-invasive method aims to provide a more accurate assessment of treatment efficacy and disease progression. The results of ctDNA will be compared with traditional imaging methods.
* Complementary immunotherapy treatment: patients with positive ctDNA results after (chemo)radiotherapy will be considered for additional immunotherapy. This phase will evaluate the benefits of combining immunotherapy with standard (chemo)radiotherapy in order to improve patient outcomes;
* Follow-up and outcome evaluation: long-term follow-up of patients to assess clinical outcomes, including survival and quality of life.

The ANA study aims to set new standards in the follow-up and management of HPV-related cervical and anal canal cancer by improving patient care within the Brazilian public health system (SUS).

Eligibility criteria: Inclusion Criteria:

1. Histological diagnosis of anal canal or cervical cancer.
2. Documented presence of HPV.
3. Locally confined or locally advanced disease, defined as:

   1. Anal canal carcinoma stage I to III, according to American Joint Committee on Cancer (AJCC) 8th edition;
   2. Cervical carcinoma stage I B2 to IV A, according to AJCC 8th edition.
4. Indication for definitive treatment with radiotherapy, with or without concomitant chemotherapy.
5. Eastern Cooperative Oncology Group (ECOG)-Performance Status (PS) 0 - 1.
6. Age ≥ 18 years.
7. Signing of the Informed Consent Form (ICF).
8. HIV-positive patients may be included if Cluster of Differentiation 4(CD4) count is greater than or equal to 200.
9. Patients may participate in other concurrent studies, as long as they do not involve interventions related to the treatment of the underlying cancer.

Exclusion Criteria:

1. Patients with unequivocal distant metastasis at diagnosis.
2. For participants with positive ctDNA after treatment, those candidates for participation in Phase II will be excluded if there is unequivocal radiological progression in the first imaging exam after the completion of radiotherapy (with or without chemotherapy) or routine indication for salvage surgery immediately after the conclusion of definitive treatment.
3. Need for recurrent blood transfusions, such as weekly frequency.
4. Another uncontrolled disease representing a life risk, as determined by medical judgment.
5. Personal history of another active invasive malignant neoplasm in the last 5 years, except for non-melanoma skin carcinomas and in situ carcinomas.
6. Pregnant individuals.
7. Active opportunistic infection or disease.
8. History of autoimmune diseases.

Primary outcomes:
measure: General Objective
timeFrame: 2 years
Secondary outcomes:
Other outcomes:
measure: Number of HPV-focused ctDNA tests developed and validated
timeFrame: 2 years
measure: Performance of the validated HPV-related ctDNA test
timeFrame: 2 years
measure: Comparison of accuracy between standard ctDNA and HPV-focused ctDNA
timeFrame: 2 years
measure: Comparison with Commercially Available HPV ctDNA Tests
timeFrame: 2 years
measure: Comparison of performance between the locally developed HPV ctDNA test and commercially available tests
timeFrame: 2 years
measure: Direct costs of the ctDNA test
timeFrame: 2 years
measure: Disease progression reduction rate with the use of immunotherapy
timeFrame: 2 years
measure: Influence of PD-L1 expression and HPV type on immunotherapy response
timeFrame: 2 years
measure: Correlation between PD-L1 expression and HPV type with immunotherapy response
timeFrame: 2 years
Locations:
city: São Paulo
country: Brazil
facility: Instituto do Câncer do Estado de São Paulo - ICESP
Study officials:
affiliation: Oncologist
name: Maria DP Estevez Diz, Doctor
role: PRINCIPAL_INVESTIGATOR
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