Dynamic ctDNA Assessment in Cervical and Anal Canal Tumors: Optimizing Follow-up and Clinical Outcomes

Sponsor
Instituto do Cancer do Estado de São Paulo
Study ID
NCT06640283
Phase
PHASE2
Status
Recruiting
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Conditions

  • Anal Canal Cancer
  • HPV-Related Anal Squamous Cell Carcinoma
  • HPV-Related Carcinoma
  • HPV-Related Cervical Carcinoma
  • Uterine Cervical Cancer

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • ctDNA test — DIAGNOSTIC_TEST
    ctDNA involves the collection of peripheral blood samples for the analysis of circulating tumor DNA (ctDNA). The samples are processed using next-generation sequencing (NGS) and/or digital polymerase chain reaction (PCR) techniques to detect specific genetic alterations related to the tumor. The objective is to assess the presence and quantity of ctDNA, providing information on tumor burden and treatment response.
  • Pembrolizumab — DRUG
    Participants will receive the institution's standard treatment during Phase I. If ctDNA remains positive between 8 and 12 weeks after the standard treatment, the participant will be invited to proceed to Phase II, which will consist of intravenous immunotherapy for up to 12 months, or until disease progression or unacceptable toxicity occurs. Continuous monitoring with ctDNA testing will be performed during Phase II.

Study Details

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.

Key Dates

Start date
Mar 14, 2025
Status verified
Dec 2025
Primary completion
Dec 31, 2026
Completion
Jan 31, 2027

Study Design

Enrollment
150 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT

Arms

  • Other: Active laboratory monitoring
    Phase I Monitoring through collection of laboratory tests
  • Experimental: Intervention with Immunotherapy
    Phase II for participants who are ctDNA positive after standard treatment. Intervention will be with Pembrolizumab

Primary Outcome Measure

General Objective [ Time Frame: 2 years ]

Central Contacts

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