NOAC9 - Circulating Tumor DNA Guided Follow-Up in Anal Cancer

Study Overview
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Brief Summary
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This study investigates if circulating tumor DNA can improve the detection of early treatment failure or recurrence in localized squamous cell carcinoma of the anus (SCCA) after curative chemoradiotherapy thereby increasing the potential for cure. This will be done by comparing the standard follow-up program with ctDNA guided imaging follow-up. Secondly, the aim is to establish early interventions against late morbidities.

Detailed Description
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Squamous cell carcinoma of the anus (SCCA) is a rare disease with less than 200 new cases in Denmark and Sweden each year and approximately 100 new cases in Norway and Finland but with increasing incidence. Primary treatment is chemo-radiotherapy (CRT) comprising high dose IMRT based radiation therapy with combination chemotherapy of 5-FU and Cisplatin. Overall treatment response is good in small tumors, but less pronounced for high-risk tumors. In absence of complete pathological response after CRT or local recurrence, patients are evaluated for. salvage surgery. The importance of R0 resection on overall survival has been described in several studies. It is suggested that early detection of treatment failure and recurrences increases the chance of possible curative surgery (R0-resection) and thereby overall survival. A follow-up program has 3 purposes To detect lack of complete response to primary treatment Early detection of local or distant recurrences Describing and managing late morbidity Purpose: The main purpose of this follow-up study is to investigate if circulating tumor tDNA can improve detection of early treatment failure or recurrences thereby assisting in increasing the potential for cure. Secondly, to provide evidence for use of imaging and third objective is to establish early intervention against late morbidities.

Official Title
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NOAC9 - A Phase II Randomised Nordic Anal Cancer Group Study on Circulating Tumor DNA Guided Follow-Up

Conditions
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Anal Cancer

Intervention / Treatment
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* Diagnostic Test: AMR B: HPV positive ctDNA guided imaging in follow-up


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with SCCA eligible for definitive (chemo)radiotherapy ≥ 18 of years Written and oral consent Exclusion Criteria: Conditions that will contraindicate blood samples Conditions that will contraindicate a PET-CT scan. Potential lack of compliance to standard FU program and study participation.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: ARM A: HPV positive standard of care follow-up<br>The national follow-up program + collection of blood samples for retrospective translational research | |
| Experimental: ARM B: HPV positive ctDNA guided imaging in follow-up<br>The national follow-up program + ctDNA guided additional imaging + collection of blood samples for retrospective translational research | Diagnostic Test: AMR B: HPV positive ctDNA guided imaging in follow-up<br>* Blood samples in follow-up positive for ctDNA leads to an extra PET-CT scan to detect early treatment failure<br>|
| No Intervention: ARM O: HPV negative observational arm<br>Patients with HPV negative disease will be included in an observational arm (ARM O) ARM O: The national follow-up program + collection of blood samples for retrospective translational research | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease free survival | Disease free survival 2 years from end of therapy | after 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time between ctDNA detected and CT verified recurrences | Lead time between ctDNA detected and CT verified recurrences | after 5 years | 
| Rate of succesful salvage surgery | Rate of succesful salvage surgery | after 5 years | 
| Pattern of failure | Pattern of failure defined as ln-field failures (within GTV-T, GTV-N, CTV or irradiated areas) or out-of-field failures | after 5 years | 
| Disease free survival at 5 years follow-up | Disease free survival at 5 years follow-up | after 5 years | 
| The rate of distant failures | The rate of distant failures | after 5 years | 
| Overall survival | Overall survival from beginning of treatment to death of any cause | 5 years | 
| Explorative analysis of total circulating free DNA (cfDNA) | Explorative analysis of total circulating free DNA (cfDNA) | 5 years | 
| ctDNA assays for HPV negative cases | Analysis of ctDNA in HPV negative cases | 5 years | 
| Acute toxicity | Acute toxicity (CTCAE 5.0) | after 2 and 5 years | 
| Late toxicity | Late toxicity (CTCAE 5.0) | after 2 and 5 years | 
| Health related quality of life | Health related quality of life (EORTC QLQ-ANL27) | after 2 and 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Anal cancer, Circulating Tumor DNA, Plasma HPV, Follow-up