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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Anal Cancer
• Intervention / Treatment: Diagnostic test: AMR B: HPV positive ctDNA guided imaging in follow-up

Detailed Description

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

1. To detect lack of complete response to primary treatment
2. Early detection of local or distant recurrences
3. 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.

• Study Type: Interventional
• Enrollment (Anticipated): 400
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Karen-Lise G Spindler, Professor; Phone Number: 91137244; Email: k.g.spindler@rm.dk
• Study Contact Backup: Name: Louise V Laursen, Secretary; Phone Number: 78454979; Email: louise@oncology.au.dk

Study Locations

• Denmark
  • Aarhus, Denmark, 8000
    • Aarhus University Hospital
    • Contact: Karen-Lise G Spindler
  • Capital Region Of Denmark
    • Herlev, Capital Region Of Denmark, Denmark, 2730
      • Department of Oncology Herlev and Gentofte Hospital
      • Contact: Eva Serup-Hansen
  • The Regions Of Southern Denmark
    • Vejle, The Regions Of Southern Denmark, Denmark, 7100
      • Department of Oncology, Vejle Hospital
      • Contact: Birgitte M. Havelund
• Finland
  • Tampere, Finland, 33520
    • Tampere University Hospital
    • Contact: Pia Österlund
  • Turku, Finland, 20521
    • Turku University Hospital
    • Contact: Annika Ålgars
• Norway
  • Bergen, Norway, 5021
    • Haukeland University Hospital
    • Contact: Janne B Kjersem
  • Oslo, Norway, 0450
    • Oslo University Hospital
    • Contact: Marianne G Guren
  • Tromsø, Norway, 9019
    • University Hospital of North Norway
    • Contact: Magnar Johansen
  • Trondheim, Norway, 7030
    • St. Olav's University Hospital
    • Contact: Eva Hofsli
• Sweden
  • Göteborg, Sweden, 413 45
    • Sahlgrenska University Hospital
    • Contact: Mia Johansson
  • Lund, Sweden, 222 42
    • Skane University Hospital Lund
    • Contact: Anders Johnsson
  • Stockholm, Sweden, 171 64
    • Karonlinska University Hospital
    • Contact: Carl Henrik Shah
    • Contact: Calin Radu
  • Umeå, Sweden, 907 37
    • Norrlands University Hospital
    • Contact: Birgitta Lindh

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: ARM A: HPV positive standard of care follow-up; The national follow-up program + collection of blood samples for retrospective translational research
Experimental: ARM B: HPV positive ctDNA guided imaging in follow-up; 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; Blood samples in follow-up positive for ctDNA leads to an extra PET-CT scan to detect early treatment failure
No Intervention: ARM O: HPV negative observational arm; 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?

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

Collaborators and Investigators

• Sponsor: Aarhus University Hospital
• Collaborators: Danish Comprehensive Cancer Center; Nordic Cancer Union; The regions medicine- and treatment funds
• Investigators: Principal Investigator: Karen-Lise G Spindler, Professor, Department of Experimental Clinical Oncology Aarhus Univeristy Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): October 1, 2022
• Primary Completion (Anticipated): June 1, 2026
• Study Completion (Anticipated): June 1, 2031

Study Registration Dates

• First Submitted: August 22, 2022
• First Submitted That Met QC Criteria: October 5, 2022
• First Posted (Actual): October 10, 2022

Study Record Updates

• Last Update Posted (Actual): October 10, 2022
• Last Update Submitted That Met QC Criteria: October 5, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: Follow-up; Circulating Tumor DNA; Anal cancer; Plasma HPV
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Rectal Neoplasms; Anus Diseases; Anus Neoplasms
• Other Study ID Numbers: 82386

Drug and device information, study documents

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