Symptoms and General Pathology

All Conditions

Neoplasms

Digestive System Diseases

Recurrence

Colorectal Neoplasms

Adenocarcinoma

Neoplasm, Residual

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Neoplastic Processes

Claus L Andersen, PhD

Christina Demuth, PhD

Nis Hallundbæk Schlesinger

Mads F Klein, MD, Ph.D

Jeppe Kildsig, MD

Lene H Iversen, MD, DMSc

Claudia Jaensch, MD, PhD

Kåre A Gotschalck, MD, Ph.D

Peter Bondeven, MD, PhD

Uffe S Løve, MD, PhD

Ole Thorlacius-Ussing, MD, PhD

Per Vadgaard Andersen, MD, PhD

Kåre A Gotschalck, MD, PhD

Approximately two-thirds of all colorectal cancer patients undergo surgery with the aim of curing them. However, despite the surgery, 20-25% of them experience relapse. It is possible to reduce the risk of relapse with chemotherapy, but as chemotherapy is associated with significant side effects, it is only given to patients at high risk of relapse. Currently, the risk is assessed based on an examination of the removed tumor tissue.

In a previous research project, blood samples were taken after patients' surgery and examined for the presence of circulating tumor DNA (ctDNA). When cancer cells in solid tumors die, they release DNA, which can be detected in the blood. DNA in the blood has a half-life of less than 2 hours, so if ctDNA is found in a blood sample taken, e.g., 14 days after surgery, the patient most likely still has cancer cells in their body.

The results show that if a patient has ctDNA in their blood after surgery, the risk of relapse is high. The presence of ctDNA in the blood has the potential to be a better indicator of the risk of future relapse than the tumor examination used today. Therefore, ctDNA analysis has the potential to become a marker that will be used in the future clinical setting for monitoring colorectal cancer.

The overall objective of this study is to confirm that ctDNA found in a blood sample after intended curative treatment for CRC is a marker of residual disease and risk of recurrence and is applicable in clinical practice.

Colorectal cancer (CRC) is the third most common cancer worldwide. Approximately 75% of patients initially present with potentially curable disease, but despite curatively intended treatment up to 25 % of them experience a relapse of the disease. Upon diagnosis, survival of CRC can be improved by offering adjuvant chemotherapy to patients with a high risk of recurrence, or by early detection of recurrence enabling early intervention which improves patient survival significantly. To achieve this, it is essential to have sensitive and specific tools for correctly identifying patients with a high risk of recurrence and the need for adjuvant therapy, and for early detection of recurrence facilitating early intervention. Non-invasive analysis of circulating tumor DNA (ctDNA) is an emerging tool that has this potential.

Objectives

The overall objective of the study is to confirm that ctDNA detected after intended curative treatment for CRC is a marker of residual disease and risk of recurrence and is applicable in clinical practice.

Primary objectives

P1: To determine the prognostic value of a patient's ctDNA status and compare it with other known prognostic factors. Specifically, the aim is to determine the association between 3-year disease-free survival (DFS) and ctDNA detection status immediately after 1) curative-intended surgery and 2) adjuvant chemotherapy.

P2: To identify a cohort of UICC stage III CRC patients with planned adjuvant chemotherapy. These patients will be offered enrollment in the DANISH.MRD part II (Secondary objective 1 (S1)), and will further be included in a European collaboration named GUIDE.MR-01-CRC, funded by the European Union via the Innovative Health Initiative.

Secondary objectives

S1: To technically assess, compare, and rank commercial ctDNA diagnostics and evaluate their performance after intended-curative CRC treatment (postoperatively and post adjuvant chemotherapy) to identify the best-performing method at each time point.

S2: To assess the effect of standard-of-care adjuvant chemotherapy on the level of ctDNA. Especially, for patients with ctDNA detected after surgery, the aim is to measure and compare the ctDNA levels in plasma samples drawn before and after adjuvant chemotherapy. Further, the change in ctDNA level will be correlated to the oncological outcomes (time to clinical recurrence, disease-free survival, and overall survival).

S3: To investigate if time to Molecular recurrence determined using serial ctDNA analyses in longitudinally collected plasma samples is shorter than time to Clinical recurrence using standard-of-care radiological imaging.

S4: To investigate the correlation between ctDNA analysis results and findings on CT scans. ctDNA analysis will be restricted to blood sampling times that coincide with standard-of-care CT scans (at 12 and 36 months postoperatively). If ctDNA analysis can predict the outcome of the CT scan, the potential is that ctDNA analysis in the future can guide when to perform CT scans.

S5: To investigate the prognostic power of ctDNA at the time point of indeterminate CT scans.

S6: To investigate, if molecular characterization of CRC cancers can stratify patients and predict i.e., treatment response, growth patterns, cancer aggressiveness, clinical outcomes, and whether the tumor sheds ctDNA into the circulation.

Investigational plan

The DANISH.MRD study is logistically divided into two parts, and patients are offered participation in each part separately. The parts are called "DANISH.MRD part I - Surgery", and "DANISH.MRD part II - Surveillance".

In DANISH.MRD part I blood samples are collected before and after surgery. For patients receiving neoadjuvant therapy, a blood sample will also be collected before initiation of this treatment.

In DANISH.MRD part II blood samples are collected immediately after adjuvant chemotherapy and during standard-of-care surveillance.

Patients included in DANISH.MRD part I will help address Primary objective 1 (P1). The subset of the part I patients that are also included in DANISH.MRD part II will help to address the Secondary objectives S1-S6.

Both Part I and Part II DANISH.MRD patients receive standard follow-up care, which includes scheduled visits for up to 5 years following their surgery.

Sample collection for DANISH.MRD part I - Surgery (Objectives P1-2, S1-S5)

* Blood sampling preoperatively and after surgery (between days 20-30, but before initiation of adjuvant chemotherapy)
* Sampling of tissue from the resected specimen

Sample collection in DANISH.MRD part II - Surveillance (objectives S1-S5)

* Blood sampling post-adjuvant chemotherapy (ACT): postACT (14-30 days after the end of ACT), and at months 8, 12, 16, 20, 24, 30 and 36 postoperatively.

Tumor tissue

Normal tissue

Whole blood (processed to plasma, buffycoat and serum)

Dried blood spots.

DANISH.MRD: Danish Assessment of Minimal Residual Disease by Liquid Biopsies

Danish Assessment of Minimal Residual Disease by Liquid Biopsies

Especially, the association between 3-year disease-free survival and ctDNA status after surgery and after adjuvant chemotherapy

Technical assessment to compare and rank commercial ctDNA diagnostics and evaluate their performance after surgery and adjuvant chemotherapy

Assessment of the effect of standard-of-care chemotherapy on the level of ctDNA

Assessment of the time between molecular recurrence (ctDNA positive blood sample) and clinical recurrence (standard-of-care radiological imaging)

ctDNA status on blood samples coinciding with standard-of-care CT scans (at 1 and 3 years after surgery), to see if ctDNA analysis can predict the outcome of the CT scan

Investigation of the use of molecular characterization to stratify patients and predict i.e., treatment response, growth patterns, cancer aggressiveness, clinical outcomes, and whether the tumor sheds ctDNA into the circulation

Aarhus University Hospital

University of Aarhus

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Rare Diseases

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Carcinoma

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Disease Attributes

Ovarian Cancer

Ovarian Epithelial Cancer

\[68Ga\]-FAPI is tumor imaging agent for use with Positron Emission Tomography (PET) imaging for the detection of Fibroblast Activation Protein (FAP) positive cancer cells and cancer-associated fibroblasts (CAF)

68Ga-FAPI

Tingting Wang, PH.D

Jianjun Liu, PH.D

This is a prospective study to investigate the potential efficacy of 68Ga-FAPI PET/CT for recurrence detection of epithelial ovarian cancer in comparison with 18F-FDG PET/CT.

Gallium 68-labeled fibroblast-activation protein inhibitor (68Ga-FAPI) has recently been a potential radiotracer for gynecological malignancies,including ovarian cancer. Early detection and localization of sites of recurrence helps to identify ovarian cancer patients who will benefit the most from secondary surgery, chemotherapy, or radiation therapy. Its clinical utility for recurrence detection of epithelial ovarian cancer and histological validation of FAPI findings is not well established.

Surgical or biopsy tumor tissue specimens

Clinical Application of 68Ga-FAPI PET Imaging in Detection of Ovarian Cancer Recurrence

Sensitivity and Specificity of 68Ga-FAPI PET/CT for recurrence in comparison with 18F-FDG PET/CT

Measurement of the maximum standardized uptake value of the lesion

TBR was calculated according to the formula：TBR=SUVmax of lesion/SUVmax of background

Correlation between 68Ga-FAPI PET uptake intensity and histopathologic FAP expression. Validation via immunohistochemical FAP staining of pathological specimen

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
DANISH.MRD: Danish Assessment of Minimal Residual Disease by Liquid Biopsies	NCT06076811	Colorectal Neop... Colorectal Canc... Colorectal Aden... Colorectal Canc... Colorectal Canc... Colorectal Canc...		18 Years -	University of Aarhus
DANISH.MRD: Danish Assessment of Minimal Residual Disease by Liquid Biopsies	NCT06076811	Colorectal Neop... Colorectal Canc... Colorectal Aden... Colorectal Canc... Colorectal Canc... Colorectal Canc...		18 Years -	University of Aarhus
Clinical Application of 68Ga-FAPI PET Imaging in Detection of Ovarian Cancer Recurrence	NCT05856409	68Ga-FAPI Ovarian Cancer Epithelial Ovar... Positron Emissi...	68Ga-FAPI	18 Years - 80 Years	RenJi Hospital

Spots Global Cancer Trial Database for recurrence detection