Minimal Residual Disease in Solid Malignancies

Official title

Interception of Minimal Residual Disease in Solid Malignancies

Overview

The IMRD study is a single-centre, prospective observational study which will investigate the rate of ctDNA (circulating tumor DNA) detection from the start of adjuvant therapy following curative-intent surgery. The study will include patients of age 18 years old or older, who provided informed consent. Eligible patients are affected by one of the following non-metastatic resected tumors: i) breast cancer (BC), ii) non-oncogene addicted (EGFR/ALK-wild type) non-small-cell lung cancer (NSCLC), iii) high-risk and very high-risk prostate cancer, iv) high-grade serous ovarian cancer (HGSOC), and v) gastric cancer. Eligible patients will undergo surgery and receive adjuvant treatment(s) as per standard guidelines. Patients who underwent neoadjuvant treatments and had a complete pathological response (i.e., no residual tumor at surgery following neoadjuvant treatments) will not be eligible for the present study. During adjuvant treatment and following its conclusion, patients will be subjected to instrumental monitoring, as per standard guidelines and clinical practice. For eligible patients, a baseline plasma sample will be collected at the time of surgery (feasibility window) and prior to the start of adjuvant treatments (not prior to 28 from the date of surgery) for assessing the detection of ctDNA. Afterwards, plasma samples will be collected at 3, 6 and 9 months from the start of postoperative adjuvant treatments. For patient specific monitoring, a tumor-informed targeted sequencing panel, using tumor-specific mutations detected with WES, will be employed to gather the most sensitive diagnostic platforms, mitigating the risk of negative cases. At 6 months or upon positive ctDNA detection, either a thoracic-abdominal-pelvic or total-body CT scan will be performed to exclude the presence of overt metastatic disease. All patients included in the study will be monitored with longitudinal ctDNA assessment until one-year or follow-up or until the radiological detection of metastatic disease, whichever will occur first. Additional follow-up will be carried outside the IMRD study and will follow standard clinical protocols and schedules. Being an observational study, no treatment intervention will be applied as per protocol based on the detection or absence of ctDNA. For conducting exploratory analyses, the primary tumors will be retrieved and subjected to WES, and the study will aim to detect molecular tumor variables associated with a lack of ctDNA clearance following curative-intent treatment interventions. The study will be conducted in 2 phases. The first phase aims at verifying the feasibility and sustainability of such approach, based on the identification of at least 15% positive patients. This phase is predicted to be completed within 2 years, and is the object of the present application. If the first endpoint is achieved, we will expand the study to include the co-primary endpoint, which aims at estimating the fraction of patients with persistent ctDNA 6 months post-surgery despite adjuvant therapy.

Interventions

• Biological ctDNA detection
  a baseline plasma sample will be collected at the time of surgery and prior to the start of adjuvant treatments forassessing the detection of ctDNA.

Primary outcome measures

• ctDNA detection after surgery [Time frame: 28 days]
• ctDNA detection at 6 months after the start of adjuvant therapy [Time frame: 6 month]

Secondary outcome measures (6)

• ctDNA detection at 6 months vs baseline [Time frame: 6 months]
• ctDNA detection end of adjuvant therapy [Time frame: up to 8 years]
• ctDNA detection at 6 months and 12-month, 24-month, and 36-month [Time frame: 36-month recurrence-free survival]
• ctDNA detection and radiological diagnosis of metastatic disease [Time frame: up to 8 years]
• Lack of ctDNA clearance [Time frame: up to 8 years]
• Likelihood of ctDNA clearance and recurrence risk [Time frame: up to 8 years]

Eligibility criteria

Inclusion criteria

• Provision of informed consent
• Age ≥18 years
• Eligibility for potentially-curative surgery, regardless of previous neoadjuvant/pre-operative systemic treatment
• Completed adequate pre-surgical staging procedures as per standard clinical practice
• Diagnosis of one of the following:
• Clinical Stage II or III breast cancer
• Clinical Stage II or III NSCLC
• HGSOC, either relapsed after primary treatment, confirmed by biopsy, or suspected on the basis of radiological criteria
• Prostate cancer, with at least one of the following: Gleason Score ≥8, radiologically ≥cT2c, or PSA >10
• Gastric cancer with at least one of the following: Radiological/ecoendoscopic/laparoscopic evidence of node-positive disease, infiltration of the serosa or the surrounding organs, diffuse subtype as histology.

Exclusion criteria

• Unable to provide informed consent
• Unable to undergo surgery
• Radiological evidence of metastatic disease
• Unwilling to be subjected to longitudinal plasma samples collection
• Prior diagnosis of a malignant tumor for which the patients underwent any type of anti-neoplastic treatment within 2 years prior to the study screening

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Other

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07268469 · UID 5046 · L2-397

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗