Whole-body DW-MRI and cfDNA Analysis for the Surveillance of Melanoma Patients at High Risk for Recurrence. (DW-MRi)

Whole-body Diffusion-weighted Magnetic Resonance Imaging and cfDNA Analysis for the Surveillance of Melanoma Patients at High Risk for Recurrence Following Surgery or Systemic Therapy

Patients with locally advanced melanoma are at high risk for recurrence following surgical treatment. More patients with stage IV melanoma remain in complete remission following systemic therapy. No standards have been established for the surveillance of patients at high risk for recurrence. Whole-body diffusion-weighted magnetic resonance imaging and cfDNA analysis of blood are innovative imaging and laboratory investigations that may be of benefit for early detection of recurrence in this patient population.

Study Overview

• Status: Recruiting
• Conditions: Melanoma
• Intervention / Treatment: Other: follow up DW MRI

Detailed Description

Cutaneous melanoma is the most aggressive form of skin cancer. Melanoma is the malignant cancer that originates from the melanocytes of the body (= pigmented cells of the body). Melanoma can originate from the melanocytes that are present in the skin, mucosa, or the uvea of the eye.

The incidence of melanoma is continuing to rise at a rate exceeding all other cancers. Every year approximately 132,000 and 1,000 people will be diagnosed with melanoma and 37,000 and 250 people are expected to die of the disease respectively worldwide and in Belgium. Surgical resection is curative for most cases of early identified and localized melanoma (90% long term survival for stage I disease) . Patients with stage II/III disease are at high risk of relapse after surgery, even when followed by radiotherapy and adjuvant IFN alfa-2b therapy (the risk of recurrence for these patients is 60% to 75%).

In 2010 Romano et al. published a study evaluating the time to relapse and the site of relapse in 340 patients (Figure 1: relapse free survival of all 340 patients with substages IIIA,IIIB and IIIc). Patients and/or family members discovered 62% of local and in-transit recurrences and 49% of nodal recurrences. Only 37% of patients whose first recurrence was systemic detected the recurrence themselves, either by noticing a new tumor or other symptoms that led to further evaluation. Physical examination by a physician accounted for the detection of 36% of the local and in-transit recurrences, Twenty-six percent of nodal recurrences were detected by physicians however only in 9% systemic recurrences did they discover systemic recurrence. In the remaining 63% of patients whose first detectable relapse was systemic, the relapse was asymptomatic. Radiographic tests, largely CT scans (72%), detected asymptomatic systemic relapses in 53% (n_87) of these patients. This study also demonstrated the benefit of identifying early relaps, since symptomatic relapses, as opposed to relapses discovered by physical examination or radiographic imaging, were associated with shorter survival. And confirming that a recurrence that could be completely resected was associated with longer survival (relative risk_2.31; 95% CI, 1.68 to 3.18; P_.001).

In the last several years the therapeutic landscape of melanoma has changed. The introduction of immunotherapy has increased the life expectancy for melanoma stage IV patients and even has the possibility for cure of the disease. This changes the need in screening. Since no therapeutic options were available, there was no need for a strict follow-up. The primary objective of follow-up in these patients with melanoma was to identify potentially curable locoregional recurrences and second primary cancers. Optimal follow-up strategies and intervals have not been determined, and there is no consensus. At a minimum, patients should undergo an annual routine physical examination, including a full skin assessment and palpation of the regional lymph nodes. The role of imaging in the follow-up of high risk patients is not clear. Since the introduction of newer therapies, the need for a more closer follow-up has emerged as well.

The outcome of patients with stage IV disease is grim with less than 50% of patients surviving for more than 12 months. Short-lived tumor responses are obtained in about 10-20% of patients treated with DTIC chemotherapy but no randomized trial could demonstrate a survival benefit for more complex chemotherapy regimens or so-called bio-chemotherapy regimens despite higher response rates.

In march 2011 a CTLA-4 inhibitor, Ipilimumab (Yervoy), was aproved by the FDA. It was the first treatment to prove a survival benefit in melanoma patients. An interesting aspect about the treatment with Ipilimumab is the plateau seen after 2 years.This plateau represents patient with a long term survival benefit of Ipilimumab and even the possibility of 'cure'. The patients in this population now undergo repeated imaging with PET CT and/or CT. This leads to a high radiation burden for this patients. The DW-MRI could in this population have a benefit.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Bart Neyns, MD Phd; Phone Number: 02 477 60 40; Email: bart.neyns@uzbrussel.be
• Study Contact Backup: Name: Yanina JL Jansen, MD; Phone Number: 02 477 91 23; Email: yanina.jansen@uzbrussel.be

Study Locations

• Belgium
  • Brussels, Belgium, 1090
    • Recruiting
    • UZ Brussel
  • Brabant
    • Jette, Brabant, Belgium, 1090
      • Recruiting
      • UZ Brussel

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologically confirmed malignant melanoma;
• AJCC Stage III: No evidence of disease on most recent CT or PET-CT imaging
• Stage IV: Complete remission for more than 3 years, confirmed by most recent CT or PET-CT imaging

Exclusion Criteria:

• Contra-indication for MRI: pacemaker, metallic foreign body in eye, recent operation with prosthetic material (< 6weken)
• Claustrophobia
• Metallic devices implanted such as hip prostheses, since this can alter the imaging quality

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: stage IV melanoma CR>3years; Stage IV: Complete remission for more than 3 years, confirmed by most recent CT or PET-CT imaging	Other: follow up DW MRI; Whole-body diffusion-weighted magnetic resonance imaging and cfDNA analysis; Other Names: cfDNA
Experimental: Stage III Melanoma; AJCC Stage III: No evidence of disease on most recent CT or PET-CT imaging	Other: follow up DW MRI; Whole-body diffusion-weighted magnetic resonance imaging and cfDNA analysis; Other Names: cfDNA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
explorative evaluation of the use of DWMRI in the follow-up of high risk melanoma patients	5years

Secondary Outcome Measures

Outcome Measure	Time Frame
• Distant metastasis-free survival (for stage III patients only), overall survival	5years
• Registration of the nature and result of salvage therapies offered at the time of detection of recurrence/progression	5 years
• Explore the correlation of cfDNA measurements and the clinical or MRI based diagnosis of recurrence/progression	5years

Collaborators and Investigators

• Sponsor: Universitair Ziekenhuis Brussel
• Investigators: Principal Investigator: Bart Neyns, Md Phd, Universitair Ziekenhuis Brussel

Study record dates

Study Major Dates

• Study Start: November 1, 2014
• Primary Completion (Anticipated): November 1, 2025
• Study Completion (Anticipated): November 1, 2025

Study Registration Dates

• First Submitted: September 14, 2016
• First Submitted That Met QC Criteria: September 14, 2016
• First Posted (Estimate): September 20, 2016

Study Record Updates

• Last Update Posted (Actual): December 17, 2020
• Last Update Submitted That Met QC Criteria: December 16, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: cfDNA; surveillance; complete remission; DW-MRI
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Disease Attributes; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Recurrence; Melanoma
• Other Study ID Numbers: 2014-BN-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: anonymous