IL2 Imaging in Metastatic Melanoma

March 19, 2020 updated by: G.A.P. Hospers, University Medical Center Groningen

[18F]FB-IL2 Imaging of T Cell Response as Biomarker to Guide Treatment Decisions in Metastatic Melanoma Patients

T cell infiltration of tumor lesions is a known prognostic factor in several tumor types and is used as treatment mechanism in some of these tumor types. In metastatic melanoma, treatment with immune checkpoint inhibitors induces clinical benefit in about 30-50% of the patients. These immune-based therapies are however accompanied by serious immune-related adverse events and high costs.

Tumor infiltrating T cells express the high affinity interleukin-2 (IL2) receptor on their surface. These T cells could therefore be visualized by molecular imaging with a radio-labelled ligand for this receptor. For this purpose, the investigators have developed the PET tracer [18F]FB-IL2.

The study commences with a biodistribution study (phase 1) in 5 subjects. Thereafter the main study (phase 2) starts, in which 25 subjects will receive two [18F]FB-IL2 PET scans at baseline and week 6 of treatment with either ipilimumab, nivolumab, pembrolizumab or the combination of ipilimumab and nivolumab. If [18F]FB-IL2 PET is able to detect a response to treatment, it could serve as a non-invasive early indicator of T cell response to the treatment. Besides, accumulation of the PET tracer in non-target tissue could indicate infiltration of activated T cells in normal organs and thus may predict the development of an immune-related adverse event.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

19

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
      • Groningen, Netherlands, 9713 GZ
        • University Medical Center Groningen

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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:

  1. Has signed informed consent.
  2. ≥18 years of age.
  3. Histologically confirmed cutaneous metastatic melanoma (Stage IV).
  4. Evidence of at least one measurable metastatic lesion based on RECIST version 1.1.
  5. At least one easy accessible metastatic melanoma lesion, of which biopsy can be performed.
  6. Eligible for treatment with ipilimumab, nivolumab, pembrolizumab, or the combination of ipilimumab and nivolumab.
  7. No contraindication for performing a CT scan.
  8. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1.
  9. Women with child-bearing potential and men with reproductive potential must be willing to practice acceptable methods of birth control during the study.
  10. Must have adequate organ function (e.g. liver, kidney) as defined

Exclusion Criteria:

  1. Pre-existing auto-immune disease, which could be exacerbated by ipilimumab (e.g. Crohn, Hashimoto's Thyroiditis).
  2. Presence of malignancy other than the disease under study within 5 years of study enrolment. Subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible.
  3. Brain metastases that are symptomatic or not stable for 8 weeks (must be documented by imaging).
  4. The use of corticosteroids (at the start of treatment). Note: Corticosteroids are allowed during the study for immune-related toxicity of immunotherapy, as this will not interfere with activity of immunotherapy.
  5. Evidence of active infection requiring antibiotic therapy at start of treatment.
  6. Current use of a prohibited medication or requirement of any of these medications during treatment with immune-checkpoint inhibitors as mentioned in the summary of product characteristics (SPC) for Yervoy, Opdivo, and Keytruda.
  7. Known immediate or delayed hypersensitivity reaction to ipilimumab, nivolumab or pembrolizumab or excipients.
  8. Unresolved toxicity of National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. Grade 2 or higher from previous anti-cancer therapy, except alopecia.

  9. A history or evidence of cardiovascular risk including any of the following:

    1. A history or evidence of current clinically significant uncontrolled arrhythmias;
    2. A history of acute coronary syndromes (including myocardial infarction or unstable angina), coronary angioplasty, or stenting within 6 months prior to randomization.
    3. A history or evidence of current ≥Class II congestive heart failure as defined by the New York Heart Association (NYHA) guidelines.
    4. Abnormal cardiac valve morphology (≥grade 2) documented by echocardiogram (subjects with grade 1 abnormalities [i.e., mild regurgitation/stenosis] can be entered on study). Subjects with moderate valvular thickening should not be entered on study.
    5. Presence of cardiac metastases.
  10. Any serious or unstable pre-existing medical conditions (i.e. diabetes mellitus, hypertension, etc), psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol; or unwillingness or inability to follow the procedures required in the protocol.
  11. Altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent.
  12. Pregnant or nursing females.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: IL2-PET scan
[18F]FB-IL2 PET scan, Tumor biopsy, CT scan, Biopsy of non-target tissue
Device: IL2-PET scan
All patients in this study will undergo a IL2 PET scan at baseline and week 6 of treatment with immunotherapy.
Other Names:
  • [18F]FB-IL2 PET scan
Procedure: Tumor biopsy
A procedure to acquire tissue of a predetermined melanoma metastasis will be performed in all patients that participate in phase 2 of this study.
Device: CT scan
A CT scan of diagnostic quality will accompany all the PET scans and will additionally been made 12 and 16 weeks after start of immunotherapy to evaluate response to treatment.
Procedure: Biopsy of non-target tissue
A biopsy of skin and colon non-target tissue involved in an immune-related side effect is optional in patients that participate in phase 2 of this study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Biodistribution and kinetics of [18F]FB-IL2.
Time Frame: 2 hours
Biodistribution and kinetics will be assessed in the first five patients that participate in this trial (phase 1). A 60-minute dynamic PET scan of the chest and 2 total-body PET scans at 60 and 120 minutes will be acquired to determine tracer kinetics and residence time of the tracer in major organs.
2 hours
The ability of the [18F]FB-IL2 PET to detect a treatment-induced immune response in tumors.
Time Frame: 6 weeks
For detection of a treatment-induced immune response the absolute tracer uptake in tumor lesions will be compared between the scan at baseline and the scan after 6 weeks of treatment with ipilimumab, nivolumab, pembrolizumab or the combination of ipilimumab and nivolumab.
6 weeks
Correlation between tumor uptake of [18F]FB-IL2 with the number of IL2 receptor positive immune cells.
Time Frame: 2 days
The amount of IL2 receptor positive cells will be scored by immunohistochemical staining of tumor biopsy material and will be correlated to the tumor uptake of [18F]FB-IL2.
2 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Correlation between tumor uptake of [18F]FB-IL2 with response to therapy.
Time Frame: 16 weeks
The increase in tumor uptake of [18F]FB-IL2 ofu the tumor lesions on the PET scan at baseline and week 6 of treatment with immunotherapy, will be correlated to radiological response as measured on the CT scans at week 6, 12 and 16 according to the RECIST 1.1 criteria.
16 weeks
To analyze heterogeneity in immune response to treatment between separate lesions, as determined by [18F]FB-IL2 PET.
Time Frame: 16 weeks
Both the heterogeneity between separate lesions in one patient and between lesions in different patients will be determined and if possible will be correlated to treatment response (lesion based).
16 weeks
Treatment induced immune cell activation in non-target tissues and if possible the correlation of PET observations with side effects related to the tissue involved.
Time Frame: 16 weeks
Treatment induced immune cell activation in non-target tissue will be determined by visually comparing the PET results at baseline and after 6 weeks of treatment. In regions with a higher tracer uptake on the week 6 scan the absolute uptake will be determined and this will be correlated to the development of an immune-related adverse event. In case of immune-related side effects localized to the skin or colon, biopsy samples are optional and tissue infiltration of IL2 receptor positive cells can be correlated to [18F]FB-IL2 uptake on PET.
16 weeks
Adverse events of [18F]FB-IL2 PET.
Time Frame: 16 weeks
Adverse events will be recorded. Vital signs and blood parameters will be determined before and after tracer injection and directly after the PET scan for safety reasons.
16 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Medical Center Groningen

Investigators

  • Principal Investigator: G. A. Hospers, MD, PhD, UMCG

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 20, 2016

Primary Completion (Actual)

February 14, 2020

Study Completion (Actual)

February 14, 2020

Study Registration Dates

First Submitted

December 14, 2015

First Submitted That Met QC Criteria

October 3, 2016

First Posted (Estimate)

October 4, 2016

Study Record Updates

Last Update Posted (Actual)

March 23, 2020

Last Update Submitted That Met QC Criteria

March 19, 2020

Last Verified

March 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 22102014

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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