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Malignant Melanoma, MetastaticEarly Phase 1MPAKNCT02591654

MRI and PET to Assess Pembrolizumab Response

A Early Phase 1 study testing Pembrolizumab and FLT PET in people with Malignant Melanoma, Metastatic, run by Columbia University at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

The purpose of this study is to test two imaging techniques, one called whole body (WB) diffusion weighted (DWI) magnetic resonance imaging (MRI) (WB-DWI MRI), and another called Fluorine-18 3'-deoxy-3'-fluorothymidine positron emission tomography (PET) (F-18-FLT PET). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Malignant Melanoma, Metastatic
What is being tested?
Pembrolizumab and FLT PET
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
6 participants
Where
1 siteUnited States
Study dates
Oct 2015to Oct 2022
Phase
Early Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically confirmed diagnosis of melanoma
  • Stage III or stage IV metastatic melanoma
  • Disease that is measurable. This is defined as lesions measuring at least 10mm on radiologic imaging. For lymph node disease, the lesion must measure at least 15 mm or have been biopsied and shown to contain melanoma. Skin or mucosal lesions that are not measurable on radiologic imaging but measure at least 10mm on clinical exam are also acceptable. (See Section 13.2 for detailed definition of measurable disease)
  • Disease is termed unresectable or the patient refuses resection
  • The Eastern Cooperative Oncology Group (ECOG) performance status of 1 or better
  • Age ≥18 years. This is due to the limited data with pembrolizumab in children younger than 18 years of age.
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  • Normal organ and marrow function as defined below
  • Aspartate aminotransferase (AST) (SGOT) or alanine aminotransferase (ALT) (SGPT) ≤2.5 × institutional upper limit of normal (≤5 x upper limit of normal for patient with liver metastasis)
  • Total bilirubin within 1.5 x institutional level of normal or direct bilirubin ≤ upper limit of normal (ULN) for patient with total bilirubin levels > 1.5 ULN)
  • Hemoglobin ≥ 9.0g/dL or ≥5.6mmol/L
  • Absolute neutrophil count ≥1,000/microliters (mcL)
  • Platelets ≥ 75,000/mcL
  • The effects of pembrolizumab on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of pembrolizumab administration.
  • Women of child-bearing potential must have a negative urinary or serum pregnancy test.

Who cannot join

  • Prior therapy with anti-PD-1 antibody
  • The patient has symptomatic brain metastases. Asymptomatic brain metastases are permitted provided that there is no steroid requirement, no more than 4 metastases detected on standard MRI imaging, no metastatic brain lesion that is > 3 cm in size, and no lepto-meningeal disease.
  • Patient has not recovered to Grade 0-1 from adverse events due to prior chemotherapy, radiation, or biological cancer therapy (including monoclonal antibody (mAb)).
  • The patient is not recovered from minor or major surgery and is less than 4 weeks from major surgery prior to starting treatment with pembrolizumab
  • Significant auto-immune disease requiring hospitalization within the past two years or any history of life-threatening auto-immune disease
  • Immunosuppressive therapy including systemic corticosteroids except for maintenance dosing for adrenal insufficiency
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  • Concurrent use of any other investigational agents
  • Active central nervous system metastasis and/or carcinomatous meningitis causing symptoms.
  • Known additional malignancy that is progressing or requires active treatment with the exceptions of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.
  • Active autoimmune disease or a syndrome that requires systemic steroids or immunosuppressive agents with the exceptions of replacement dose steroids for adrenal insufficiency, vitiligo, resolved childhood asthma/atopy, intermittent use of inhaled steroids, local steroid injections, hypothyroidism stable on hormone replacement, and Sjogren's syndrome
  • Active tuberculosis
  • Hypersensitivity to pembrolizumab or any of its excipients.
  • Expected to require any other form of systemic antineoplastic therapy while receiving pembrolizumab
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, autoimmune diseases, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Patients with a pacemaker, stainless steel aneurysm clip or any other magnetic resonance (MR) contraindicated implant or foreign body would warrant exclusion from this study. Pacemakers may be reprogrammed or turned off by the strong MRI magnetic field. Radio-frequency (RF) fields in MR can also cause severe heating of pacemaker lead tips. Steel aneurysm clips are prone to torque in the strong MR field which can displace the clips and may damage the vessel, resulting in hemorrhage, and/or death.
  • All patients and volunteers are screened before MR examination using a MRI safety screening Questionnaire as part of the New York Presbyterian/Columbia University Medical Center (NYP/CUMC) MRI safety policy. Any patient who would normally be excluded by this screening process would also be excluded from this study.
  • Pregnant or breastfeeding women are excluded from this study because of the unknown effects of the study agent on the unborn child and the possible adverse impact of immune activation on pregnancy. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with pembrolizumab breastfeeding should be discontinued if the mother is treated with pembrolizumab.
  • Male who is expecting to father a child during the treatment period.
  • History of pneumonitis requiring hospitalization or systemic immune suppressive therapy.
  • Significant immunodeficiency making the patient unlikely to benefit from pembrolizumab therapy including a diagnosis of acquired immune deficiency syndrome (AIDS), active hepatitis B or hepatitis C, or organ transplant requiring immunosuppressive therapy.
  • Received a live virus vaccine within 30 days of planned start of therapy

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Columbia University Irving Medical Center / NewYork-Presbyterian Hospital

    New York, New York, 10032

Other trials in United States

About this study

Official title: A Feasibility Study of MRI and PET Imaging to Assess Response to MK-3475 (Pembrolizumab) in Patients With Metastatic Melanoma

The purpose of this study is to test two imaging techniques, one called whole body (WB) diffusion weighted (DWI) magnetic resonance imaging (MRI) (WB-DWI MRI), and another called Fluorine-18 3'-deoxy-3'-fluorothymidine positron emission tomography (PET) (F-18-FLT PET). The goal is to see whether these imaging techniques would allow the study doctors to see changes in the size of a tumor earlier for patients with metastatic melanoma receiving Pembrolizumab (MK-3475).

Read the detailed description

There is a growing body of evidence that demonstrates that tumor proliferation, measured classically by immunohistochemical evidence of increased Ki-67 expression, can be reliably determined in vivo using radiolabeled thymidine. The development of [18F]-fluorothymidine (FLT) PET has been reliably identified as a marker of cellular proliferation, and has been shown to identify changes in proliferation in successfully treated patients.

Being tested
Pembrolizumab, FLT PET
Keywords
FLT, Pembrolizumab, Metastatic Melanoma, MK-3475
Medical subject headings
Melanoma, Neoplasm Metastasis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PembrolizumabDrug

    Also called MK-3475

    Each patient will receive pembrolizumab 200mg administered as a 30 minute intravenous (IV) infusion every 3 weeks for an indefinite period.

  • FLT PETDrug

    Also called [18F]-fluorothymidine (FLT) PET

    FLT PET/CT is increasingly being utilized as an early PD biomarker in cancer given the close association between FLT uptake and proliferative index.

Study groups in NCT02591654
Study groupRoleWhat they receive
Pembrolizumab and FLTExperimentalSubjects will receive WB-DW MRI and FLT PET to assess disease burden after receiving pembrolizumab.
Receives: Drug: Pembrolizumab; Drug: FLT PET

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Prevalence of lesion detection (sensitivity)

    Sensitivity of WB-DW MRI and FLT-PET imaging in lesion detection and evaluation for metastatic melanoma.

    Measured: Baseline

Secondary outcomes (4)

  1. Difference in lesion metrics

    Lesion metrics including diameter and intensity as measured by FLT-PET and WB-DWI MRI will be compared with standard RECIST and volumetric criteria as well as Immune Response Criteria (IRC).

    Measured: Baseline, 2 years

  2. Change in patient response (immunoscore)

    Assessed by programmed cell death protein 1 (PD-1), programmed death-ligand 1 (PD-L1), and programmed death-ligand 2 (PD-L2) expression, quantification of infiltrating cluster of differentiation 8 (CD8+) T cells at the invasive margin and within the center of the tumor, and assessment of cluster of differentiation 2 (CD2) expression. Formalin fixed paraffin embedded sections will be used. Cluster of differentiation 3 (CD3) and CD8 will be stained for and the immunoscore will be calculated using standard methods.

    Measured: Baseline, 2 years

  3. Change in patient response (expression levels)

    Assessed by NanoString with measurement of immune related genes. Expression levels will be compared pre-treatment and post-treatment.

    Measured: Baseline, 2 years

  4. Change in RECIST Index

    Index lesions identified on the baseline standard Response Evaluation Criteria In Solid Tumors (RECIST) image set will be evaluated for changes in FLT maximum standardized uptake value (SUVmax) and standardized uptake volume (SUVvol), and changes in antibody-drug conjugate (ADC) on DWI MRI at 6 weeks compared with baseline. These early response measures will then be compared with RECIST response measurements on conventional imaging.

    Measured: Baseline, 6 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Oct 2015 (estimated)
  2. Study startOct 2015
  3. Primary completionOct 2022
  4. Study completionOct 2022

Why it stopped: Poor enrollment

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Early Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
6 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02591654
Sponsor's protocol ID
AAAO2558
Acronym
MPAK
Status last verified
Dec 2022
First submitted
21 Oct 2015
Last updated
30 Dec 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing Pembrolizumab and FLT PET in people with Malignant Melanoma, Metastatic, run by Columbia University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 30 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Poor enrollment). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Prevalence of lesion detection (sensitivity) (time frame: Baseline). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02591654.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Dec 2022.

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