MRI and PET to Assess Pembrolizumab Response

NCT02591654 | Terminated Early Phase 1 DMC FDA Drug

• 1 other identifier: AAAO2558
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief 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). 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).

Conditions

Malignant Melanoma, Metastatic

Keywords

FLT; Pembrolizumab; Metastatic Melanoma; MK-3475

Outcome Measures

Primary Outcomes (1)

• Prevalence of lesion detection (sensitivity)

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

  Baseline

Secondary Outcomes (4)

• Difference in lesion metrics

  Baseline, 2 years

• Change in patient response (immunoscore)

  Baseline, 2 years

• Change in patient response (expression levels)

  Baseline, 2 years

• Change in RECIST Index

  Baseline, 6 weeks

Study Arms (1)

Pembrolizumab and FLT

EXPERIMENTAL

Subjects will receive WB-DW MRI and FLT PET to assess disease burden after receiving pembrolizumab.

Drug: Pembrolizumab; Drug: FLT PET

Interventions

Pembrolizumab DRUG

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

Also known as: MK-3475

Pembrolizumab and FLT

FLT PET DRUG

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

Also known as: [18F]-fluorothymidine (FLT) PET

Pembrolizumab and FLT

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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
• 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
• 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.

Sponsors & Collaborators

• Columbia University: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Columbia University Irving Medical Center / NewYork-Presbyterian Hospital

New York, New York, 10032, United States

Location

Related Links

• Herbert Irving Comprehensive Cancer Center

MeSH Terms

Conditions

Melanoma; Neoplasm Metastasis

Interventions

pembrolizumab; 2-phenyl-6-(2'-(4'-(ethoxycarbonyl)thiazolyl))thiazolo(3,2-b)(1,2,4)triazole

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Yvonne Saenger, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 21, 2015
• First Posted: October 29, 2015
• Study Start: October 1, 2015
• Primary Completion: October 1, 2022
• Study Completion: October 1, 2022
• Last Updated: December 30, 2022

Record last verified: 2022-12

Locations

US (1)