Glembatumumab Vedotin in Treating Patients With Metastatic or Locally Recurrent Uveal Melanoma

Phase 2

Completed

Conditions: Recurrent Uveal Melanoma
Stage IV Uveal Melanoma AJCC v7

Interventions: Drug: Glembatumumab Vedotin
Other: Laboratory Biomarker Analysis
Other: Pharmacological Study

Registration Number: NCT02363283

Lead Sponsor: National Cancer Institute (NCI)

Brief Summary: This phase II trial studies how well glembatumumab vedotin works in treating patients with middle layer of the wall of the eye (uveal) melanoma that has spread to other parts of the body (metastatic) or has returned at or near the same place after a period of time during which the cancer could not be detected (locally recurrent). Glembatumumab vedotin may shrink the tumor by binding to tumor cells and delivering tumor-killing substances to them.

Detailed Description: PRIMARY OBJECTIVES:

I. To characterize the clinical anti-tumor activity of CDX-011 (glembatumumab vedotin) as a single-agent in the treatment of patients with metastatic uveal melanoma.

SECONDARY OBJECTIVES:

I. Description of the clinical safety and benefit of CDX-011 (glembatumumab vedotin) and pharmacodynamics changes in glycoprotein NMB (glycoprotein \[transmembrane\] NMB) (GPNMB) expression.

TERTIARY OBJECTIVES:

I. Characterization of the anti-tumor immunophenotype of patients receiving treatment.

II. Post hoc, correlation of rash with clinical benefit, or lack of rash with lack of benefit, will also be explored.

OUTLINE:

Patients receive glembatumumab vedotin intravenously (IV) over 90 minutes every 3 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 30 days.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 37

Inclusion Criteria

Patients must have histologically or cytologically confirmed metastatic or locally recurrent uveal melanoma; because histologic or cytologic confirmation of primary uveal melanoma is not always possible, confirmation of the clinical diagnosis of uveal melanoma by the treating investigator is allowed; clinical diagnosis of uveal melanoma is often made by an ophthalmologist, not by tissue diagnosis; if an ophthalmologist diagnosed and treated a patient for uveal melanoma in the past, it is sufficient for a clinical diagnosis
Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 20 mm (>= 2 cm) with conventional techniques or as >= 10 mm (>= 1 cm) with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam
The study will be limited to patients who are chemotherapy naive; patients may have received prior systemic or liver-directed local therapies for advanced uveal melanoma as long as those treatments do not involve chemotherapy; this includes, but is not limited to: immunotherapy, targeted therapy, transarterial embolization, radiofrequency ablation, or cryoablation; treatment must be completed at least 28 days prior to initiation of study therapy; radiation therapy is also allowed and must be completed at least 28 days prior to initiation of study therapy; lesions treated via radiation or liver-directed therapy may not be used as target lesions unless they demonstrate growth over a minimum of 3 months on subsequent imaging
All prior treatment-related toxicities must be Common Terminology Criteria for Adverse Events (CTCAE) version (V) 5 grade =< 1 (except alopecia); certain exceptions apply, such as immunotherapy-induced hypothyroidism or adrenal insufficiency or panhypopituitarism requiring stable doses of hormone replacement or rash from prior therapy
Eastern Cooperative Oncology Group (ECOG) performance status =< 2
Life expectancy of greater than 3 months
Leukocytes >= 3,000/uL
Absolute neutrophil count >= 1,500/uL
Platelets >= 100,000/uL
Total bilirubin =< 1.5 x institutional upper limit of normal
Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal; =< 5 x institutional upper limit of normal if liver metastasis present
Creatinine =< institutional upper limit of normal OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
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, for the duration of study participation, and for 4 months after last CDX-011 (glembatumumab vedotin) dose; women of child-bearing potential must have a negative serum pregnancy test within 14 days prior to start of protocol treatment; 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 and women 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 glembatumumab vedotin administration
Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

Patients with a history of another malignancy except for those who have been disease-free for 2 years; patients with a history of definitively treated non-melanoma skin cancer or squamous cell carcinoma of the cervix are eligible; patients with definitively treated in-situ cancers are eligible, regardless of timeframe
Patients with neuropathy > grade 1
Patients who are receiving any other investigational agents; if the patient received a previous investigational or other agent or treatment, a washout period of 4 weeks is required
Patients receiving any medications or substances that are substrates of cytochrome P450 family 3, subfamily A, polypeptide 4 (CYP3A4) will be closely monitored for toxicity; as part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
Human immunodeficiency virus (HIV)-positive patients on antiretroviral medications that are CYP3A4 substrates will be closely monitored; HIV-positive patients will be excluded if they have a cluster of differentiation 4 (CD4) count < 200
Pregnant or nursing women
Patients who have previously received CDX-011 (glembatumumab vedotin) or other monomethyl auristatin E (MMAE)-containing agents
Patients with a history of allergic reactions attributed to compounds of similar composition to dolastatin or auristatin (e.g. Auristatin PHE, Auristatin PE, and symplostatin)

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (glembatumumab vedotin)	Glembatumumab Vedotin	Patients receive glembatumumab vedotin IV over 90 minutes every 3 weeks in the absence of disease progression or unacceptable toxicity.
Treatment (glembatumumab vedotin)	Laboratory Biomarker Analysis	Patients receive glembatumumab vedotin IV over 90 minutes every 3 weeks in the absence of disease progression or unacceptable toxicity.
Treatment (glembatumumab vedotin)	Pharmacological Study	Patients receive glembatumumab vedotin IV over 90 minutes every 3 weeks in the absence of disease progression or unacceptable toxicity.

Primary Outcome Measures

Name	Time	Method
Overall Response Rate Using Response Evaluation Criteria in Solid Tumors Version 1.1	From date of treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years and 10 months	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI and/or CT: Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for a Partial Response nor sufficient increase to qualify for Progression of Disease (PD); PD, 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Complete Response (CR), Disappearance of all target lesions

Secondary Outcome Measures

Name	Time	Method
The Number of Participants With Change in Glycoprotein NMB Expression on Tumor Tissue Via Immunohistochemistry	Baseline to up to 21 days	Target protein expression change from baseline to after 1 cycle of treatment.
Progression-free Survival	From consent to time of progression or death, whichever occurs first, assessed up to 2 years and 10 months	Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Number of Participants With Grade 3-4 Adverse Events According to the National Cancer Institute Common Toxicity Criteria Version 4.0	through 30 days post-treatment, up to 2 years and 10 months	Toxicity will be reported by type, frequency, and severity. Only adverse events toxicity with grade 3-4 severity.
Overall Survival	From consent to time of progression or death, whichever occurs first, assessed up to 2 years and 10 months	Overall survival as measured from time of enrollment to time of death due to any cause.

Trial Locations

Locations (25): University of Chicago Medicine-Orland Park
🇺🇸
Orland Park, Illinois, United States
University of Kansas Clinical Research Center
🇺🇸
Fairway, Kansas, United States
UT Southwestern/Simmons Cancer Center-Dallas
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Dallas, Texas, United States
Mayo Clinic Hospital
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Phoenix, Arizona, United States
University of Colorado Hospital
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Aurora, Colorado, United States
Northwestern University
🇺🇸
Chicago, Illinois, United States
University of Chicago Comprehensive Cancer Center
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Chicago, Illinois, United States
Massachusetts General Hospital Cancer Center
🇺🇸
Boston, Massachusetts, United States
Brigham and Women's Hospital
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Boston, Massachusetts, United States
Beth Israel Deaconess Medical Center
🇺🇸
Boston, Massachusetts, United States
Mayo Clinic
🇺🇸
Rochester, Minnesota, United States
Ohio State University Comprehensive Cancer Center
🇺🇸
Columbus, Ohio, United States
University of Pennsylvania/Abramson Cancer Center
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Philadelphia, Pennsylvania, United States
M D Anderson Cancer Center
🇺🇸
Houston, Texas, United States
Huntsman Cancer Institute/University of Utah
🇺🇸
Salt Lake City, Utah, United States
Mayo Clinic in Arizona
🇺🇸
Scottsdale, Arizona, United States
Mayo Clinic in Florida
🇺🇸
Jacksonville, Florida, United States
University of Kansas Cancer Center
🇺🇸
Kansas City, Kansas, United States
Dana-Farber Cancer Institute
🇺🇸
Boston, Massachusetts, United States
Barnes-Jewish Hospital
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Saint Louis, Missouri, United States
Roswell Park Cancer Institute
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Buffalo, New York, United States
Washington University School of Medicine
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Saint Louis, Missouri, United States
Penn State Milton S Hershey Medical Center
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Hershey, Pennsylvania, United States
UC Comprehensive Cancer Center at Silver Cross
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New Lenox, Illinois, United States
Dartmouth Hitchcock Medical Center
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Lebanon, New Hampshire, United States