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

NCT ID: NCT02363283

Last Updated: 2020-08-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 37 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-09-16
• Study Completion Date: 2018-07-02

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.

Conditions

Recurrent Uveal Melanoma; Stage IV Uveal Melanoma AJCC v7

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (glembatumumab vedotin)

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

Group Type: EXPERIMENTAL

Glembatumumab Vedotin

Intervention Type: DRUG

Given IV

Laboratory Biomarker Analysis

Intervention Type: OTHER

Correlative studies

Pharmacological Study

Intervention Type: OTHER

Correlative studies

Interventions

Glembatumumab Vedotin

Given IV

Intervention Type: DRUG

Laboratory Biomarker Analysis

Correlative studies

Intervention Type: OTHER

Pharmacological Study

Correlative studies

Intervention Type: OTHER

Other Intervention Names

Antibody-Drug Conjugate CR011-vcMMAE; CDX-011; CR011-vcMMAE; CR011-vcMMAE Immunotoxin

Eligibility Criteria

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sapna Patel

Role: PRINCIPAL_INVESTIGATOR

University of Texas MD Anderson Cancer Center LAO

Locations

Mayo Clinic Hospital

Phoenix, Arizona, United States

Mayo Clinic in Arizona

Scottsdale, Arizona, United States

University of Colorado Hospital

Aurora, Colorado, United States

Mayo Clinic in Florida

Jacksonville, Florida, United States

Northwestern University

Chicago, Illinois, United States

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, United States

UC Comprehensive Cancer Center at Silver Cross

New Lenox, Illinois, United States

University of Chicago Medicine-Orland Park

Orland Park, Illinois, United States

University of Kansas Clinical Research Center

Fairway, Kansas, United States

University of Kansas Cancer Center

Kansas City, Kansas, United States

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, United States

Brigham and Women's Hospital

Boston, Massachusetts, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Mayo Clinic

Rochester, Minnesota, United States

Barnes-Jewish Hospital

St Louis, Missouri, United States

Washington University School of Medicine

St Louis, Missouri, United States

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, United States

Roswell Park Cancer Institute

Buffalo, New York, United States

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States

Penn State Milton S Hershey Medical Center

Hershey, Pennsylvania, United States

University of Pennsylvania/Abramson Cancer Center

Philadelphia, Pennsylvania, United States

UT Southwestern/Simmons Cancer Center-Dallas

Dallas, Texas, United States

M D Anderson Cancer Center

Houston, Texas, United States

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

NCI-2015-00159

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCI9855

Identifier Type: -

Identifier Source: secondary_id

9855

Identifier Type: OTHER

Identifier Source: secondary_id

9855

Identifier Type: OTHER

Identifier Source: secondary_id

N01CM00039

Identifier Type: NIH

Identifier Source: secondary_id

View Link

UM1CA186712

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2015-00159

Identifier Type: -

Identifier Source: org_study_id