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

NCT02363283 | Completed Phase 2 Results

• 5 other identifiers: NCI-2015-00159NCI98559855N01CM00039UM1CA186712
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 25

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.

Conditions

Recurrent Uveal Melanoma; Stage IV Uveal Melanoma AJCC v7

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate Using Response Evaluation Criteria in Solid Tumors Version 1.1

  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

  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

Secondary Outcomes (4)

• The Number of Participants With Change in Glycoprotein NMB Expression on Tumor Tissue Via Immunohistochemistry

  Baseline to up to 21 days

• Progression-free Survival

  From consent to time of progression or death, whichever occurs first, assessed up to 2 years and 10 months

• 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

• Overall Survival

  From consent to time of progression or death, whichever occurs first, assessed up to 2 years and 10 months

Study Arms (1)

Treatment (glembatumumab vedotin)

EXPERIMENTAL

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

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

Interventions

Glembatumumab Vedotin DRUG

Given IV

Also known as: Antibody-Drug Conjugate CR011-vcMMAE, CDX-011, CR011-vcMMAE, CR011-vcMMAE Immunotoxin

Treatment (glembatumumab vedotin)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (glembatumumab vedotin)

Pharmacological Study OTHER

Correlative studies

Treatment (glembatumumab vedotin)

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (25)

Mayo Clinic Hospital

Phoenix, Arizona, 85054, United States

Location

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

Location

University of Colorado Hospital

Aurora, Colorado, 80045, United States

Location

Mayo Clinic in Florida

Jacksonville, Florida, 32224-9980, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

Location

UC Comprehensive Cancer Center at Silver Cross

New Lenox, Illinois, 60451, United States

Location

University of Chicago Medicine-Orland Park

Orland Park, Illinois, 60462, United States

Location

University of Kansas Clinical Research Center

Fairway, Kansas, 66205, United States

Location

University of Kansas Cancer Center

Kansas City, Kansas, 66160, United States

Location

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02114, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Barnes-Jewish Hospital

St Louis, Missouri, 63110, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Penn State Milton S Hershey Medical Center

Hershey, Pennsylvania, 17033-0850, United States

Location

University of Pennsylvania/Abramson Cancer Center

Philadelphia, Pennsylvania, 19104, United States

Location

UT Southwestern/Simmons Cancer Center-Dallas

Dallas, Texas, 75390, United States

Location

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, 84112, United States

Location

MeSH Terms

Conditions

Uveal Melanoma

Interventions

glembatumumab vedotin; CR011-vcMMAE

Condition Hierarchy (Ancestors)

Melanoma; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Uveal Neoplasms; Eye Neoplasms; Neoplasms by Site; Eye Diseases; Uveal Diseases

Results Point of Contact

• Title: Dr. Sapna Pradyuman Patel,MD/ Melanoma Medical Oncology
• Organization: UT MD Anderson Cancer Center

SPPatel@mdanderson.org

713-792-2921

Study Officials

• Sapna Patel

  University of Texas MD Anderson Cancer Center LAO

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 13, 2015
• First Posted: February 16, 2015
• Study Start: September 16, 2015
• Primary Completion: July 2, 2018
• Study Completion: July 2, 2018
• Last Updated: August 21, 2020
• Results First Posted: August 21, 2020

Record last verified: 2020-07

Locations

US (25)