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

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ClinicalTrials.gov Identifier: NCT02363283
Recruitment Status : Completed
First Posted : February 16, 2015
Last Update Posted : October 17, 2018
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Recurrent Uveal Melanoma Stage IV Uveal Melanoma AJCC v7 Drug: Glembatumumab Vedotin Other: Laboratory Biomarker Analysis Other: Pharmacological Study Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 37 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Study of CDX-011 (Glembatumumab Vedotin) for Metastatic Uveal Melanoma
Actual Study Start Date : September 16, 2015
Actual Primary Completion Date : July 2, 2018
Actual Study Completion Date : July 2, 2018


Arm Intervention/treatment
Experimental: Treatment (glembatumumab vedotin)
Patients receive glembatumumab vedotin IV over 90 minutes every 3 weeks in the absence of disease progression or unacceptable toxicity.
Drug: Glembatumumab Vedotin
Given IV
Other Names:
  • Antibody-Drug Conjugate CR011-vcMMAE
  • CDX-011
  • CR011-vcMMAE
  • CR011-vcMMAE Immunotoxin

Other: Laboratory Biomarker Analysis
Correlative studies

Other: Pharmacological Study
Correlative studies




Primary Outcome Measures :
  1. Overall response rate using Response Evaluation Criteria in Solid Tumors version 1.1 [ Time Frame: Up to 30 days post-treatment ]

Secondary Outcome Measures :
  1. Change in glycoprotein NMB expression on tumor tissue via immunohistochemistry [ Time Frame: Baseline to up to 21 days on study ]
    Changes in percentage of glycoprotein NMB -positive tumor cells will be reported and descriptive statistics will be used to further report staining intensity and frequency in baseline and on-treatment tumor samples.

  2. Progression-free survival [ Time Frame: From start of treatment to time of progression or death, whichever occurs first, assessed up to 30 days ]
    Progression-free survival curves will be calculated using the method of Kaplan-Meier. Median progression-free survival will be reported with 95% confidence intervals.

  3. Overall survival [ Time Frame: Up to 30 days post-treatment ]
    Overall survival curves will be calculated using the method of Kaplan-Meier. Median overall survival will be reported with 95% confidence intervals.

  4. Incidence of adverse events according to the National Cancer Institute Common Toxicity Criteria version 5.0 [ Time Frame: Up to 30 days post-treatment ]
    Toxicity will be reported by type, frequency, and severity.


Other Outcome Measures:
  1. Anti-tumor immunophenotype of patients receiving glembatumumab vedotin [ Time Frame: Up to 30 days post-treatment ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02363283


  Show 25 Study Locations
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Sapna Patel University of Texas MD Anderson Cancer Center LAO
  Study Documents (Full-Text)

Documents provided by National Cancer Institute (NCI):

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Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT02363283     History of Changes
Other Study ID Numbers: NCI-2015-00159
NCI-2015-00159 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
NCI9855
9855 ( Other Identifier: University of Texas MD Anderson Cancer Center LAO )
9855 ( Other Identifier: CTEP )
N01CM00039 ( U.S. NIH Grant/Contract )
UM1CA186712 ( U.S. NIH Grant/Contract )
First Posted: February 16, 2015    Key Record Dates
Last Update Posted: October 17, 2018
Last Verified: October 2018

Additional relevant MeSH terms:
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Melanoma
Uveal Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Eye Neoplasms
Neoplasms by Site
Eye Diseases
Uveal Diseases
Immunoconjugates
Antibodies, Monoclonal
Glembatumumab vedotin
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Immunological
Antineoplastic Agents