Ibrutinib in Treating Patients With Refractory Metastatic Cutaneous Melanoma

NCT02581930 | Active Not Recruiting Phase 2 Results

• 14 other identifiers: NCI-2015-01744NCI99229922UM1CA186644UM1CA186686UM1CA186688UM1CA186689UM1CA186690UM1CA186691UM1CA186704UM1CA186709UM1CA186712UM1CA186716UM1CA186717
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 13

Brief Summary

This phase II trial studies how well ibrutinib works in treating patients with stage IV melanoma of the skin that has not responded to previous treatment. Ibrutinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Conditions

Metastatic Melanoma; Recurrent Cutaneous Melanoma; Stage IV Cutaneous Melanoma AJCC v6 and v7

Outcome Measures

Primary Outcomes (1)

• Number of Subjects With Antitumor Response as Evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) Criteria 1.1

  Antitumor response defined as the sum of complete response (CR) and partial response (PR). CR is the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm (\<1 cm). PR is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

  1 year

Secondary Outcomes (2)

• Progression Free Survival

  1 year

• Overall Survival

  Duration of time from day 1 of treatment to death as a result of any cause, assessed up to 1 year

Other Outcomes (3)

• Expression Levels of ITK and Putative Targets of Ibrutinib (e.g. Tec, ErbB4, Hck, Yes, BTK)

  Up to 1 year

• Change in Th1, Th2, and Various Immune Regulatory Cell Populations in Peripheral Blood Mononuclear Cells and Assessed by Flow Cytometry

  Baseline up to 1 year

• Pharmacokinetic Analysis on Ibrutinib Concentrations in Plasma Using WinNonlin

  Pre-dose on days 1 and day 8 of course 1 and post-dose, 0.5, 1, 2, 4, 6, and 24 hours on day 8 of course 1

Study Arms (1)

Treatment (ibrutinib)

EXPERIMENTAL

Patients receive ibrutinib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Ibrutinib; Other: Laboratory Biomarker Analysis; Other: Pharmacogenomic Study; Other: Pharmacological Study

Interventions

Ibrutinib DRUG

Given PO

Also known as: BTK Inhibitor PCI-32765, CRA 032765, CRA-032765, CRA032765, Imbruvica, PCI 32765, PCI-32765, PCI32765

Treatment (ibrutinib)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (ibrutinib)

Pharmacogenomic Study OTHER

Correlative studies

Also known as: PHARMACOGENOMIC

Treatment (ibrutinib)

Pharmacological Study OTHER

Correlative studies

Treatment (ibrutinib)

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed melanoma of cutaneous primary; metastatic melanoma from unknown primary are allowed
• 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 \>= 10 mm (\>= 1 cm) with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam
• Stage IV disease
• If BRAFV600-mutant, documented refractory disease to at least one BRAF inhibitor (dabrafenib or vemurafenib) and/or a MEK inhibitor (trametinib or cobimetinib), defined as progression of measurable disease as per Response Evaluation Criteria in Solid Tumors (RECIST) criteria while on treatment; subjects with MAPK inhibitor-intolerance are eligible if they meet criteria
• Documented disease refractory to at least one PD1/PD-L1 inhibitor, defined as disease progression following at least 2 infusions of the same drug; radiographic disease progression will be documented by the institutional radiologist based on any radiographic evidence (magnetic resonance imaging \[MRI\], computed tomography \[CT\], positron emission tomography \[PET\], or other modalities, etc.) of disease progression on two separate radiographic scans assessment obtained at least 4 weeks apart; this minimum 4-week interval is required to define PD-1 inhibitor resistance based on imaging; alternatively, clinical disease progression may be documented on examination by the treating investigator
• Prior treatment-related toxicity resolved to =\< grade 1 or baseline with the exception of alopecia and permanent grade =\< 2 toxicities related to prior immune checkpoint inhibitor treatment (e.g. PD-1/PD-L1, CTLA-4, CD40, LAG3) treatment with the review and approval by the lead principal investigator (PI)
• Prior radiation allowed (no restriction on amount); measurable lesion(s) may not have been previously irradiated
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
• Life expectancy of greater than 3 months
• Hemoglobin \>= 9.0 g/dL
• Absolute neutrophil count (ANC) \> 1,500/uL
• Platelets \> 100,000/uL
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2 x upper limit of normal (ULN); =\< 5 x ULN, if liver metastasis
• Total bilirubin =\< 1.5 x ULN unless Gilbert's syndrome of disease infiltration of the liver is present
• Creatinine clearance estimated glomerular filtration rate (GFR) \>= 30 mL/min/1.73 m\^2 (Cockcroft-Gault)

You may not qualify if:

• Patients with melanoma of mucosal or ocular primary
• Patients who have had chemotherapy or immunotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) or radiotherapy within 2 weeks prior to cycle 1 day 1; patients who have had tyrosine kinase inhibitors (such as Braf or MEK inhibitors) within 15 days of cycle 1 day 1
• Patients who are receiving any other biologic, cytotoxic or investigational agents
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to ibrutinib (difficulty breathing, lip swelling, itching or rash)
• 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
• Pregnant and breastfeeding women are excluded from this study; breastfeeding should be discontinued if the mother is treated with ibrutinib
• Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are eligible; unless the patient's cluster of differentiation (CD)4+ count is below the institutional lower limit of normal
• Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenic purpura (ITP) resulting in (or as evidenced by) declining platelet or hemoglobin (Hgb) levels within the 4 weeks prior to first dose of study drug
• Presence of transfusion-dependent thrombocytopenia
• Need for daily corticosteroids at high doses (prednisone \>= 20 mg daily, or an equivalent) is prohibited from 28 days prior to first dose and during treatment with ibrutinib; brief (up to 7 days) and episodic use of systemic corticosteroids for other general conditions (e.g. pre-medication for radiographic imaging due to intravenous \[IV\] contrast allergy, chronic obstructive pulmonary disease \[COPD\] exacerbation, poison ivy, etc.) is allowed
• Prior exposure to ibrutinib or other ITK inhibitors
• History of prior malignancy, with the exception of the following:
• Non-melanoma skin cancers, non-invasive bladder cancer, and carcinoma in situ of the cervix
• Prostate cancer not under active systemic treatment other than hormonal therapy and with documented undetectable prostate-specific antigen (PSA) (\< 0.2 ng/mL)
• Chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) provided patient has isolated lymphocytosis (Rai stage O), and does not require systemic treatment (for "B" symptoms, Richter's transformation, lymphocyte doubling time \[\< 6 months\], lymphadenopathy or hepatosplenomegaly)

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (13)

Los Angeles General Medical Center

Los Angeles, California, 90033, United States

Location

USC / Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

UCHealth University of Colorado Hospital

Aurora, Colorado, 80045, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

University of Kentucky/Markey Cancer Center

Lexington, Kentucky, 40536, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Case Western Reserve University

Cleveland, Ohio, 44106, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

University of Virginia Cancer Center

Charlottesville, Virginia, 22908, United States

Location

University of Wisconsin Carbone Cancer Center - University Hospital

Madison, Wisconsin, 53792, United States

Location

Related Publications (1)

• Moschos SJ, Eroglu Z, Khushalani NI, Kendra KL, Ansstas G, In GK, Wang P, Liu G, Collichio FA, Googe PB, Carson CC, McKinnon K, Wang HH, Nikolaishvilli-Feinberg N, Ivanova A, Arrowood CC, Garrett-Mead N, Conway KC, Edmiston SN, Ollila DW, Serody JS, Thomas NE, Ivy SP, Agrawal L, Dees EC, Abbruzzese JL. Targeting the IL-2 inducible kinase in melanoma; a phase 2 study of ibrutinib in systemic treatment-refractory distant metastatic cutaneous melanoma: preclinical rationale, biology, and clinical activity (NCI9922). Melanoma Res. 2021 Apr 1;31(2):162-172. doi: 10.1097/CMR.0000000000000726.

  PMID: 33661190 DERIVED

MeSH Terms

Conditions

Melanoma

Interventions

ibrutinib; Pharmacogenomic Testing

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

Intervention Hierarchy (Ancestors)

Genetic Testing; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Genetic Techniques; Genetic Services; Health Services; Health Care Facilities Workforce and Services; Diagnostic Services; Preventive Health Services

Results Point of Contact

• Title: Dr. Stergios Moschos
• Organization: University of North Carolina at Chapel Hill

stergios_moschos@med.unc.edu

919-843-7713

Study Officials

• Stergios J Moschos

  Duke University - Duke Cancer Institute 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: October 20, 2015
• First Posted: October 21, 2015
• Study Start: August 17, 2016
• Primary Completion: February 10, 2018
• Study Completion (Estimated): March 4, 2027
• Last Updated: April 30, 2026
• Results First Posted: June 18, 2019

Record last verified: 2026-03

Locations

US (13)