Study of Patients With Stage IV Malignant Melanoma Using PS-341 (Bortezomib, Velcade) and Interferon-alpha-2b in Malignant Melanoma

NCT01462773 | Completed Phase 1 Results DMC

• 2 other identifiers: OSU-04105NCI-2011-03174
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine the safety, tolerability and dose limiting toxicities (DLTs) of VELCADE when administered in combination with interferon-alpha-2b (IFN-α-2b) to patients with metastatic malignant melanoma.

Conditions

Melanoma

Keywords

malignant; melanoma

Outcome Measures

Primary Outcomes (1)

• Determine Dose Limiting Toxicities (DLTs) of VELCADE When Administered in Combination With IFN-α-2b to Patients With Metastatic Malignant Melanoma.

  A standard method for the design of this study. Initially, three patients will be treated at a starting dose of VELCADE (1.0 mg/m2). If one of the three patients demonstrates a DLT, then an additional 3 patients will be treated at that dose level. If only one of the six show DLT, then the next cohort of three patients will be entered at the next dose level (1.3 mg/m2). If two or more of the six demonstrate DLT, no further patients will be treated at that dose level. The highest dose level at which less than 2 patients experienced DLT will be expanded to six patients.

  up to 25 weeks or until disease progression

Secondary Outcomes (1)

• Document Any Objective Anti-tumor Responses and Time to Tumor Progression That May Occur in Response to This Treatment Regimen.

  up to 25 weeks

Study Arms (1)

Treatment (enzyme inhibitor, interferon therapy)

EXPERIMENTAL

Patients receive bortezomib IV over 3-5 seconds on days 1, 8, 15, and 22 and recombinant interferon alfa-2b SC on days 1, 3, and 5 (days 1 and 3 only in week 4 course 1) of weeks 1-4. Treatment repeats every 5 weeks for 5 courses in the absence of disease progression or unacceptable toxicity.

Drug: Bortezomib; Drug: Interferon Alfa-2b

Interventions

Bortezomib DRUG

VELCADE (1.0 mg/m2, 1.3 mg/m2, or 1.6 mg/m2 IV based on patient cohort). After three patients have received 5 weeks of therapy (1 cycle) at the initial dose of VELCADE (1.0 mg/m2, Cohort 1) with no dose limiting toxicity, the dose will be raised to 1.3 mg/m2 for the next cohort of three patients. If this dose level is well-tolerated in three consecutive patients, the dose of VELCADE will be raised to 1.6 mg/m2.

Also known as: VELCADE®

Treatment (enzyme inhibitor, interferon therapy)

Interferon Alfa-2b DRUG

I = IFN-α-2b (INTRON A): 5 million units (MU)/m2 SC. INTRON A (5MU/m2) will be administered subcutaneously on Days 1, 3 and 5 of Week 0. During Cycle I, INTRON A will be administered on Days 1, 3 and 5 of Weeks 1-3 of and on Days 1 and 3 of Week 4 to allow for surgical biopsy on Day 5. During Cycles II-V, IFN-α will be administered on Days 1, 3 and 5 of Weeks 1-4. To assess the toxicity profile of IFN-α-2b alone, no VELCADE will be administered during Week 0.

Also known as: IFN-α-2b

Treatment (enzyme inhibitor, interferon therapy)

Eligibility Criteria

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

You may qualify if:

• must have histological or cytological diagnosis of cutaneous melanoma and clinical evidence of metastatic, non-resectable regional lymphatic, or extensive in transit recurrent disease. Patients who have had resected metastases will also be eligible provided they have measurable disease.
• have measurable disease. Measurable disease is defined as the presence of at least one measurable lesion.
• ECOG performance status ≤ 2 (Karnofsky ≥ 60%).
• Female subjects must be either surgically sterilized or willing to use an acceptable method of birth control (ie, a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study. Male subjects must agree to use an acceptable method for contraception for the duration of the study.
• Patients must have normal organ and marrow function.
• Prior Therapy: Patients with an ECOG performance status of ≤ 2 will be eligible for this protocol regardless of the number of prior treatments provided they have recovered from the reversible effects of prior therapy. Patients are permitted to have received therapy with adjuvant IFN-α2b, if it was completed \> 6 months prior to enrollment in the current study.
• Patients with brain metastases are eligible for entry into the study, but must have received definitive therapy consisting of external beam radiation therapy, gamma knife therapy or surgical resection and be clinically stable. Four weeks after the definitive therapy is completed, repeat MRI or CT scans must demonstrate stabilization of disease, and there must be no requirement for Decadron. If the patient does not have brain metastases, then only one brain CT or MRI is required prior to enrollment on study.

You may not qualify if:

• Patient has a platelet count of \< 100 × 109/L within 14 days before enrollment.
• Patient has an absolute neutrophil count of \< 1.0 x 109/L within 14 days before enrollment.
• Patient has a calculated or measured creatinine clearance of \< 30 mL/minute within 14 days before enrollment.
• Patient has history of significant brain metastases or other clinically significant central nervous system disease.
• Patient has ≥Grade 2 peripheral neuropathy within 14 days before enrollment.
• Patient has hypersensitivity to bortezomib, boron or mannitol.
• Patients with evidence of proteinuria on urinalysis.
• Female subject is pregnant or breast-feeding.
• Received other investigational drugs with 14 days before enrollment.
• Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
• History of serious psychiatric illness that might be exacerbated by IFN-α-2b.

Sponsors & Collaborators

• Ohio State University Comprehensive Cancer Center: lead

Study Sites (1)

Ohio State University

Columbus, Ohio, 43210, United States

Location

Related Publications (1)

• Markowitz J, Luedke EA, Grignol VP, Hade EM, Paul BK, Mundy-Bosse BL, Brooks TR, Dao TV, Kondalasula SV, Lesinski GB, Olencki T, Kendra KL, Carson WE 3rd. A phase I trial of bortezomib and interferon-alpha-2b in metastatic melanoma. J Immunother. 2014 Jan;37(1):55-62. doi: 10.1097/CJI.0000000000000009.

  PMID: 24316557 RESULT

Related Links

• Jamesline

MeSH Terms

Conditions

Melanoma

Interventions

Bortezomib; Interferon alpha-2

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)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Interferon-alpha; Interferon Type I; Interferons; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Results Point of Contact

• Title: William Carson
• Organization: The Ohio State University Comprehensive Cancer Center

william.carson@osumc.edu

614-293-6306

Study Officials

• William Carson, MD

  Ohio State University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 19, 2011
• First Posted: October 31, 2011
• Study Start: January 1, 2006
• Primary Completion: October 1, 2010
• Study Completion: April 1, 2013
• Last Updated: January 13, 2015
• Results First Posted: December 30, 2014

Record last verified: 2014-12

Locations

US (1)