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

NCT ID: NCT01462773

Last Updated: 2015-01-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-01-31
• Study Completion Date: 2013-04-30

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.

Detailed Description

The primary objective of this study is to:

• Determine the safety, tolerability and DLTs of VELCADE when administered in combination with interferon-alpha-2b (IFN-α-2b) to patients with metastatic malignant melanoma.

The secondary objectives of this study are to:

• Document any objective anti-tumor responses that may occur in response to this treatment regimen.
• Document the time to tumor progression in patients receiving this treatment regimen.
• Measure levels of the cell cycle proteins p21 and p27 in PBMCs and tumor biopsies obtained pre-study and during week 4 of Cycle 1 (Day 26).
• Conduct histologic evaluations of microvessel density, tumor apoptosis and lymphocytic infiltrates within tumor biopsies obtained pre- and post-study.
• Measure plasma levels of bFGF and VEGF over the course of the study.
• Monitor the effects of proteasome inhibition on the biological activity of IFN-α within immune cells by measuring Jak-STAT signal transduction in patient PBMCs.

Conditions

Melanoma

Study Design

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

Study Groups

Treatment (enzyme inhibitor, interferon therapy)

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.

Group Type: EXPERIMENTAL

Bortezomib

Intervention Type: 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.

Interferon Alfa-2b

Intervention Type: 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.

Interventions

Bortezomib

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.

Intervention Type: DRUG

Interferon Alfa-2b

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.

Intervention Type: DRUG

Other Intervention Names

VELCADE®; IFN-α-2b

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

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

Sponsors

Ohio State University Comprehensive Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

William Carson

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

William Carson, MD

Role: PRINCIPAL_INVESTIGATOR

Ohio State University

Locations

Ohio State University

Columbus, Ohio, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 24316557 (View on PubMed)

Related Links

http://cancer.osu.edu

Jamesline

Other Identifiers

NCI-2011-03174

Identifier Type: REGISTRY

Identifier Source: secondary_id

OSU-04105

Identifier Type: -

Identifier Source: org_study_id