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

December 30, 2014 updated by: William Carson, Ohio State University Comprehensive Cancer Center

A Phase I Study of PS-341 (Bortezomib, Velcade) and Interferon-alpha-2b in Malignant Melanoma.

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
16

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Ohio
      • Columbus, Ohio, United States, 43210
        • Ohio State University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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:

  • Patients meeting any of the following exclusion criteria are not to be enrolled in the study.

    • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: 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.
Drug: 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.
Other Names:
  • VELCADE®
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.
Other Names:
  • IFN-α-2b

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Determine Dose Limiting Toxicities (DLTs) of VELCADE When Administered in Combination With IFN-α-2b to Patients With Metastatic Malignant Melanoma.
Time Frame: up to 25 weeks or until disease progression
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Document Any Objective Anti-tumor Responses and Time to Tumor Progression That May Occur in Response to This Treatment Regimen.
Time Frame: up to 25 weeks
  • 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.
up to 25 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Ohio State University Comprehensive Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 2006

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 1, 2010

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 1, 2013

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 19, 2011

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 28, 2011

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 31, 2011

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 13, 2015

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 30, 2014

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • OSU-04105
  • NCI-2011-03174 (Registry Identifier: Clinical Trials Reporting Program (CTRP))

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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