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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
William Carson, Ohio State University Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT01462773
First received: October 19, 2011
Last updated: August 16, 2013
Last verified: August 2013
  Purpose

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.


Condition Intervention Phase
Melanoma
Drug: Bortezomib
Drug: Interferon Alfa-2b
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of PS-341 (Bortezomib, Velcade) and Interferon-alpha-2b in Malignant Melanoma.

Resource links provided by NLM:


Further study details as provided by Ohio State University Comprehensive Cancer Center:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
    • 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.


Enrollment: 16
Study Start Date: January 2006
Estimated Study Completion Date: December 2013
Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Bortezomib
VELCADE will be initiated on Day 1 of Cycle 1. In the absence of clinically significant adverse events, VELCADE will be administered once a week on Day 1, 8, 15 and 22 of each Cycle.
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 Name: VELCADE®
Experimental: Interferon Alfa-2b
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. Treatment will continue for a total of 5 Cycles or until toxicity or disease progression is evident.
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 Name: IFN-α-2b

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.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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:

  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01462773

Locations
United States, Ohio
Ohio State University
Columbus, Ohio, United States, 43210
Sponsors and Collaborators
Ohio State University Comprehensive Cancer Center
Investigators
Principal Investigator: William Carson, MD Ohio State University
  More Information

Additional Information:
No publications provided

Responsible Party: William Carson, Principal Investigator, Ohio State University Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT01462773     History of Changes
Other Study ID Numbers: OSU-04105, NCI-2011-03174
Study First Received: October 19, 2011
Last Updated: August 16, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Ohio State University Comprehensive Cancer Center:
malignant
melanoma

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Bortezomib
Interferons
Interferon-alpha
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antiviral Agents
Anti-Infective Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 16, 2014