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PS-341 in Treating Patients With Metastatic Malignant Melanoma

Primary Purpose

Recurrent Melanoma, Stage IV Melanoma

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
bortezomib
laboratory biomarker analysis
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Recurrent Melanoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Histologically or cytologically confirmed metastatic malignant melanoma Measurable disease defined as at least one lesion whose longest diameter can be accurately measured as >= 2.0 cm Absolute neutrophil count (ANC) >= 1500/uL PLT >= 100,000/uL Total bilirubin =< 2.5 x institutional upper normal limit (UNL) AST =< 2.5 x UNL Creatinine =< 1.5 x UNL or calculated creatinine clearance > 60 mL/min/1.73 m^2 for patients with creatinine levels > 1.5 x UNL using the Cockcroft-Gault formula Life expectancy of >= 3 months ECOG performance status 0 or 1 Capable of understanding the investigational nature, potential risks and benefits of the study and willing to sign the written informed consent document Exclusion Criteria: Any of the following: Any prior chemotherapy Immunotherapy =< 4 weeks prior to study entry Biologic therapy =< 4 weeks prior to study entry Radiation therapy =< 4 weeks prior to study entry Failure to fully recover from adverse effects of prior therapies regardless of interval since last treatment Other concurrent chemotherapy, immunotherapy, radiotherapy, or any other therapy or supportive care considered investigational Known brain metastases requiring active treatment; NOTE: these patients are excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events History of allergic reactions attributed to compounds of similar chemical or biologic composition to PS-341 Uncontrolled intercurrent illness including, but not limited to: Ongoing or active infection Symptomatic congestive heart failure Unstable angina pectoris, cardiac arrhythmia Psychiatric illness that would limit compliance with study requirements HIV-positive patients receiving combination anti-retroviral therapy; NOTE: patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy; these patients are excluded from the study because of possible pharmacokinetic interactions with PS-341; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated Any of the following: Pregnant women Nursing women Men or women of childbearing potential who are unwilling to employ adequate contraception (condoms, diaphragm, birth control pills, injections, subcutaneous implants, intrauterine device [IUD], abstinence, etc.) NOTE: this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown Only non-measurable disease, including lesions not clearly measurable in one dimension, small lesions (longest diameter < 20 mm), and truly non-measurable lesions, which include the following as per RECIST criteria: Bone lesions Leptomeningeal disease Ascites Pleural/pericardial effusion Inflammatory breast disease Lymphangitis cutis/pulmonis Abdominal masses that are not confirmed and followed by imaging techniques Cystic lesions

Sites / Locations

  • Mayo Clinic

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (bortezomib)

Arm Description

Patients receive PS-341 IV over 3-5 seconds on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Outcomes

Primary Outcome Measures

Proportion of patients who are progression-free
Confidence intervals for the true success proportion will be calculated.

Secondary Outcome Measures

Objective response is defined by the Response Evaluation Criteria in Solid Tumors (RECIST) in terms of tumor/lesion size and change
Overall survival
The distribution of survival time will be estimated using the method of Kaplan-Meier.

Full Information

First Posted
September 13, 2001
Last Updated
January 15, 2013
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00024011
Brief Title
PS-341 in Treating Patients With Metastatic Malignant Melanoma
Official Title
A Phase II Study of PS-341 in the Treatment of Metastatic Malignant Melanoma
Study Type
Interventional

2. Study Status

Record Verification Date
January 2013
Overall Recruitment Status
Completed
Study Start Date
July 2001 (undefined)
Primary Completion Date
September 2006 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief Summary
Phase II trial to study the effectiveness of PS-341 in treating patients who have metastatic malignant melanoma. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die
Detailed Description
OBJECTIVES: I. Determine the progression-free survival at 18 weeks and overall survival of patients with metastatic malignant melanoma treated with PS-341. II. Determine the objective response rate of patients treated with this drug. III. Correlate p27 levels in tumor tissue with objective response rate in patients treated with this drug. OUTLINE: This is a multicenter study. Patients receive PS-341 IV over 3-5 seconds on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients are followed every 3-6 months for up to 2 years after registration. PROJECTED ACCRUAL: A total of 22-50 patients will be accrued for this study within 12 months.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Recurrent Melanoma, Stage IV Melanoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
50 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (bortezomib)
Arm Type
Experimental
Arm Description
Patients receive PS-341 IV over 3-5 seconds on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Intervention Type
Drug
Intervention Name(s)
bortezomib
Other Intervention Name(s)
LDP 341, MLN341, VELCADE
Intervention Description
Given IV
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Proportion of patients who are progression-free
Description
Confidence intervals for the true success proportion will be calculated.
Time Frame
18 weeks
Secondary Outcome Measure Information:
Title
Objective response is defined by the Response Evaluation Criteria in Solid Tumors (RECIST) in terms of tumor/lesion size and change
Time Frame
Up to 2 years
Title
Overall survival
Description
The distribution of survival time will be estimated using the method of Kaplan-Meier.
Time Frame
Time from registration to death due to any cause, assessed up to 2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histologically or cytologically confirmed metastatic malignant melanoma Measurable disease defined as at least one lesion whose longest diameter can be accurately measured as >= 2.0 cm Absolute neutrophil count (ANC) >= 1500/uL PLT >= 100,000/uL Total bilirubin =< 2.5 x institutional upper normal limit (UNL) AST =< 2.5 x UNL Creatinine =< 1.5 x UNL or calculated creatinine clearance > 60 mL/min/1.73 m^2 for patients with creatinine levels > 1.5 x UNL using the Cockcroft-Gault formula Life expectancy of >= 3 months ECOG performance status 0 or 1 Capable of understanding the investigational nature, potential risks and benefits of the study and willing to sign the written informed consent document Exclusion Criteria: Any of the following: Any prior chemotherapy Immunotherapy =< 4 weeks prior to study entry Biologic therapy =< 4 weeks prior to study entry Radiation therapy =< 4 weeks prior to study entry Failure to fully recover from adverse effects of prior therapies regardless of interval since last treatment Other concurrent chemotherapy, immunotherapy, radiotherapy, or any other therapy or supportive care considered investigational Known brain metastases requiring active treatment; NOTE: these patients are excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events History of allergic reactions attributed to compounds of similar chemical or biologic composition to PS-341 Uncontrolled intercurrent illness including, but not limited to: Ongoing or active infection Symptomatic congestive heart failure Unstable angina pectoris, cardiac arrhythmia Psychiatric illness that would limit compliance with study requirements HIV-positive patients receiving combination anti-retroviral therapy; NOTE: patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy; these patients are excluded from the study because of possible pharmacokinetic interactions with PS-341; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated Any of the following: Pregnant women Nursing women Men or women of childbearing potential who are unwilling to employ adequate contraception (condoms, diaphragm, birth control pills, injections, subcutaneous implants, intrauterine device [IUD], abstinence, etc.) NOTE: this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown Only non-measurable disease, including lesions not clearly measurable in one dimension, small lesions (longest diameter < 20 mm), and truly non-measurable lesions, which include the following as per RECIST criteria: Bone lesions Leptomeningeal disease Ascites Pleural/pericardial effusion Inflammatory breast disease Lymphangitis cutis/pulmonis Abdominal masses that are not confirmed and followed by imaging techniques Cystic lesions
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Svetomir Markovic
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States

12. IPD Sharing Statement

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PS-341 in Treating Patients With Metastatic Malignant Melanoma

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