Trial Outcomes & Findings for Study of Patients With Stage IV Malignant Melanoma Using PS-341 (Bortezomib, Velcade) and Interferon-alpha-2b in Malignant Melanoma (NCT NCT01462773)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

16 participants

Primary outcome timeframe

up to 25 weeks or until disease progression

Results posted on

2015-01-13

Participant Flow

Participant milestones

Participant milestones
Measure	Bortezomib & Interferon-a Bortezomib was administered intravenously weekly along with IFN-a thrice weekly.
Overall Study STARTED	16
Overall Study COMPLETED	16
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment (Enzyme Inhibitor, Interferon Therapy) n=16 Participants 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.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	12 Participants n=5 Participants
Age, Categorical >=65 years	4 Participants n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants
Region of Enrollment United States	16 patients n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Bortezomib & Interferon-a n=16 Participants Patients were treated on a 5-week cycle. Week 1 of cycle 1, patients received 5 million U/m(2) IFN-a subcutaneously thrice weekly. Weeks 2-4 of cycle 1, bortezomib was administered intravenously weely along with IFN-a thrice weekly. A break from treatment during week 5. Folllowing cycle 1, bortezomib was administered in combination iwth IFN-a. Bortezomib was administered in escalating doses to cohorts of 3 patients.
Determine Dose Limiting Toxicities (DLTs) of VELCADE When Administered in Combination With IFN-α-2b to Patients With Metastatic Malignant Melanoma. Grade 4 fatigue	3 toxicities
Determine Dose Limiting Toxicities (DLTs) of VELCADE When Administered in Combination With IFN-α-2b to Patients With Metastatic Malignant Melanoma. Grade 4 Lymphopenia	1 toxicities

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Bortezomib & Interferon-a n=16 Participants Patients were treated on a 5-week cycle. Week 1 of cycle 1, patients received 5 million U/m(2) IFN-a subcutaneously thrice weekly. Weeks 2-4 of cycle 1, bortezomib was administered intravenously weely along with IFN-a thrice weekly. A break from treatment during week 5. Folllowing cycle 1, bortezomib was administered in combination iwth IFN-a. Bortezomib was administered in escalating doses to cohorts of 3 patients.
Document Any Objective Anti-tumor Responses and Time to Tumor Progression That May Occur in Response to This Treatment Regimen. stable disease	7 patients
Document Any Objective Anti-tumor Responses and Time to Tumor Progression That May Occur in Response to This Treatment Regimen. partial response	1 patients

Adverse Events

Treatment (Enzyme Inhibitor, Interferon Therapy)

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Treatment (Enzyme Inhibitor, Interferon Therapy) n=16 participants at risk Patients were treated on a 5-week cycle. In week 1 of cycle 1, patients received 5 million U/m(2) IFN-α subcutaneously thrice weekly. During weeks 2-4 of cycle 1, bortezomib was administered intravenously weekly along with IFN-α thrice weekly. There was a treatment break during week 5. After cycle 1, bortezomib was administered in combination with IFN-α. Bortezomib was administered in escalating doses (1.0, 1.3, or 1.6 mg/m) to cohorts of 3 patients.
General disorders Fatigue	50.0% 8/16 • Number of events 8 Adverse events were determined using the NCI CTCAE (Common Terminology Criteria for Adverse Events) version 3.0 as a guideline.
Investigations Lymphopenia	6.2% 1/16 • Number of events 1 Adverse events were determined using the NCI CTCAE (Common Terminology Criteria for Adverse Events) version 3.0 as a guideline.
Gastrointestinal disorders Diarrhea	18.8% 3/16 • Number of events 3 Adverse events were determined using the NCI CTCAE (Common Terminology Criteria for Adverse Events) version 3.0 as a guideline.
Gastrointestinal disorders Vomiting	18.8% 3/16 • Number of events 3 Adverse events were determined using the NCI CTCAE (Common Terminology Criteria for Adverse Events) version 3.0 as a guideline.

Additional Information

William Carson

The Ohio State University Comprehensive Cancer Center

Phone: 614-293-6306

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place