Parallel Phase I/II Trial of Decitabine and Peg-Interferon in Melanoma: Phase I Portion
The goal of the first phase of this clinical research study is to find the highest tolerable dose of decitabine and peginterferon alfa-2b that can be given in combination to patients with melanoma. The safety of this drug combination will also be studied.
The goals of the second phase are to learn if decitabine and peginterferon alfa-2b combined can help to control melanoma, and to find out which doses are more effective and/or better tolerated.
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Parallel Phase I/II Study of Low Dose Decitabine (5-Aza-Deoxycytidine) With Peginterferon Alfa-2b in Advanced Melanoma|
- Phase I: Dose-limiting toxicity (DLT) [ Time Frame: 4 weeks ]
Dose limiting toxicity defined as any treatment related toxicity that meets one or more of the following criteria:
Any grade 3 or 4 non-hematologic toxicity regardless of duration, except:
- Grade 3 nausea or vomiting occurring without maximal antiemetic therapy.
Grade 3 diarrhea that occurs following without adequate loperamide therapy.
- Grade 4 thrombocytopenia.
- Grade 4 neutropenia lasting > 2 weeks or associated with infection.
- Any toxicity that results in a treatment delay of > 4weeks.
- Phase II: Patient Response [ Time Frame: 12 weeks ]Success defined as either a complete response (CR), a partial response (PR), or stable disease (SD). Target combined endpoint of CR+PR+SD in this trial is 30%. Evaluation of response follows the Response Evaluation Criteria in Solid Tumors (RECIST) Guidelines.
|Study Start Date:||September 2008|
|Study Completion Date:||May 2015|
|Primary Completion Date:||May 2015 (Final data collection date for primary outcome measure)|
Experimental: Decitabine + Peginterferon Alfa-2b
Decitabine starting dose of 10mg/m^2 given daily via intravenous infusion on days 1-5 of 28 day cycle. Peginterferon Alfa-2b starting dose of 3 µg/kg injection under the skin once a week on days 1, 8, 15, and 21 of 28 day cycle.
Starting dose of 10mg/m^2 given daily via intravenous infusion on days 1-5 of 28 day cycle.
Other Names:Drug: Pegylated Interferon Alpha-2b
Starting dose of 3 µg/kg injection under the skin once a week on days 1, 8, 15, and 21 of 28 day cycle.
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The Study Drugs:
Decitabine is designed to damage the DNA of cells, which may cause cancer cells to die.
Peginterferon alfa-2b is designed to strengthen the immune system, which may decrease tumor growth.
If you are found to be eligible to take part in this study, you will be assigned to a study group based on when you joined this study. Up to 6 groups of 3-6 participants will be enrolled in the Phase I portion of the study, and up to 44 participants will be enrolled in Phase II.
If you are enrolled in the Phase I portion, the dose of decitabine and peginterferon alfa-2b you receive will depend on when you joined this study. The first group of participants will receive the lowest dose level of the study drug combination. Each new group will receive a higher dose level than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of the study drug combination is found.
If you are enrolled in the Phase II portion, the dose of decitabine and peginterferon alfa-2b you receive will depend on when you joined this study, as well as the research data from the Phase I portion. You will be randomly assigned (as in the roll of dice) to receive one of the dose levels (which may be from 1 to 6 dose levels, depending on the available data from the Phase I portion) that have been found in the Phase I portion to have the least side effects and to be possibly the most effective. This means you will have an equal chance of being assigned to any of the dose levels that are being used at that time. As the study goes on, if the research data suggests that one dose level may be better tolerated than the others, new participants enrolling into the Phase II portion would be more likely to be assigned to that possibly better dose level.
No matter which phase you are enrolled in, your dose of the study drugs may be lowered if you do not tolerate the study drug combination well.
Study Drug Administration:
A "cycle" on this study is 28 days. Decitabine will be given by vein, over 1 hour, on Days 1-5 of each cycle. Peginterferon alfa-2b will be given by injection under the skin, once a week (on Days 1, 8, 15, and 21). You will be giving peginterferon alfa-2b to yourself under nursing supervision on the days you are receiving decitabine.
On Day 6 of each cycle, you will either receive Neulasta (pegfilgrastim) or Neupogen (filgrastim). Pegfilgrastim or filgrastim will be injected under your skin. If you receive pegfilgrastim, it will be injected only on Day 6 of each cycle. If you receive filgrastim, it will be injected 1 time a day for as many days as the doctor decides is needed to raise your white blood cell count.
On Day 1 of each cycle, the following procedures will be performed:
- You will have a physical exam, including measurement of your vital signs and weight.
- You will be asked about any medications or treatments you may be currently receiving and any side effects you may have experienced.
- You will have a performance status evaluation.
- Blood (about 1 teaspoon) will be drawn for routine tests.
These same tests listed above will be repeated at additional visits with the research nurse during Week 3 of Cycles 1 and 2. If you do not experience severe side effects during Cycles 1 and 2, these extra Week 3 visits with the research nurse will no longer be necessary in later cycles. They may, however, be started again if needed.
At the end of of Cycle 3, and every odd cycle after that (Cycles 5, 7, 9, and so on), you will have a scan performed (such as CT or MRI) to check the status of the disease.
Length of Study Participation:
You may remain on study for as long as you are benefitting. If the disease gets worse or intolerable side effects occur, you will be taken off study early.
Once you go off study for any reason, you will have an end-of-study visit with the same procedures performed as the Day 1 study visits. You may also have a scan performed (such as CT or MRI) to check the status of the disease if you have not had one performed in the last 4 weeks.
Every 3 months for about 2 years, researchers will call you to see how you are doing.
This is an investigational study. Decitabine is FDA approved and commercially available for the treatment of myelodysplastic syndrome (MDS). Peginterferon alfa-2b is FDA approved and commercially available for the treatment of hepatitis C. Their use together in this study in the treatment of melanoma is considered experimental. At this time, the combination is being used in research only.
Up to 80 patients will take part in this study. All will be enrolled at M. D. Anderson.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00791271
|United States, Texas|
|University of Texas MD Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Wen-Jen Hwu, MD, PhD||M.D. Anderson Cancer Center|