Phase I Study of Gimatecan in Patients With Myelodysplastic Syndromes
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I Study of Gimatecan in Patients With Myelodysplastic Syndromes|
- Maximum Tolerated Dose (MTD) of Gimatecan [ Time Frame: Evaulate with each 28 Day Cycle ]For purposes of estimating the MTD, 5 dose levels of Gimatecan initially considered. These dose levels are 3 mg, 5 mg, 7.5 mg, 8.75 mg, and 10 mg orally per cycle. Dose escalation based on toxicities observed through the first cycle.
- Efficacy in terms of complete remission , complete remission w/ incomplete platelet or neutrophil recovery (CRp and CRn, respectively), partial remission , and hematologic improvement. [ Time Frame: Up to 12 Months on Study ]Response criteria according to the International Working Group (Blood 2006; 108: 419-425). Responders are patients who obtain a Complete Response (CR), CRi, Partial Response (PR), with or without cytogenetic response, hematologic improvements, and morphologic leukemia-free state.
|Study Start Date:||August 2007|
|Study Completion Date:||May 2014|
|Primary Completion Date:||May 2014 (Final data collection date for primary outcome measure)|
Gimatecan Starting dose: 0.6 mg capsules administered orally once daily.
Starting dose: 0.6 mg capsules administered orally once daily.
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The Study Drug:
Gimatecan is designed to block the function of an important protein (topoisomerase I) in cancer cells that helps repair damage to DNA (the genetic material of cells). When this protein is blocked, cancer cells may die.
Before you can start receiving the study drug, you will have what are called "screening tests." These tests will help the doctor decide if you are eligible to take part in this study.
- You will have a physical exam.
- Your complete medical history will be recorded.
- Your vital signs (blood pressure, pulse, breathing rate, and temperature), height, and weight will be measured.
- You will be asked how well you are able to perform the normal activities of daily living (a performance status evaluation).
- You will be asked about any medications you may be taking.
- Blood (about 1 tablespoon) will be drawn for routine tests.
- Women who are able to have children must have a negative blood (about 2 teaspoons) or urine pregnancy test.
- You will have a bone marrow aspirate performed. To collect a bone marrow aspirate, an area of the hip is numbed with anesthetic, and a small amount of bone marrow is withdrawn through a large needle.
- If your doctor thinks it is necessary, you will have a bone marrow biopsy when you have the bone marrow aspirate done. To collect a bone marrow biopsy, an area of the hip is numbed with anesthetic, and a small amount of bone marrow and bone is withdrawn through a large needle.
- You will complete a questionnaire to see how the disease may be affecting your ability to do your daily activities. The questionnaire will take about 15 minutes to complete.
Study Drug Dose Level:
If you are found to be eligible to take part in this study, the amount of study drug you receive will be based on when you join the study. Three (3) to 6 participants will be enrolled in this study and given a certain dose. If they do not experience intolerable side effects, the next 3-6 participants enrolled will receive a higher dose. This process will continue until researchers find the highest dose of the drug that can be given without causing serious or intolerable side effects. The study doctor will tell you what dose you will be receiving and how this compares to the doses other participants have received.
Study Drug Administration:
You will take gimatecan on Days 1-5. On Days 6-28, you will take no study drug. Each 28-day period is called a study "cycle." If your doctor thinks it is necessary, your study cycles may be shortened so that you will receive the study drug more often.
You will take the medication on an empty stomach, swallowing the capsules whole. You should not eat for 1 hour after taking the medication. If you take other medications while you are on this study, they must be taken 4 hours before or after you take gimatecan.
Blood (about 2 tablespoons each time) will be drawn for routine tests every 1-4 weeks for the length of this study. Most of these blood tests will be done once a week, but some will only be done once every 4 weeks.
You will have a physical exam every 4 weeks for the first 3 months, then every 3 months.
At the end of Cycle 1, and then every 9-12 weeks after that, you will have a bone marrow aspirate and/or biopsy. Bone marrow biopsies and aspirates may be collected more often if your study doctor thinks it is necessary.
Once per week for the first 3 cycles, you will complete a symptom questionnaire. This will be done either at a study visit, or you will be called by a member of study staff. The questionnaire will take about 15 minutes to complete.
Length of Study:
You can remain on this study for up to 12 months. If, after this time, it is considered that gimatecan is helping you, the study doctor will discuss the possibility of continuing the study drug therapy outside of this study. You may be taken off this study early if the disease gets worse or intolerable side effects occur.
Once you are off this study, you will have an end-of-study visit, and the following tests will be performed.
- You will have a physical exam.
- You will be asked about any side effects you may be experiencing.
- Blood (about 4 teaspoons) will be drawn for routine tests.
- You will repeat the symptom questionnaire.
This is an investigational study. Gimatecan is not FDA approved or commercially available. It has been authorized for use in research only. Up to 30 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: NCT00493571
|United States, Texas|
|The University of Texas M.D. Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Jorge E. Cortes, MD||M.D. Anderson Cancer Center|