Ignite Creation Date:
2024-05-05 @ 11:27 AM
Last Modification Date:
2024-10-26 @ 9:08 AM
Study NCT ID:
NCT00048334
Status:
COMPLETED
Last Update Posted:
2019-12-12
First Post:
2002-10-29
Brief Title:
Depsipeptide to Treat Thyroid and Other Advanced Cancers
Sponsor:
National Cancer Institute NCI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Phase I Trial of Romidepsin Given on Days One Three and Five in Patients With Thyroid and Other Advanced Cancers
Status:
COMPLETED
Status Verified Date:
2014-01-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This phase I study will evaluate the experimental drug Romidepsinin patients with advanced cancer The study will 1 determine how well patients tolerate Romidepsin 2 measure blood levels of Romidepsin during treatment 3 analyze the cellular and molecular effects of the drug and 4 determine if Romidepsin can shrink tumors Romidepsin has been shown to kill cancer cells growing in the laboratory and to shrink tumors in animals with various tumor types In preliminary studies several patients with a type of lymphoma and one patient with kidney cancer responded to treatment
Patients 18 years of age and older with advanced cancer excluding acute leukemia may be eligible for this study Candidates are screened with a medical history and physical examination x-rays and CT scans and blood and urine tests Patients with thyroid cancer may also have magnetic resonance imaging MRI This test uses a magnetic field instead of x-rays to obtain images or body organs and tissues
Participants receive three infusions of Romidepsin administered through an intravenous line over 4 hours on days 1 3 and 5 of a 21-day treatment cycle The intravenous line is a catheter plastic tube placed in a vein and may be a peripheral line inserted in a vein in the arm or a central line in which the tube is placed under the skin of the chest or neck into a major vein Patients are hospitalized for the first 6 days of the first cycle to monitor heart rate Those who tolerate the treatment well may continue as an outpatient
In addition to drug therapy participants undergo the following procedures
Blood tests Small amounts of blood are drawn frequently during the first five days of treatment to measure Romidepsin levels and to see how the body uses and excretes the drug A heparin lock an indwelling device to keep the vein open may be put in the vein to prevent the need for repeated needle sticks
Biopsies removal of a small sample of tumor tissue Tumors that are accessible may be biopsied at the start of the study and at different times during treatment Biopsies are done no more than three times per cycle and no more than nine biopsies are done within a year The samples are examined for the effects of Romidepsin on proteins that control the way cells divide and stay alive
Apheresis This procedure is done to collect white blood cells and cancer cells for research Blood is collected through a needle in an arm vein and directed into a machine that separates it into its components by centrifugation spinning The white cells are removed and the red cells are returned to the patient through the same needle or through another needle in the other arm
Scans and x-rays Imaging studies are usually done before starting treatment Some of them are repeated at every 2 cycles 6 weeks and some at the end of the patients participation in the study The tests may include chest x-rays plain x-rays of affected bones CT scans of the chest abdomen and pelvis bone scans and a MUGA scan special X-ray of the heart or echocardiogram ultrasound of the heart to test heart function before and during the study MRI or positron emission tomography PET scans may also be done to detect tumors PET scans use a small amount of a radioactive substance injected into a vein The radioactivity is detected by a special camera during scanning to detect cancer cells
Other tests include an electrocardiogram recording of the electrical activity of the heart before and after each dose of depsipeptide Eye exams are done if there are vision changes or if the doctor recommends an eye test
Patients 18 years of age and older with advanced cancer excluding acute leukemia may be eligible for this study Candidates are screened with a medical history and physical examination x-rays and CT scans and blood and urine tests Patients with thyroid cancer may also have magnetic resonance imaging MRI This test uses a magnetic field instead of x-rays to obtain images or body organs and tissues
Participants receive three infusions of Romidepsin administered through an intravenous line over 4 hours on days 1 3 and 5 of a 21-day treatment cycle The intravenous line is a catheter plastic tube placed in a vein and may be a peripheral line inserted in a vein in the arm or a central line in which the tube is placed under the skin of the chest or neck into a major vein Patients are hospitalized for the first 6 days of the first cycle to monitor heart rate Those who tolerate the treatment well may continue as an outpatient
In addition to drug therapy participants undergo the following procedures
Blood tests Small amounts of blood are drawn frequently during the first five days of treatment to measure Romidepsin levels and to see how the body uses and excretes the drug A heparin lock an indwelling device to keep the vein open may be put in the vein to prevent the need for repeated needle sticks
Biopsies removal of a small sample of tumor tissue Tumors that are accessible may be biopsied at the start of the study and at different times during treatment Biopsies are done no more than three times per cycle and no more than nine biopsies are done within a year The samples are examined for the effects of Romidepsin on proteins that control the way cells divide and stay alive
Apheresis This procedure is done to collect white blood cells and cancer cells for research Blood is collected through a needle in an arm vein and directed into a machine that separates it into its components by centrifugation spinning The white cells are removed and the red cells are returned to the patient through the same needle or through another needle in the other arm
Scans and x-rays Imaging studies are usually done before starting treatment Some of them are repeated at every 2 cycles 6 weeks and some at the end of the patients participation in the study The tests may include chest x-rays plain x-rays of affected bones CT scans of the chest abdomen and pelvis bone scans and a MUGA scan special X-ray of the heart or echocardiogram ultrasound of the heart to test heart function before and during the study MRI or positron emission tomography PET scans may also be done to detect tumors PET scans use a small amount of a radioactive substance injected into a vein The radioactivity is detected by a special camera during scanning to detect cancer cells
Other tests include an electrocardiogram recording of the electrical activity of the heart before and after each dose of depsipeptide Eye exams are done if there are vision changes or if the doctor recommends an eye test
Detailed Description:
BACKGROUND
Romidepsin NSC 630176 FR901228 FK228 formerly referred to as depsipeptide is a histone deacetylase inhibitor with potent cytotoxic activity against human tumor cell lines and in vivo efficacy against both human tumor xenografts and murine tumors 1-3
Laboratory studies suggest that longer exposure to non-toxic doses of romidepsin can enhance its molecular effects to a greater degree than short toxic doses that rapidly cause cell death
NIS is responsible for enabling uptake of RAI in thyroid cancer with decreased levels in tumors resistant or refractory to RAI therapy
Our group has demonstrated that NIS expression is upregulated by romidepsin resulting in increased sensitivity to RAI
OBJECTIVES
To determine the MTD of romidepsin when administered on days 1 3 and 5
To examine the effect of a multi-day regimen of romidepsin on surrogate markers and the expression of molecular targets
To determine whether thyroid cancers that do not have detectable uptake of RAI will have detectable uptake after treatment
ELIGIBILITY
Age 18 and over
Evaluable disease
Performance status ECOG 0-2
Excluding patients that are pregnant HIV positive have CNS metastasis or acute leukemia
Left ventricular ejection fraction within normal limits Additional cardiac criteria are noted in protocol
DESIGN
Phase I
Romidepsin administered as a 4-hour intravenous infusion on days 1 3 and 5
Dose escalation
Enrollment of additional cohort of 10 patients with thyroid cancer at MTD
Romidepsin NSC 630176 FR901228 FK228 formerly referred to as depsipeptide is a histone deacetylase inhibitor with potent cytotoxic activity against human tumor cell lines and in vivo efficacy against both human tumor xenografts and murine tumors 1-3
Laboratory studies suggest that longer exposure to non-toxic doses of romidepsin can enhance its molecular effects to a greater degree than short toxic doses that rapidly cause cell death
NIS is responsible for enabling uptake of RAI in thyroid cancer with decreased levels in tumors resistant or refractory to RAI therapy
Our group has demonstrated that NIS expression is upregulated by romidepsin resulting in increased sensitivity to RAI
OBJECTIVES
To determine the MTD of romidepsin when administered on days 1 3 and 5
To examine the effect of a multi-day regimen of romidepsin on surrogate markers and the expression of molecular targets
To determine whether thyroid cancers that do not have detectable uptake of RAI will have detectable uptake after treatment
ELIGIBILITY
Age 18 and over
Evaluable disease
Performance status ECOG 0-2
Excluding patients that are pregnant HIV positive have CNS metastasis or acute leukemia
Left ventricular ejection fraction within normal limits Additional cardiac criteria are noted in protocol
DESIGN
Phase I
Romidepsin administered as a 4-hour intravenous infusion on days 1 3 and 5
Dose escalation
Enrollment of additional cohort of 10 patients with thyroid cancer at MTD
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 03-C-0030 | None | None | None |