A Phase I With Dose Expansion to Determine the Maximum Tolerated Dose of Liposomal Doxorubicin in Combination With Seliciclib for the Treatment of Patients With Metastatic Triple Negative Breast Cancer
18 Years
N/A
Both
Breast Cancer
Trial Information
A Phase I With Dose Expansion to Determine the Maximum Tolerated Dose of Liposomal Doxorubicin in Combination With Seliciclib for the Treatment of Patients With Metastatic Triple Negative Breast Cancer
The Study Drugs:
Seliciclib is designed to stop cancer cells from dividing, which may cause them to die.
Doxorubicin is a chemotherapy drug that is designed to stop the growth of cancer cells,
which may cause the cells to die. Liposomal doxorubicin is a redesigned version of
doxorubicin. The drug, doxorubicin, is enclosed in a fat bubble called a liposome. This is
designed to allow the drug to get into the tumor tissue better and to stay in the body for a
longer time.
Study Groups:
If you are found to be eligible to take part in this study, you will be assigned to a dose
level of seliciclib based on when you joined this study. Up to 6 dose levels of seliciclib
will be tested. At least 2 participants will be enrolled at each dose level. The first
group of participants will receive the lowest dose level. Each new group will receive a
higher dose than the group before it, if no intolerable side effects were seen. This will
continue until the highest tolerable dose of seliciclib is found.
All participants will receive the same dose level of liposomal doxorubicin.
Drug Administration:
You will take seliciclib by mouth with a cup (8 ounces) of water twice a day on Days 1-3 of
each 28-day study cycle. The 2 doses should be taken 12 hours apart. Seliciclib should be
taken 1 hour before or 2 hours after a meal. If you miss a dose, it can be taken up to 2
hours after the scheduled time. If it has been more than 2 hours, the missed dose should not
be taken. You should resume taking the study drug at the next normally scheduled time.
You will receive liposomal doxorubicin by vein over 2-3 hours on Day 4 of each cycle.
On Days 5-28 you will not receive any study drugs.
Study Visits:
At all study visits, you will be asked about any side effects you may be having and about
any other drugs you may be taking.
On Day 1 of every cycle:
- You will have a physical exam, including measurement of your weight and vital signs.
- Your performance status will be recorded.
- Blood (about 1-2 teaspoons) and urine will be collected for routine tests.
During Week 2 of Cycle 1:
-Blood (about 1-2 teaspoons) will be drawn for routine tests.
You will have an ECHO or MUGA scan at least every 4 cycles to check your heart function.
After every even-numbered cycles (Cycles 2, 4, 6 and so on), you will have either a CT or
MRI scan to check the status of the disease.
Length of Study:
You may continue taking the study drugs for as long as the doctor thinks it is in your best
interest. You will no longer be able to take the study drug if the disease gets worse, if
intolerable side effects occur, or if you are unable to follow study directions.
Your participation on the study will be over once you have completed the end-of-study visit.
End-of-Study Visit:
About 4-6 weeks after you have stopped receiving the study drugs, you will have an
end-of-study visit. The following tests and procedures will be performed:
- You will have a physical exam, including measurement of your weight and vital signs.
- Your performance status will be recorded.
- Blood (about 1-2 teaspoons) and urine will be collected for routine tests.
- You will be asked about any symptoms you may be having and drugs you may be taking.
This is an investigational study. Seliciclib is not FDA-approved or commercially available.
It is currently being used for research purposes only.
Liposomal doxorubicin is FDA-approved and commercially available for metastatic breast
cancer. The use of these drugs together is investigational.
Up to 40 patients will take part in this study. All will be enrolled at M. D. Anderson.
Inclusion Criteria:
1. Both male and female patients with invasive cancer that is confirmed ER/PR/HER2
negative carcinoma of the breast with locally advanced or stage IV disease that is
not amenable to curative therapy. For purposes of this study, triple negative disease
will be tumors that have ER/PR <10% and HER2 (ratio <2.0).
2. Patients must have an ECOG performance status of 0, 1 or 2
3. Age >/= 18 years
4. Women must not be pregnant or lactating because of the teratogenic potential of these
drugs. All females of childbearing potential (i.e. A female not free from menses > 1
year or not surgically sterilized) must have a blood test or urine study within 2
weeks prior to start of therapy to rule out pregnancy.
5. Women of childbearing potential (i.e. A female not free from menses > 1 year or not
surgically sterilized) and are strongly advised to use an accepted and effective
non-hormonal method of contraception.
6. Must have at least one site of objective measurable or evaluable disease. Baseline
measurements and evaluations must be obtained within 4 weeks of start of therapy.
7. Patients must be disease free of prior malignancy for >/= 5 years with the exception
of curatively treated squamous cell carcinomas of the skin or carcinoma in situ of
the cervix or breast.
8. Patients must have no serious medical illness, other that treated by this study,
which would limit survival to less than 1 month or psychiatric illness which would
limit informed consent.
9. Patients must not have peripheral neuropathy > grade 2.
10. Required Cardiac Parameters: Patients must not have had a history of New York Heart
Association class 3 or 4 heart failure, or history of myocardial infarction, unstable
angina or CVA within 6 months of protocol registration. LVEF > 50% by MUGA or ECHO.
11. Patients must not have history of PR prolongation or AV block
12. Required laboratory parameters: Patients must have serum creatinine < 1.5 mg/dl.
13. Patients must have adequate hematologic functions: granulocytes > 1500/mm^3 and
platelets > 100,000/mm^3
14. Patients must have adequate hepatocellular function: SGOT (AST) and SGPT (ALT) < 1.5
x upper limit of normal (unless liver is involved by tumor, in which case SGOT (AST)
and SGPT (ALT) can be < 2.0 x upper limit of normal)
15. Patients must have no history of prior therapy with seliciclib.
16. Patients must not have received a cumulative dose of doxorubicin of greater than 360
mg/m^2 or epirubicin of greater than 640 mg/m^2. Patients who have received >240
mg/m^2 of doxorubicin or >400 mg/m^2 of epirubicin should be advised to undergo
evaluation of left ventricular ejection fraction (LVEF) with echocardiogram (ECHO) or
gated heart scan (MUGA) prior to initiating therapy.
17. Concurrent use of hormonal therapy is not permitted. Concurrent radiation therapy is
not permitted.
18. Patients must not have had prior organ allograft or require immunosuppressive
therapy.
19. Patients must have completed and recovered from the effects of prior chemotherapy
(
20. Patients must have received at least one prior chemotherapy regimen for metastatic
disease. Progression within 6 months of adjuvant chemotherapy will be considered
equivalent to one prior chemotherapy for metastatic disease.
Exclusion Criteria:
1) None.
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Number of Participants with a Dose Limiting Toxicity(DLT)
Outcome Description:
Dose-limiting toxicity (DLT) defined as NCI Common Toxicity Criteria (version 4.0): Grade 3 or 4 thrombocytopenia lasting > 2 weeks; Grade 3 or 4 neutropenia lasting >2 weeks; Febrile neutropenia; Grade 3 or 4 non-hematologic toxicity that lasts > 72 hours despite appropriate medical management (excluding grade 3 fatigue); or Delay in administration of cycle 2 of therapy for >2 weeks due to myelosuppression. DLT must be considered treatment related and occur during cycle 1 of therapy.
Outcome Time Frame:
Cycle 1 of therapy (28 days)
Safety Issue:
Yes
Principal Investigator
Stacy Moulder, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
UT MD Anderson Cancer Center
Authority:
United States: Food and Drug Administration
Study ID:
2011-0013
NCT ID:
NCT01333423
Start Date:
September 2012
Completion Date:
Related Keywords:
- Breast Cancer
- Breast Cancer
- Metastatic Triple Negative
- ER/PR/HER2 negative
- Locally advanced
- Stage IV
- Metastatic
- Seliciclib
- Liposomal Doxorubicin
- Doxil
- Doxorubicin Hydrochloride (Liposomal)
- Breast Neoplasms
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