Phase I Trial of Sequential Azacitidine and Valproic Acid Plus Carboplatin in the Treatment of Patients With Platinum Resistant Epithelial Ovarian Cancer
The Study Drugs:
Researchers want to see if the combination of azacitidine, carboplatin, and valproic may
work better together to control advanced cancer.
- Azacitidine is designed to activate ("turn on") certain genes in cancer cells whose job
is to fight tumors, which may also make azacitidine work better with other anti-tumor
- Carboplatin is designed to block the growth of cancer cells by stopping cell division,
which may cause the cells to die.
- Valproic acid is an anti-seizure medication that may also have cancer-fighting
abilities. This drug may be able to activate tumor-fighting genes, causing cancer cells
Phase 1 (Dose Escalation) and Phase 2 (Treatment):
Participants will be enrolled on Phase 1 of the study in groups of 3. Each group will
receive a different combination of the study drugs. If the first group of 3 tolerates the
study drug combination well, the next group of 3 will be enrolled, and their dose(s) of
carboplatin and/or valproic acid will be higher than the last group. Each new group will
get a higher dose of carboplatin and/or valproic acid. If 1 of the 3 participants has a
serious side effect at a certain dose level, 3 more participants may be added at that dose
level to check the safety of the combination. If no more participants at that dose level
have serious side effects, the next dose level will be tested. However, if a second
participant has a serious side effect, then the dose level before that one will be
considered the "maximum tolerated dose" (MTD). Once the MTD is found, participants will be
enrolled on Phase 2 of the study.
Participants enrolled on Phase 2 were to be given the MTD level of the study drug
combination; however, study did not progress to Phase 2.
Participants on both phases were to have the same treatment schedule and study tests
performed. The only difference between Phase 1 and Phase 2 was to be the dose level of the
study drug combination being given.
If eligible, participants received the study treatment on a 28-day treatment cycle.
On Day 1 of each cycle, they receive an injection of azacitidine just under the skin or by
vein over 30 minutes once a day for 5 days in a row.
On Day 3 and Day 10 of each cycle, they receive carboplatin by vein over 60 minutes.
On Days 5-11 of each cycle, they take valproic acid by mouth once a day with or without
On Day 12 of each cycle, they may receive an injection of NeulastaTM (pegfilgrastim) just
under the skin, depending on whether the study doctor thinks it is needed to help boost your
white blood cell count.
On Days 13-28 of each cycle, they have a "rest period" from the study drugs before beginning
a new 28-day cycle of treatment.
At certain time points, they have the following tests/procedure performed during study
On Day 5 and Day 11 of Cycles 1-3, about 1 tablespoon of blood drawn before treatment for
molecular marker studies. These tests will be performed to look for a link between genetic
characteristics and response to the study drug treatment.
Within the last 72 hours (3 days) of each cycle, blood drawn (about 1 tablespoon) and urine
collected for routine tests. After the start of each cycle, blood drawn (about 1 tablespoon)
once weekly for routine tests.
Within 7 days before starting each new cycle, evaluation to see if you may be experiencing
any side effects.
After the end of every 2 cycles (about every 8 weeks), an x-ray and either a CT scan or an
MRI scan to re-evaluate the cancer.
Length of Study:
Participants will continue to receive treatment on this study, as long as the disease does
not get worse and you do not experience any intolerable side effects.
Once treatment has ended for any reason, participants will come back for an end-of-treatment
visit to have the following tests/procedures performed:
- You will have a complete physical exam.
- You will have urine collected and blood drawn (about 1 tablespoon) for routine tests.
- You may have a CT scan or an MRI scan to remeasure and re-evaluate the cancer.
Up to 65 patients were eligible to take part in this study. All were to be enrolled at M. D.
Anderson. Study halted after Phase 1 without progressing to second phase.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Assessment of tumor response by palpation, plain x-ray, MRI, or CT scan to be obtained after the first cycle and the every 2 cycles after that (8 weeks).
Gerald Falchook, MD
M.D. Anderson Cancer Center
United States: Institutional Review Board
|UT MD Anderson Cancer Center||Houston, Texas 77030|