Oral CDB-4124 vs. Placebo in Stage I-II Primary Breast Cancer
| Status: | Active, not recruiting |
|---|---|
| Conditions: | Breast Cancer, Cancer, Cancer, Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 4/17/2018 |
| Start Date: | June 2013 |
| End Date: | March 2020 |
Presurgical Phase IIB Trial of Oral CDB-4124 vs. Placebo in Women With Stage I-II Primary Breast Cancer
The purpose of this study is to determine whether or not the medication that blocks the
effects of the hormone progesterone (CDB-4124 or Proellex) will decrease the growth rate of
breast cancer cells as compared to a placebo. CDB-4124 (also called Proellex) is a medication
that works against the hormone, progesterone. The researchers in this study would like to
compare changes in breast cancer cells of women who have taken CDB-4124 prior to surgery to
those from women who have taken a placebo pill prior to surgery.
effects of the hormone progesterone (CDB-4124 or Proellex) will decrease the growth rate of
breast cancer cells as compared to a placebo. CDB-4124 (also called Proellex) is a medication
that works against the hormone, progesterone. The researchers in this study would like to
compare changes in breast cancer cells of women who have taken CDB-4124 prior to surgery to
those from women who have taken a placebo pill prior to surgery.
PRIMARY OBJECTIVES:
I. To test the hypothesis that treatment with the selective progesterone receptor modulator
(SPRM) CDB-4124 (telapristone acetate) will have an anti-tumor effect in women with
early-stage breast cancer, defined as a significant decrease in tumor proliferation (Ki67
labeling index).
SECONDARY OBJECTIVES:
I. Measure changes in apoptosis using IHC (cleaved caspase 3 or TUNEL). II. Measure changes
in blood estradiol and progesterone levels. III. Compare the breast tissue concentrations of
CDB-4124 and its metabolite (CDB4453) to plasma concentrations at the end of therapy.
IV. Assess adverse events.
TERTIARY OBJECTIVES:
I. Measure protein expression of related targets (including estrogen receptor alpha (ERA),
estrogen receptor beta (ERB), progesterone receptor isoforms progesterone receptor alpha
[PRA], progesterone receptor beta [PRB], tumor necrosis factor receptor superfamily, member
11a, NFKB activator [RANK], tumor necrosis factor (ligand) superfamily, member 11 [RANKL],
and either cyclin-dependent kinase 2 [cdk2] or cyclin-dependent kinase 4 [cdk4],) using IHC
at baseline and after treatment.
II. Perform ribonucleic acid (RNA) microarray analysis comparing tumors and normal tissue
from the intervention and control groups.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive telapristone acetate orally (PO) once daily (QD) for 2-10 weeks and
then undergo surgical resection.
ARM II: Patients receive placebo orally once daily for 2-10 weeks and then undergo surgical
resection.
After completion of study treatment, patients are followed up for 1 month.
I. To test the hypothesis that treatment with the selective progesterone receptor modulator
(SPRM) CDB-4124 (telapristone acetate) will have an anti-tumor effect in women with
early-stage breast cancer, defined as a significant decrease in tumor proliferation (Ki67
labeling index).
SECONDARY OBJECTIVES:
I. Measure changes in apoptosis using IHC (cleaved caspase 3 or TUNEL). II. Measure changes
in blood estradiol and progesterone levels. III. Compare the breast tissue concentrations of
CDB-4124 and its metabolite (CDB4453) to plasma concentrations at the end of therapy.
IV. Assess adverse events.
TERTIARY OBJECTIVES:
I. Measure protein expression of related targets (including estrogen receptor alpha (ERA),
estrogen receptor beta (ERB), progesterone receptor isoforms progesterone receptor alpha
[PRA], progesterone receptor beta [PRB], tumor necrosis factor receptor superfamily, member
11a, NFKB activator [RANK], tumor necrosis factor (ligand) superfamily, member 11 [RANKL],
and either cyclin-dependent kinase 2 [cdk2] or cyclin-dependent kinase 4 [cdk4],) using IHC
at baseline and after treatment.
II. Perform ribonucleic acid (RNA) microarray analysis comparing tumors and normal tissue
from the intervention and control groups.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive telapristone acetate orally (PO) once daily (QD) for 2-10 weeks and
then undergo surgical resection.
ARM II: Patients receive placebo orally once daily for 2-10 weeks and then undergo surgical
resection.
After completion of study treatment, patients are followed up for 1 month.
Inclusion Criteria:
- Subjects must be females with a histological diagnosis of invasive breast cancer
clinical stage T1-2, N01 and be candidates for primary resection of this cancer; note:
subjects with bilateral cancer are eligible
- Primary tumor stage T1-2 at the time of initial diagnosis and ipsilateral nodes
must be N0-1 by clinical evaluation. Staging is routinely based on the NCCN
Clinical Practice Guidelines and TNM Nomenclature for Breast Cancer from AJCC
Cancer Staging Manual. All breast cancer patients routinely undergo axillary
ultrasound to evaluate nodal involvement.
- Subjects must have greater than 0.5 cm of IBC on core (5 cores).
- Subjects must be age > or = 18 years.
- Subjects must exhibit an ECOG performance status of 0 or 1.
- Subjects must be able and willing to schedule surgical resection of their tumor 2 or
more weeks following the start of the study agent.
- Subjects must have adequate hepatic and renal function, within 6 weeks prior to
registration. The liver function tests include total bilirubin (<1.5xULN; Gilbert"s
allowed 3x ULN), ALT/ AST (<2.5xULN) and alkaline phosphatase(<2.5xULN); the standard
renal function tests include blood urea nitrogen (BUN), and creatinine and must be <
2XULN.
- Subjects of child-bearing potential must agree to use adequate contraception (barrier
method of birth control; abstinence) prior to study entry, for the duration of study
participation, and for 90 days following completion of therapy.
- A female of child-bearing potential is any woman (regardless of sexual
orientation, having undergone a tubal ligation, or remaining celibate by choice)
who meets the following criteria:
- Has not undergone a hysterectomy or bilateral oophorectomy; OR
- Has not been naturally postmenopausal for at least 12 consecutive months
(i.e., has had menses at any time in the preceding 12 consecutive months).
- Subjects of child bearing potential must have a negative urine pregnancy test
within 5 days prior to first dose of the study drug.
- Subjects must have the ability to understand and the willingness to sign a written
informed consent. Informed consent must be obtained prior to registration on the study
Exclusion Criteria
- Subjects must not have a breast cancer diagnosis of ductal carcinoma in situ only
(DCIS)
- Subjects must not have received any other breast cancer-specific therapy prior to
registration
- Subjects must not have received any oral contraceptive or postmenopausal hormones
within one month prior to their diagnostic biopsy AND must agree not to use exogenous
sex hormones while on the study
- Subjects must not have a history of any significant renal or hepatic disease requiring
ongoing medical therapy or clinical intervention
- Subjects must not have a history of thromboembolic disorder or cerebral vascular
disease
- Subjects must not have a body mass index (BMI) > 39
- Subjects must not be pregnant or nursing
- Subjects must not be receiving any other investigational agents
- Subjects must not have allergies to any compounds similar to CDB-4124
- While participating, subjects must agree not to use soy supplements, over the counter
estrogen supplements like Estroven, Chinese herbs, or other over-the-counter (OTC)
herbal products
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