Oral CDB-4124 vs. Placebo in Stage I-II Primary Breast Cancer

NCT ID: NCT01800422

Last Updated: 2020-01-18

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-06-30
• Study Completion Date: 2022-03-31

Brief Summary

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.

Detailed Description

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.

Conditions

Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Arm I (telapristone acetate)

Patients receive telapristone acetate orally once daily for 2-10 weeks and then undergo surgical resection.

Group Type: EXPERIMENTAL

telapristone acetate

Intervention Type: DRUG

Given orally

therapeutic conventional surgery

Intervention Type: PROCEDURE

Undergo surgical resection

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

questionnaire administration

Intervention Type: OTHER

Ancillary studies

Arm II (placebo)

Patients receive placebo orally once daily for 2-10 weeks and then undergo surgical resection.

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: OTHER

Given orally

therapeutic conventional surgery

Intervention Type: PROCEDURE

Undergo surgical resection

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

questionnaire administration

Intervention Type: OTHER

Ancillary studies

Interventions

telapristone acetate

Given orally

Intervention Type: DRUG

placebo

Given orally

Intervention Type: OTHER

therapeutic conventional surgery

Undergo surgical resection

Intervention Type: PROCEDURE

laboratory biomarker analysis

Correlative studies

Intervention Type: OTHER

questionnaire administration

Ancillary studies

Intervention Type: OTHER

Other Intervention Names

CDB-4124; Proellex; Progenta; progesterone receptor inhibitor CDB-4124; PLCB

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Northwestern University

OTHER

Sponsor Role: lead

Breast Cancer Research Foundation

OTHER

Sponsor Role: collaborator

Repros Therapeutics Inc.

INDUSTRY

Sponsor Role: collaborator

Responsible Party

Seema Khan

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Seema Khan, MD

Role: PRINCIPAL_INVESTIGATOR

Northwestern University

Locations

Northwestern University

Chicago, Illinois, United States

Countries

United States

Other Identifiers

NCI-2012-03189

Identifier Type: REGISTRY

Identifier Source: secondary_id

STU00074599

Identifier Type: OTHER

Identifier Source: secondary_id

NU 12B09

Identifier Type: -

Identifier Source: org_study_id