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

Primary Purpose

Stage IA Breast Cancer, Stage IB Breast Cancer, Stage II Breast Cancer

Status

Unknown status

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

telapristone acetate

placebo

therapeutic conventional surgery

laboratory biomarker analysis

questionnaire administration

About this trial

This is an interventional treatment trial for Stage IA Breast Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

Northwestern University

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Arm I (telapristone acetate)

Arm II (placebo)

Arm Description

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

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

Outcomes

Primary Outcome Measures

Measurable decrease in tumor growth from baseline to time of surgery

Treatment efficacy will be assessed by comparing tissue samples from the baseline biopsy and tissue samples collected from the day of surgery to measure if there is a decrease in tumor growth.

Secondary Outcome Measures

Compare changes in expression of apoptosis marker at the time of surgery

Using tissue samples, the expression of apoptosis marker will be measured in the intervention group and compared to the placebo group at the time of surgery.

Measure changes in blood estradiol and progesterone levels

Serum estradiol and progesterone levels will be measured at baseline and at the time of surgery to assess any changes.

Compare breast tissue concentrations of study drug and its metabolite (CDB4453) to plasma concentrations at the end of treatment

Breast tissue concentrations of study drug will be measured in tumor and normal tissue adjacent to the tumor at the time of surgery. Plasma concentrations of drug will also be measured for comparison to see if there is a correlation between tissue concentration of drug and the reduction in tumor growth after treatment.

Liver and renal function as well as symptom evaluation (via questionnaire) will be analyzed to assess adverse events experienced

Adverse events will be assessed throughout treatment by evaluating liver and renal function tests that will be performed at baseline, week 4, and at the post-intervention (pre-surgical) visit. Symptom measurements (using a questionnaire) will be performed at baseline, post-intervention (pre-surgical), and 1 month following surgery.

Full Information

NCT ID

NCT01800422

First Posted

February 24, 2013

Last Updated

January 16, 2020

Sponsor

Northwestern University

Collaborators

Breast Cancer Research Foundation, Repros Therapeutics Inc.

1. Study Identification

Unique Protocol Identification Number

NCT01800422

Brief Title

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

Official Title

Presurgical Phase IIB Trial of Oral CDB-4124 vs. Placebo in Women With Stage I-II Primary Breast Cancer

Study Type

Interventional

2. Study Status

Record Verification Date

January 2020

Overall Recruitment Status

Unknown status

Study Start Date

June 2013 (undefined)

Primary Completion Date

June 2021 (Anticipated)

Study Completion Date

March 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Northwestern University

Collaborators

Breast Cancer Research Foundation, Repros Therapeutics Inc.

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Stage IA Breast Cancer, Stage IB Breast Cancer, Stage II Breast Cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Arm I (telapristone acetate)

Arm Type

Experimental

Arm Description

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

Arm Title

Arm II (placebo)

Arm Type

Placebo Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

telapristone acetate

Other Intervention Name(s)

CDB-4124, Proellex, Progenta, progesterone receptor inhibitor CDB-4124

Intervention Description

Given orally

Intervention Type

Other

Intervention Name(s)

placebo

Other Intervention Name(s)

PLCB

Intervention Description

Given orally

Intervention Type

Procedure

Intervention Name(s)

therapeutic conventional surgery

Intervention Description

Undergo surgical resection

Intervention Type

Other

Intervention Name(s)

laboratory biomarker analysis

Intervention Description

Correlative studies

Intervention Type

Other

Intervention Name(s)

questionnaire administration

Intervention Description

Ancillary studies

Primary Outcome Measure Information:

Title

Measurable decrease in tumor growth from baseline to time of surgery

Description

Treatment efficacy will be assessed by comparing tissue samples from the baseline biopsy and tissue samples collected from the day of surgery to measure if there is a decrease in tumor growth.

Time Frame

Baseline to time of surgery (between 2-10 weeks, up to 10 weeks)

Secondary Outcome Measure Information:

Title

Compare changes in expression of apoptosis marker at the time of surgery

Description

Using tissue samples, the expression of apoptosis marker will be measured in the intervention group and compared to the placebo group at the time of surgery.

Time Frame

At time of surgery (between 2-10 weeks, up to 10 weeks)

Title

Measure changes in blood estradiol and progesterone levels

Description

Serum estradiol and progesterone levels will be measured at baseline and at the time of surgery to assess any changes.

Time Frame

Baseline to time of surgery (between 2-10 weeks, up to 10 weeks)

Title

Compare breast tissue concentrations of study drug and its metabolite (CDB4453) to plasma concentrations at the end of treatment

Description

Time Frame

At the time of surgery (between 2-10 weeks, up to 10 weeks)

Title

Liver and renal function as well as symptom evaluation (via questionnaire) will be analyzed to assess adverse events experienced

Description

Time Frame

At baseline and every 2 weeks while on treatment, day of surgery (between 2-10 weeks, up to 10 weeks), and 1 month following surgery

Other Pre-specified Outcome Measures:

Title

Measure protein expression of related biomarkers

Description

Measurement of protein expression in related biomarkers will be taken, from biopsy tissue, at baseline and on the day of surgery.

Time Frame

At baseline to time of surgery (between 2-10 weeks, up to 10 weeks)

Title

Perform RNA microarray analysis comparing tumors and normal tissue between patients receiving study drug and patients receiving placebo

Description

RNA microarray analysis will be conducted at baseline and on the day of surgery comparing tumors as well as normal tissue from the patients receiving treatment drug and patients receiving placebo.

Time Frame

Baseline to time of surgery (between 2-10 weeks, up to 10 weeks)

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Seema Khan, MD

Organizational Affiliation

Northwestern University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Northwestern University

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60611

Country

United States

12. IPD Sharing Statement

Learn more about this trial

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

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