PK Cohort for Estrogen Receptor Positive Breast Cancer

Phase-Based Progress Estimates
1
Effectiveness
2
Safety
Estrogen Receptor Positive Breast Cancer+3 Moregoserelin - Drug
Eligibility
18+
Female
What conditions do you have?
Select

Study Summary

This open-label research study is studying (Z)-endoxifen as a possible treatment for pre-menopausal (still having periods) women with ER+/HER2- breast cancer. This study includes a pharmacokinetic part (PK, how the drug works in your body) and a treatment part. The primary purpose of the study is to see how (Z)-endoxifen works on tumor cell growth by taking a biopsy after 4 weeks of treatment to measure Ki-67. Ki-67 is a cancer marker that indicates how well the treatments work to slow cancer cell growth. Overall, this study will help determine if (Z)-endoxifen can effectively treat premenopausal women with ER+/HER2- breast cancer without the need for monthly injections of goserelin which is a medication given to block the ovaries from making estrogen (also called ovarian suppression). Studies have shown harmful long-term effects of ovarian suppression in premenopausal women. The PK part of the study will be enrolled first, enrolling about 6 study participants who will all receive oral once daily (Z)-endoxifen treatment. This part of the study will help select the dose of (Z)-endoxifen to use in the treatment part by measuring the levels of (Z)-endoxifen in the blood stream and determine how long it takes for the body to remove it. About 160 study participants will be enrolled in the treatment part. The treatment part will help to determine how oral once daily (Z)-endoxifen, when taken by itself, compares to oral once daily exemestane (a medication that decreases the amount of estrogen in the body, also known as an aromatase inhibitor) and monthly injections of goserelin. Exemestane and goserelin taken together is a standard treatment regimen for premenopausal patients with ER+/HER2- breast cancer. Study participants are randomly assigned to treatment with an equal (50/50) chance to be assigned to (Z)-endoxifen or standard treatment. Study participation is up to 24 weeks of treatment followed by surgery.

Eligible Conditions
  • Estrogen Receptor Positive Breast Cancer
  • Breast Cancer
  • HER2-negative Breast Cancer

Treatment Effectiveness

Effectiveness Progress

1 of 3

Study Objectives

2 Primary · 23 Secondary · Reporting Duration: Baseline Assessment up to Cycle 3 (each cycle is 28 days) or up to 12 weeks

Week 4
Both Cohorts - Percentage of subjects whose serum thymidine kinase 1 (TK1) falls below the detection limit after 4 weeks of treatment
Plasma
PK Cohort - Treatment Cohort - Endocrine sensitive disease rate based on Ki-67 percent after 4 weeks of treatment
Treatment Cohort - Endocrine sensitive disease rate based on Ki-67 percent after 4 weeks of treatment
Week 25
Treatment Cohort - Actual Conversion Rate
Treatment Cohort - Class of Residual Cancer Burden at time of surgery
Treatment Cohort - Pathologic Complete Response per American Joint Committee on Cancer staging system at time of surgery
Treatment Cohort - Rate of Pre-Operative Endocrine Prognostic Index at time of surgery
Week 12
Treatment Cohort - Overall Response Rate according to World Health Organization Criteria assessed by MRI at Week 12
Week 24
Treatment Cohort - Overall Response Rate according to World Health Organization Criteria assessed by MRI at Week 24
Week 24
Cholesterol
Treatment Cohort - Change from pre-neoadjuvant treatment in estrone (E1)/estradiol(E2)
Week 28
Both Cohorts - Incidence of Adverse Events Leading to Discontinuation
Both Cohorts - Incidence of Adverse Events assessed by CTCAE version 5.0
Both Cohorts - Incidence of Serious Adverse Events assessed by CTCAE version 5.0
Days 1 and 28
PK Cohort - Accumulation and accumulation half-life
PK Cohort - Area under the plasma (E)-endoxifen concentration-time curve from time zero to last measurable concentration
PK Cohort - Area under the plasma (Z)-endoxifen concentration-time curve from time zero to last measurable concentration
Week 25
Treatment Cohort - Conversion Rate
up to 28 days
PK Cohort - (E)-endoxifen steady-state clearance
PK Cohort - (Z)-endoxifen steady-state clearance
PK Cohort - Maximum plasma (E)-endoxifen concentration
PK Cohort - Maximum plasma (Z)-endoxifen concentration
PK Cohort - Time to plasma (E)-endoxifen maximum concentration
PK Cohort - Time to plasma (Z)-endoxifen maximum concentration

Trial Safety

Safety Progress

2 of 3
This is further along than 68% of similar trials

Trial Design

5 Treatment Groups

Treatment Cohort Arm 2 Initial Regimen
1 of 5
PK Cohort
1 of 5
Treatment Cohort Arm 1 Initial Regimen
1 of 5
Treatment Cohort Arm 1 Modified Regimen
1 of 5
Treatment Cohort Arm 2 Modified Regimen
1 of 5

Active Control

Experimental Treatment

174 Total Participants · 5 Treatment Groups

Primary Treatment: PK Cohort · No Placebo Group · Phase 2

PK Cohort
Drug
Experimental Group · 1 Intervention: Z-endoxifen · Intervention Types: Drug
Treatment Cohort Arm 1 Initial Regimen
Drug
Experimental Group · 1 Intervention: Z-endoxifen · Intervention Types: Drug
Treatment Cohort Arm 1 Modified RegimenExperimental Group · 2 Interventions: goserelin, Z-endoxifen · Intervention Types: Drug, Drug
Treatment Cohort Arm 2 Modified RegimenExperimental Group · 2 Interventions: goserelin, Z-endoxifen · Intervention Types: Drug, Drug
Treatment Cohort Arm 2 Initial RegimenActiveComparator Group · 2 Interventions: exemestane, goserelin · Intervention Types: Drug, Drug
Treatment
First Studied
Drug Approval Stage
How many patients have taken this drug
goserelin
1999
Completed Phase 3
~3980

Trial Logistics

Trial Timeline

Screening: ~3 weeks
Treatment: Varies
Reporting: baseline assessment up to cycle 3 (each cycle is 28 days) or up to 12 weeks

Who is running the clinical trial?

Atossa Therapeutics, Inc.Lead Sponsor
7 Previous Clinical Trials
423 Total Patients Enrolled
InClinUNKNOWN
Matthew P Goetz, MDPrincipal InvestigatorMayo Clinic

Eligibility Criteria

Age 18+ · Female Participants · 8 Total Inclusion Criteria

Mark “Yes” if the following statements are true for you:
You agree to use one non-hormonal highly effective method of contraception for the entire duration of study participation.
The tumor must be larger than 2.0 cm in diameter.