Neoplasms

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Breast Neoplasms

Recurrence

Breast Diseases

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All Drugs and Chemicals

Letrozole

Estrogens

Palbociclib

Goserelin

Aromatase Inhibitors

Enzyme Inhibitors

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormones

Hormone Antagonists

Protein Kinase Inhibitors

Antineoplastic Agents, Hormonal

Oncotype DX Breast recurrence score on diagnostic tissue

Daily Letrozole for 24 weeks + Palbociclib daily for 24 weeks + Goserelin weekly for 24 weeks

Letrozole 2.5 mg by mouth daily for 24 weeks

Palbociclib 125mg by mouth daily for 21 days per 28-day cycle (21 days on, 7 days off) for 24 weeks

Goserelin 3.6mg subcutaneous injection x 1 on Day 1 of each 28-day cycle for 24 weeks

Prior to assignment to Arm 1 the Oncotype DX diagnostic test will be conducted on diagnostic tissue to assign a recurrence score for stratification to cohort 1 or 2.

Oncotype DX Breast Recurrence Score

Norman Wolmark, MD

This study will look at the safety and effectiveness of the combination of palbociclib and letrozole and ovarian suppression for premenopausal patients who have ER-positive/HER2-negative breast cancer that has not yet been treated.

NSABP FB-13 is a phase II, open label study to examine the biological and clinical effect of neoadjuvant endocrine therapy with letrozole, palbociclib and ovarian suppression in premenopausal patients with estrogen-receptor (ER) positive, HER2-negative, early invasive breast cancer.

Premenopausal women newly diagnosed with ER-positive/HER2-negative early breast cancer who are suitable candidates for neoadjuvant endocrine therapy will be invited to join the FB-13 trial. A screening Oncotype DX Breast Recurrence Score® will be performed by Genomic Health, Inc. (GHI) on the diagnostic tissue of consenting patients to verify eligibility.

Patients will be stratified into one of two approximately equal sized cohorts based on baseline Breast Recurrence Score (RS) (cohort 1: patients with RS less than 11 or cohort 2: patients with RS 11 to less than 26).

Patients in both cohorts will receive letrozole 2.5 mg by mouth daily, palbociclib 125 mg by mouth daily for 21 days of a 28 day cycle, and goserelin 3.6 mg subcutaneous injection on Day 1 of each 28 day cycle. At Week 6 of study therapy, patients will have two core-cut biopsies. Patients from both cohorts who have a Ki67 less than 10% level will continue receiving study therapy for a total of 6 cycles. Patients with a persistent Ki67 greater than or equal to 10% at week 6 will permanently discontinue study therapy and begin neoadjuvant chemotherapy or proceed to surgery at the discretion of the treating physician.

Pre-treatment samples and post-surgical samples will be collected and analysed to identify subgroups of patients who may derive the most clinical benefit. The results of the biological analyses may allow a target sensitive population to be selected for future trials. The tissue collected in FB-13 will form an integral part of the primary analyses; so all core biopsies in this trial will be mandated for patients.

Two core-cut biopsies will be collected from each patient at baseline, after 6 weeks of study therapy, and upon completion of study therapy (24 weeks) at the time of definitive surgery.

Blood samples will be collected at baseline, 4 weeks, and at 24 weeks for estrone and estradiol levels to demonstrate ovarian suppression. A 4-week estradiol level in the postmenopausal range will be required to receive further treatment on study.

Biological and Clinical Effects of Palbociclib With Ovarian Suppression and Letrozole in the Neoadjuvant Treatment of Breast Cancer

An Assessment of the Biological and Clinical Effects of Palbociclib (PD 0332991) With Ovarian Suppression and Letrozole in the Neoadjuvant Treatment of Patients With Premenopausal Estrogen-Receptor Positive/HER2-Negative Primary Breast Cancer

Percentage of patients with a Ki67 less than 2.7%

Objective response rate determined by breast tumor assessment measured by clinical exam and ultrasound

Percentage of patients with absence of invasive cancer in surgical specimens

Correlation of the Oncotype DX Breast Recurrence Score® with clinical Complete Response

Correlation of the Oncotype DX Breast Recurrence Score® with pathologic Complete Response

Correlation of the Oncotype DX Breast Recurrence Score® with Complete Cell cycle arrest rate

Changes between surgical intent declared at study start and actual surgery received after treatment

Compare the estrone level at baseline to that after neoadjuvant treatment

Compare the estradiol level after neoadjuvant treatment

Genomic Health®, Inc.

Pfizer

NSABP Foundation Inc

Bone Density Conservation Agents

Pharmaceutical Solutions

Reproductive Control Agents

Tamoxifen

Exemestane

Leuprolide

Anastrozole

Selective Estrogen Receptor Modulators

Estrogen Receptor Modulators

TOL2506 in combination with standard endocrine therapy (Tamoxifen \& Aromatase Inhibitors)

Leuprolide Acetate for injectable suspension, 30 mg. Subcutaneous injection every 3 months

TOL2506

20 mg once daily or 10 mg 2 times daily - either tablet of solution

One 2.5 mg tablet taken orally once daily

Letrozole tablets

Anastrozole Tablets

Exemestane Tablets

TOL2506A (OVELIA) is a Phase 3, single arm, open-label study evaluating the effectiveness of TOL2506 in suppressing ovarian function in premenopausal women with HR+, HER2-negative breast cancer and men with HR+ breast cancer. The TOL2506A-EXT study described here is a safety extension study to assess and collect long-term data on the ongoing safety and tolerability of TOL2506 in combination with tamoxifen or an AI for up to 4 years.

Safety Extension Study for Subjects With HR+, HER2- Breast Cancer for Subjects Who Have Completed the OVELIA Study

Open-label, Safety Extension Study for Subjects With HR+, HER2-Negative Breast Cancer Who Have Completed the OVarian Suppression Evaluating Subcutaneous LeuprolIde Acetate in Breast Cancer OVELIA Study

Tolmar Inc.

Mitogens

TOL2506 in combinatination with standard endocrine therapy (Tamoxifen \& Aromatase Inhibitors)

Leuprolide Acetate for injectable suspension, 30 mg. Subcutaneous injection every 3 months.

20 mg once daily or 10 mg 2 times daily - either tablet or solution

Letrozole Tablets

A Mehta

C Fajardo

E P Hamilton

This is a phase 3, single arm, open-label study evaluating the effectiveness of TOL2506 to suppress ovarian function in premenopausal women with HR+, HER2-negative breast cancer. The study will also aim to assess the safety of TOL2506 in men with HR+, HER2-negative breast cancer. The Screening Period will be conducted in two parts: 1) an abbreviated, initial screening where premenopausal status will be determined prior to neoadjuvant or adjuvant chemotherapy (if planned) and 2) the full screening assessment conducted after neoadjuvant or adjuvant chemotherapy (or for subjects who enter the study without having received chemotherapy). Following the Screening Period, eligible subjects will enter into the 48 week Treatment Period in 1 of 2 groups: those who will receive tamoxifen concurrently with TOL2506 or those who will initiate therapy with an AI (letrozole, anastrozole, or exemestane) beginning 6 weeks after the first administration of TOL2506, upon confirmation that estradiol (E2) levels of \< 20 pg/mL (testosterone levels \< 50 ng/dL in males) have been achieved. After Week 12, subjects will be allowed to switch from receiving an AI to receiving tamoxifen or from tamoxifen to AI at the discretion of the Investigator. However, a switch is not permitted 28 days prior to a dosing visit (eg, Week 24, 36, and 48 where a pre-dose blood sample for PK and PD analysis will be drawn). At the end of the Treatment Period, upon completion of the End of Study Visit (Visit 9, Week 48) subjects may be eligible to participate in a Safety Extension Study under a separate Protocol.

Ovarian Suppression Evaluating Subcutaneous Leuprolide Acetate in Breast Cancer

Phase 3,Single Arm,Open-Label Study Evaluating Ovarian Suppression Following 3 Month Leuprolide Acetate For Injectable Suspension (TOL2506) in Combination With Endocrine Therapy in Premenopausal Subjects With Hormone-Receptor-Positive (HR+),Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Breast Cancer

Percent of all subjects with LH \< 4 IU/L, E2 \<20 pg/mL in subjects treated with TOL2506 + endocrine therapy (tamoxifen or aromatase inhibitors) at every measurement from Week 6 to Week 48

Percent of all subjects with LH \< 4 IU/L, E2 \<20 pg/mL in subjects treated with TOL2506 + tamoxifen at every measurement from Week 6 to Week 48

Percent of all subjects with LH \< 4 IU/L, E2 \<20 pg/mL in subjects treated with TOL2506 + aromatase inhibitor at every measurement from Week 6 to Week 48

Menopause

After signing informed consent, patients will be screened, eligible patients were randomly divided into 2 groups, the test group should use Zoladex 3.6mg once a month up to 2-3 years combined with chemotherapy,all patients will receive Tamoxifen after chemotherapy

After signing informed consent, patients will be screened, eligible patients were randomly divided into 2 groups, the control group should use Zoladex 3.6mg once a month up to 2-3 years after chemotherapy,all patients will receive Tamoxifen after chemotherapy

Eligible patients were randomly divided into 2 groups, the intervention group should use Zoladex 3.6mg once a month up to 2-3 years combined with chemotherapy,and the control group should use chemotherapy alone followed by Zoladex

Zoladex

Zhi-Min Shao, MD

The present study is a randomized open-label -phase III study that aims to compare the efficacy and safety of the adjuvant chemotherapy with simultaneous or sequential application of Zoladex up to 2-3 years for ≤ 45 year old premenopausal hormone receptor-positive breast cancer.

Data showed that ovarian suppression therapy may protect the ovarian function in premenopausal patients received chemotherapy for breast cancer. However this is still a controversial issue. Sequential use of GnRHa (Zoladex) as ovarian suppression treatment after chemotherapy has been established as an effective endocrine therapy for ER positive premenopausal breast cancer. The present study is a randomized open-label phase III study that aims to observe the efficacy and safety of the adjuvant chemotherapy with simultaneous combination of Zoladex up to 2-3years and chemotherapy compared with the sequential schedule in ≤ 45 year old premenopausal hormone receptor-positive breast cancer patients.

Simultaneous Versus Sequential Use of Adjuvant Chemotherapy and GnRHa in Treating ER+,Premenopausal Breast Cancer

A Phase III,Randomized,Open Label Study Comparing Simultaneous Versus Sequential Use of Adjuvant Chemotherapy and GnRHa up to 2-3 Years for ≤ 45 Year Old Pre-menopausal Hormone Receptor-positive Breast Cancer

the Resumption that patients recover the natural menstrual or serum E2, FSH, LH return to the premenopausal range within 1 year after stopping Zoladex

Relapse free survival (RFS): RFS related events ware defined as local-regional recurrence, distant metastasis or death, whichever occurred first.during follow up

Other adverse events (Gynecological events, blood lipids, thrombosis, cardiovascular diseases, and etc.)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Biological and Clinical Effects of Palbociclib With Ovarian Suppression and Letrozole in the Neoadjuvant Treatment of Breast Cancer	NCT03628066	Breast Cancer	Letrozole Palbociclib Goserelin Oncotype DX Bre...	18 Years -	NSABP Foundation Inc
Safety Extension Study for Subjects With HR+, HER2- Breast Cancer for Subjects Who Have Completed the OVELIA Study	NCT05645536	Breast Cancer	TOL2506 Tamoxifen Letrozole table... Anastrozole Tab... Exemestane Tabl...	18 Years - 51 Years	Tolmar Inc.
Ovarian Suppression Evaluating Subcutaneous Leuprolide Acetate in Breast Cancer	NCT04906395	Breast Cancer	TOL2506 Tamoxifen Letrozole Table... Anastrozole Tab... Exemestane Tabl...	18 Years - 49 Years	Tolmar Inc.
Safety Extension Study for Subjects With HR+, HER2- Breast Cancer for Subjects Who Have Completed the OVELIA Study	NCT05645536	Breast Cancer	TOL2506 Tamoxifen Letrozole table... Anastrozole Tab... Exemestane Tabl...	18 Years - 51 Years	Tolmar Inc.
Ovarian Suppression Evaluating Subcutaneous Leuprolide Acetate in Breast Cancer	NCT04906395	Breast Cancer	TOL2506 Tamoxifen Letrozole Table... Anastrozole Tab... Exemestane Tabl...	18 Years - 49 Years	Tolmar Inc.
Simultaneous Versus Sequential Use of Adjuvant Chemotherapy and GnRHa in Treating ER+,Premenopausal Breast Cancer	NCT01712893	Breast Cancer	Zoladex	- 45 Years	Fudan University

Spots Global Cancer Trial Database for ovarian suppression