Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Goserelin

Antineoplastic Agents, Hormonal

Patients of the group will receive (neo)chemotherapy plus GnRHa ( Goserelin 3.6mg will be administered every 28 days by subcutaneous injection starting at least 7-14 days before the first cycle of chemotherapy and continued throughout chemotherapy duration).

Patients of the group will receive (neo)chemotherapy merely.

In goserelin group, goserelin 3.6mg will be administered every 28 days by subcutaneous injection starting at least 7-14 days before the first cycle of chemotherapy and continued throughout chemotherapy duration.

Goserelin 3.6 MG

Siyuan Wang

Houpu Yang

Fang Wang

Shu Wang

The purpose of this study is to assess efficacy of gonadotropin-releasing hormone agonist (goserelin) on the preservation of ovarian reserve function in young breast cancer patients treated with (neo)adjuvant chemotherapy by serial measuring ovarian reserve markers (AMH and AFC.etc) before and after chemotherapy and long-term pregnancy outcomes. Meanwhile, to evaluate the safety of this protective approach in young breast cancer patients by disease-free survival (DFS) and overall survival (OS) outcomes.

6.6-12% of women with breast cancer were diagnosed before the age of 40 year and breast cancer accounted for 40% of all cancer in women before the age of 40 year.Attributed to improved treatment, of which chemotherapy plays a major role, more than 70% of breast cancer patients at reproductive age obtain 10-year survival rates. Consequently, the question of pregnancy and premature ovarian failure after breast cancer treatment are presented more frequently. Fortunately, most of the available literature provides good evidence that pregnancy after breast cancer may improve survival. Unfortunately, no therapy has been shown to preserve fertility in patients receiving chemotherapy so far, although chemotherapy induced ovarian failure ,which finally results in infertility and premature ovarian failure, has been reported 60 years before. The greater rate of prepubertal than of postpubertal women with normal ovarian function after chemotherapy supports the concept that the suppressed ovary has a greater tolerance during cytotoxic treatments.While inhibiting the pituitary ovarian axis, Gonadotropin-releasing hormone agonist (GnRHa) is thought to block follicular development and reduce chemotherapy toxicity. Several studies had revealed GnRHa co-treatment yielded a statistically significant improvement in the proportion of spontaneous menstrual resumption after chemotherapy, compared to controls.It is noteworthy that menses and fertility are not necessarily linked. Absence of regular menses, particularly if the patient is taking tamoxifen(endocrine therapy for breast cancer), does not necessarily imply lack of fertility. Conversely, the presence of menses does not guarantee fertility.Currently, anti-Müllerian hormone(AMH) is considered as the best biochemical marker for assessment of reproductive capacity in reproductive medicine settings. Because it is produced by granulosa cells of growing antral follicles, AMH is significant positive correlation with both quantity and quality of oocytes. Moreover, it can be measured on any day for minimal fluctuation during the menstrual cycle.Antral follicle count (AFC) by vaginal ultrasound is also a good predictor of response to exogenous FSH and correlates independently with the number of oocytes retrieved during in vitro fertilization(IVF). Our study is designed to make sure the effect of GnRHa on the preservation of ovarian reserve function in breast cancer patients at reproductive age treated with (neo)adjuvant chemotherapy by observing the dynamic changes of ovarian reserve marker (AMH, AFC, E2 and FSH) pre and post chemotherapy and long-term pregnancy outcomes. Meanwhile, to evaluate the safety of this protective approach in young breast cancer patients by disease-free survival (DFS) and overall survival (OS) outcomes, and objective response rate(ORR) and pathological complete response (pCR) rate (for patitents treated with neoadjuvant chemotherapy). Finally, to explore whether patients with GnRH receptor or androgen receptor over-expression could benefit survival from this approach.

Patients: Premenopausal patients aged 18-45 years were eligible for enrollment, with stages I to III of newly diagnosed breast cancer, for which treatment with adjuvant or neoadjuvant chemotherapy was planned. Exceptions were made up of the use of hormonal contraception, previous chemotherapy, bilateral oophorectomy or ovarian irradiation before enrollment, and GnRHa -containing endocrine therapy planned.

Study Design: In our study, patients will be informed comprehensively and assigned without interference to receive either (neo)adjuvant chemotherapy with goserelin (goserelin group) or without goserelin (chemotherapy group) as their own selection. AMH, follicle stimulating hormone (FSH), and estradiol (E2) are used as biochemical markers and AFC is used as biophysical marker. The markers and menstrual status will be evaluated before, during, and at 0.5-year, 1-year, 2-year after chemotherapy. Additionally, pregnancy and disease related outcomes within 5 years, assessed annually.

Patients in goserelin group are given a subcutaneously dose of 3.6 mg (Zoladex, AstraZeneca) at least 1 week before the first cycle of chemotherapy and then every 4 weeks for the duration of chemotherapy. Subgroup analysis is stratified by age (≤ 40 years and 41-45 years), baseline level of AMH(≤1ng/ml and \>1ng/ml), chemotherapy regimen (AC, AC-T(H), others) and endocrine therapy regimen (with or without Tamoxifen).

The primary end point is to compare the recovery rate of AMH value (≥ 0.5ng/ml) (according to the "the Bologna criteria") between the two treatment groups at 2-year after chemotherapy. Secondary endpoints included descriptions of the dynamic changes of each marker from pre- to post-chemotherapy and time to resumption of menstrual activity (reappearance of two consecutive menstrual periods within 21 to 35 days); recovery rate of AMH value at 1 year and the rates of the other markers returning to the premenopausal range (E2 ≥ 40 pg/ml, FSH \< 25 U/L, AFC ≥ 5) were assessed at both 1 year and 2 years. Additional end points included pregnancy and disease related outcomes within 5 years, assessed annually. Events in the analysis of disease-free survival (DFS) included local recurrence, distant metastases, contralateral or ipsilateral breast tumor, second primary malignancy, and death due to any cause. Events in the analysis of overall survival (OS) included deaths due to any cause. Explore whether patients with GnRH receptor or androgen receptor over-expression could benefit survival by subtype analysis.

Statistical Analysis: Sample size calculation was based on the GBG 37 ZORO study. Out of 60 patients, 17 were accessible for AMH assessment during follow up to estimate ovarian function in 24 months after end of chemotherapy. Out of these 17 patients, 8 received goserelin and 9 were treated without goserelin. Recovery to normal AMH level was seen in 3 of 9 (33%) patients in chemotherapy group vs 4 of 8 (50%) patients in goserelin group respectively. To have 80% power to detect a 17% improvement in recovery to normal AMH level in 2 years, with a two-sided type I error rate of 0.05, 230 patients were needed to be assigned (calculated by NCSS-PASS). Finally, considering dropping off of patients, the target enrollment was 240 eligible patients. Descriptive statistics of baseline demographics and clinicopathologic characteristics were considered in the two treatment groups.The recovery rates of ovarian reserve markers and menses at 1-year and 2-year follow-up after chemotherapy were compared by a Pearson chi-square test. Logistic regression was performed to study the effect of age, baseline level of AMH, chemotherapy regimen and tamoxifen possible interactions on the probability of ovarian recovery. The differences in the baseline clinicopathological characteristics between the two groups were adjusted through propensity score weighting. The propensity score for each patient was estimated by a logistic regression model using group (the chemotherapy group or the goserelin group) as dependent variable and all patient characteristics as independent variables. Next, adjusted recovery rates of these markers and menses were compared by the chi-square test. Hormone concentrations and AFC at each time point were compared using the Mann-Whitney test. Log-rank statistics was used to compare time to return of menses between the two groups. Finally, Kaplan-Meier curve for disease-free will be calculated and compared by log-rank test. P values less than 0.05 are considered statistically significant. Analyses are performed by using SPSS version 18 software.

In summary: our study is the first prospective cohort study that focus on the premenopausal breast cancer patients who would like to preserve the ovarian function in China. The results will be more adaptable in China and other countries in Asia where breast cancer patients' age at diagnosis is younger. The outcome of this study may offer breast cancer patients at reproductive age hope of becoming mothers and possessing vigour of youth.

Recent breast cancer treatment guidelines strongly recommended that moderate and high-risk young patients with hormone receptor-positive disease should receive ovarian function suppression as part of adjuvant endocrine therapy, based largely on the results of the SOFT and TEXT Trials. Consequently, more than 20% patients in the two treatment group in this study who had hormone receptor-positive disease were estimated to directly receive or to change from tamoxifen to a GnRHa-containing endocrine therapy regimen and would not be assessed at the 2-year follow-up after chemotherapy. Therefore, an interim statistical analysis was determined to perform on the eligible patients who could be evaluated at 1 year after chemotherapy in the two treatment groups. The cutoff date for this analysis was November 30, 2019.

Study of Preservation of Ovarian Reserve During Chemotherapy for Young Breast Cancer Patients

Effect of Goserelin on the Protection of Ovarian Reserve During (Neo)Adjuvant Chemotherapy for Young Breast Cancer Patients: A Prospective Cohort Trial

When menses are regular, the optimal date of phlebotomy is on day 2-5 during the cycle.

AMH can be measured on any day during the menstrual cycle.Serum AMH concentrations will be measured using the AMH Gen II ELISA, according to the manufacturer's instructions

reappearance of two consecutive menstrual periods within 21 to 35 days after chemotherapy

Events in the analysis of disease-free survival include local recurrence, distant metastases, contralateral or ipsilateral breast tumor, second primary malignancy, and death due to any cause.

Events in the analysis of overall survival included deaths due to any cause.

Pregnancy event after chemotherapy in both groups.

AFC by ultrasound per vagina will be performed by the physician from Peking University People's Hospital Reproductive Medicine Center. AFC for virginity will be performed by ultrasound per rectum. The optimal date of measuring AFC is the days after menstruation.

Peking University People's Hospital

Nothing

Fulvestrant

Palbociclib

Estrogens

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormones

Hormone Antagonists

Protein Kinase Inhibitors

Enzyme Inhibitors

+ Goserelin 3.6 mg if pre or peri menopausal patient - duration 4 months

All patients in all arms will receive Fulvestrant 500mg

Fulvestrant 500mg

Palbociclib 125mg

Placebos

Jean-Marc Nabholtz, MD

This is a multicenter, international, double-blind randomized Phase III study to evaluate the pathological complete response (pCR) according to Chevalier classification between Fulvestrant® and the combination of Fulvestrant® plus Palbociclib as neoadjuvant therapy of hormone-sensitive patients with operable luminal breast cancer.

Eligible patients will be assessed upfront using the OncotypeDX® molecular test (Recurrence Score \<31).

This is a multicenter, international, double-blind, randomized study.

Eligible patients based on inclusion/exclusion criteria will be assessed using OncotypeDX molecular test. Patients with low/intermediate risk (Recurrence Score \<31) will be treated with the induction neoadjuvant Fulvestrant (500 mg (milligram) intra muscular(i.m) at Day 1, 14 and 28 and then every 4 weeks), plus Goserelin (3.6 mg subcutaneous (s.c) every 4 weeks, only for pre and peri-menopausal patients) for 4 months, followed by clinical and radiological assessment of the disease response.

Patients with objective response or stabilization will be randomized and treated for 4 additional months with:

* Fulvestrant 500 mg i.m every 4 weeks (+ Goserelin 3.6 mg s.c every 4 weeks, only for pre and peri-menopausal patients) and Placebo

or

* Combination Fulvestrant 500 mg i.m every 4 weeks (+ Goserelin 3.6 mg s.c every 4 weeks, only for pre and peri-menopausal patients) and Palbociclib 125 mg per os daily, 3 weeks on and 1 week off.

Patients with documented progressive disease will be considered at the discretion of the investigator for surgery or neoadjuvant chemotherapy. The preferred chemotherapy protocol will be FEC 100 -Taxotere (5fluorouracil 500mg/m2, Epirubicin 100 mg/m2, cyclophosphamide 500 mg/m2 (FEC) q3 weeks for 3 cycles followed by Docetaxel 100 mg/m2 (T) q 3 weeks for 3 cycles) for a total of 6 cycles with clinical and radiological assessment after each 3 cycles of chemotherapy (CT). Chemotherapy candidates will as well undergo surgery. The expected interval between the cycles will be 21 days, unless the patient has not recovered from toxicity. Specific dose adjustments will be set out in the protocol.

Breast and nodal surgery will be performed at completion of therapy (8 months of hormonal therapy for responding patients and 6 additional cycles of CT for non-responders). The type of surgery will be left at the discretion of the investigators.

Radiation therapy and adjuvant systemic treatment and endocrine therapy will be as well left at the discretion of the investigators.

Patients will be followed every 6 months during 5 years post surgery.

Fulvestrant Versus Fulvestrant Plus Palbociclib in Operable Breast Cancer Responding to Fulvestrant

Multicentre, International Neoadjuvant Randomized Double-blind Trial Comparing Fulvestrant® to a Combination of Fulvestrant® and Palbociclib (CDK 4/6 Inhibitor) in Patients With Operable Luminal Breast Cancer Responding to Fulvestrant®

pathological complete response will be assessed according to Le Chevalier's classification between two arms

pathological complete response will be assessed according to Sataloff's classification between two arms

radiological response according to the WHO criteria (US/Mammography/MRI)

Rate of breast conservative surgery will be assessed and compared between two arms

Safety and tolerability will be assessed in terms of adverse events (AEs), laboratory data and vital signs. Treatment-related adverse events will be assessed by using CTCAE v4.1 classification

Evaluation and comparison of Disease Free Survival (DFS) and Overall Survival (OS) between two arms

AstraZeneca

Pfizer

Genomic Health®, Inc.

International Cancer Research Group, United Arab Emirates

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Intensity modulated radiation therapy (IMRT), with 50 Gy in 25 daily fractions (2 Gy/fraction, 5 fractions weekly) for 5 weeks (week 1 - week 5).

Gosereline 3.6mg sc injection at week 1, week 5, and week 9

Gosereline 3.6mg sc injection at week 1, week 5, and week 9

Intensity modulated radiation therapy (IMRT), with 50 Gy in 25 daily fractions (2 Gy/fraction, 5 fractions weekly) for 5 weeks (week 1 - week 5).

radiation therapy

Eligible patients will undergo robotic-assisted radical prostatectomy and pelvic lymph node dissection

radical prostatectomy

Chi-Shin Tseng, MD

Shi-Wei Huang, PhD

Chao-Yuan Huang, MD, PhD

RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Androgens can stimulate the growth of prostate cancer cells. Hormone therapy can fight prostate cancer by androgen deprivation. It is not yet known if neoadjuvant radiation therapy is a more effective therapy for high-risk prostate cancer.

PURPOSE: Two-stage randomized trial to compare the effectiveness and safety of neoadjuvant radiotherapy and hormone therapy followed by radical prostatectomy in men with high-risk locally advanced prostate cancer

PRIMARY OBJECTIVE:

I. Success rate of salvage radiation therapy (SRT) measured as pathologic complete response (pCR) or pathologic near complete response (minimal residual disease, MRD) rate.

SECONDARY OBJECTIVES:

I. PSA decline rate after neoadjuvant treatment, rate of undetectable PSA after RP, rate of positive surgical margin, and rate of pathologic down-staging (≤ ypT2N0) II. Biochemical recurrence-free survival rate (from date of randomization). III. Metastasis free survival. IV. Prostate Cancer Death. V. Overall Survival

OUTLINE: Participants are randomized to 1 of 2 arms.

ARM I: Participants receive neoadjuvant hormone and radiation therapy, and then radical prostatectomy

ARM II: Participants receive neoadjuvant hormone therapy, and then radical prostatectomy.

After intervention, participants are followed up periodically for up to 20 years.

Neoadjuvant Hormone and Radiation Therapy Followed by Radical Prostatectomy in Patients With High-Risk Prostate Cancer

Neoadjuvant Hormone and Radiation Therapy Followed by Radical Prostatectomy in Patients With High-Risk Locally Advanced Prostate Cancer and Biomarker Research

pathologic complete response (pCR) or pathologic near complete response (minimal residual disease, MRD) rate

PSA decline is defined as nadir PSA value/baseline PSA value × 100

Complete response is defined as a drop in PSA on protocol treatment to less than 0.2 ng/ml.

Biochemical recurrence is defined as a rise in PSA to 0.2 ng/mL and a confirmatory value of 0.2 ng/mL or greater following radical prostatectomy

Distant failure rate is estimated by the cumulative incidence method, with failure defined as the first occurrence of distant failure.

Prostate cancer death rate us estimated by the cumulative incidence method, with failure defined as death due to prostate cancer or complications of trial.

Overall survival is estimated by the Kaplan-Meier method, with failure defined as death by any cause.

Progress-free survival is estimated by the Kaplan-Meier method, with failure defined as the first occurrence of PSA failure, local, regional or distant failure, or death from any cause.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of Preservation of Ovarian Reserve During Chemotherapy for Young Breast Cancer Patients	NCT02430103	Breast Cancer	Goserelin 3.6 M...	18 Years - 45 Years	Peking University People's Hospital
Fulvestrant Versus Fulvestrant Plus Palbociclib in Operable Breast Cancer Responding to Fulvestrant	NCT03447132	Breast Neoplasm...	Fulvestrant 500... Palbociclib 125... Goserelin 3.6 M... Placebos	18 Years -	International Cancer Research Group, United Arab Emirates
Study of Preservation of Ovarian Reserve During Chemotherapy for Young Breast Cancer Patients	NCT02430103	Breast Cancer	Goserelin 3.6 M...	18 Years - 45 Years	Peking University People's Hospital
Neoadjuvant Hormone and Radiation Therapy Followed by Radical Prostatectomy in Patients With High-Risk Prostate Cancer	NCT04894188	Prostate Cancer	radiation thera... Goserelin 3.6 M... radical prostat...	20 Years - 75 Years	National Taiwan University Hospital

Spots Global Cancer Trial Database for goserelin 3.6 mg