Neoplasms

All Conditions

Skin and Connective Tissue Diseases

Carcinoma

Breast Neoplasms

Carcinoma, Ductal

Carcinoma in Situ

Carcinoma, Lobular

Carcinoma, Intraductal, Noninfiltrating

Breast Carcinoma In Situ

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Breast Diseases

Skin Diseases

Bone Density Conservation Agents

Antineoplastic Agents

All Drugs and Chemicals

Tamoxifen

Hormones

Estrogens

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormone Antagonists

Antineoplastic Agents, Hormonal

Estrogen Receptor Modulators

Selective Estrogen Receptor Modulators

Tamoxifen 10 mg (1 tablet) every other day for 6 months.

Tamoxifen 10 mg (1 tablet) every other day for 6 months + 5:2 diet (5 days/week at regular energy intake+2 days a week at an average 75% energy deficit)

Step counter device + 5:2 diet (5 days/week at regular energy intake+2 days a week at an average 75% energy deficit)

One tablet of Tamoxifen 10 mg every other day for 6 months

Tamoxifen 10 mg Tablet

"5:2 diet": 5 days a week at regular energy intake and 2 days/week at 75% energy deficit (diet will be restricted at 500-800 kcal corresponding to a 75% reduction compared to normal size)

Intermittent caloric restriction

Participants will receive personal advice on healthy lifestyle and a step counter

Step counter Device

Bernardo Bonanni, MD

Aliana Guerrieri-Gonzaga, MSc

Andrea DeCensi, MD

Matilde Pensabene, MD

Stefania Zovato, MD

Circulating levels of Sex Hormone Binding Globulin (SHBG) are significantly associated with a decreased risk of breast cancer.

The main aim of this clinical trial is to verify whether Low Dose Tamoxifen (LDT) increases circulating levels of SHBG more than lifestyle intervention (LI) with or without intermittent caloric restriction (ICR) after 6 months in women at increased risk of breast cancer (i.e., healthy participants carriers of a germline pathogenic/likely pathogenetic variant in at least one of the following genes: BRCA1, BRCA2, PALB2, ATM, CHEK2, CDH1, RAD51C or RAD51D, or with \> 5% breast cancer risk at 10 years, using the Tyrer Cuzick or the Breast Cancer Surveillance Consortium Risk models or with a recently resected intraepithelial neoplasia of the breast (IEN).

The secondary aims are:

* to verify whether ICR significantly modulates primary and secondary endpoints such as Homeostasis Model Assessment (HOMA) index, immune and inflammatory markers, lipid profile, Adiponectin/Leptin (A/L) ratio, quality of life (QoL), Body mass index (BMI), fat body composition, safety and toxicity;
* to verify whether LDT significantly modulates secondary endpoints, such as HOMA-index, immune and inflammatory markers, lipid profile, A/L ratio, QoL, BMI, fat body composition, safety and toxicity;
* to investigate differences in microbiome composition by arms and the effect of changes in microbiome on QoL taking into account circulating biomarkers, cytokines, immune modulators, and inflammatory proteins in serum;
* to investigate MD (Mammographic Breast Density) changes by LDT vs. LI, with or without ICR. This aim will be performed in a subgroup of participants (not all the participants will undergo mammography due to younger age).

Italian, multicenter, phase II, biomarker trial. A total of 200 women aged 18-70 years will be randomly assigned (1:1:1:1) to one of the four intervention arms Arm 1: Low dose Tamoxifen (LDT) i.e. 10 mg every other day; Arm 2: Low dose Tamoxifen (LDT) + Intermittent Caloric Restriction (ICR); Arm 3: Lifestyle intervention (LI) using a step counter; Arm 4: Lifestyle intervention (LI) using a step counter + Intermittent Caloric Restriction (ICR).

Participants will be stratified by center and by disease status (high risk vs. previous IEN) and intervention will last six months for all arms.

Low Dose TamOxifen and LifestylE Changes for bReast cANcer prevenTion

Low Dose TamOxifen and LifestylE Changes for bReast cANcer prevenTion: a Randomized Phase II Biomarker Trial in Subjects at Increased Risk

Sex hormone binding globulin level after 6 months of intervention

Ente Ospedaliero Ospedali Galliera

Istituto Oncologico Veneto IRCCS

Istituto Nazionale Tumori IRCCS - Fondazione G. Pascale

European Institute of Oncology

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

Niraparib

Poly(ADP-ribose) Polymerase Inhibitors

Enzyme Inhibitors

Patients receive niraparib PO QD on days 1-28. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Following completion of treatment, patients then undergo standard of care surgery.

Niraparib Tosylate Monohydrate

Radical Prostatectomy

Marc Dall'Era

This phase II trial studies how well niraparib, when given before surgery, works in treating patients with high risk prostate cancer that has not spread to other parts of the body (localized) and alterations in deoxyribonucleic acid (DNA) repair pathways. Niraparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PRIMARY OBJECTIVES:

I. To assess the impact of neoadjuvant niraparib tosylate monohydrate (niraparib) therapy prior to radical prostatectomy (RP) on pathologic tumor stage, frequency of lymph node metastases and positive margin rates for patients undergoing radical prostatectomy for high-risk, clinically localized prostate cancer with alterations in DNA repair pathways.

SECONDARY OBJECTIVE:

I. To assess 5-year biochemical recurrence in subjects with high-risk prostate cancer and DNA-damage response defects after prostatectomy.

OUTLINE:

Patients receive niraparib orally (PO) once daily (QD) on days 1-28. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Following completion of treatment, patients then undergo standard of care surgery.

After completion of study treatment, patients are followed up at 30 days, every 3 months for 2 years, and then every 6 months for up to 3 years.

Niraparib Before Surgery in Treating Patients With High Risk Localized Prostate Cancer and DNA Damage Response Defects

Phase II Trial of PARP Inhibitor Niraparib for Men With High Risk Prostate Cancer and DNA Damage Response Defects

The study will assess the impact of neoadjuvant niraparib therapy prior to radical prostatectomy (RP) on pathologic tumor stage, frequency of lymph node metastases and positive margin rates for patients undergoing radical prostatectomy for high-risk, clinically localized prostate cancer with alterations in deoxyribonucleic acid (DNA) repair pathways. Pathologic complete response (PCR) defined as no tumor identified on hematoxylin and eosin (H\&E) stained sections will be assessed; minimal residual disease (MRD) will be defined as tumor clusters limited to \< 5 mm and confined to prostate gland.

Exact 95% confidence intervals for pRR and other binary outcomes, adjusted for the two-stage design, will be calculated as described by Koyama and Chen. Response rates will be compared between patients with biallelic and monoallelic loss using Fisher's Exact Test.

Median biochemical progression free survival (bPFS) and quartiles (when reached) will be calculated from Kaplan-Meier estimates, and 95% confidence intervals will be calculated using Greenwood's formula.

National Cancer Institute (NCI)

Janssen, LP

Marc Dall'Era, MD

Principal Investigator

Gland and Hormone Related Diseases

Rare Diseases

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Ovarian Cancer

Ovarian Epithelial Cancer

Risk-reducing salpingectomy after the completion of childbearing with delayed oophorectomy.

* BRCA1: RRS at age 25-40 and RRO at a maximum age of 45 (advised between 35 and 45).
* BRCA2: RRS at age 25-45 and RRO at a maximum age of 50 (advised between age 40 and 50).
* BRIP1, RAD51C, RAD51D: RRS at age 25-50 and RRO at a maximum age of 55 (advised between 45 and 55)

Risk-reducing salpingectomy with delayed oophorectomy

* BRCA1 at a maximum age of 40 (advised between age 35 and 40)
* BRCA2 at a maximum age of 45 (advised between age 40 and 45)
* BRIP1, RAD51C, RAD51D: at a maximum age of 50 (advised between 45 and 50)

Risk-reducing salpingo-oophorectomy

Joanne A. de Hullu, MD, PhD

Karen H. Lu, MD, PhD

Karen Lu

Elizabeth Swisher

Martha Hickey

Maxime Fastrez

Susanne Housmans

Glauco Baiocchi

Myriam Perrone

Robert Fruscio

Claudia Marchetti

David Cantu

Caroline Vos, MD

Brigitte Slangen, MD, PhD

Jurgen M.J. Piek, MD, PhD

Luc van Lonkhuijzen, MD, PhD

Marc van Beurden, MD, PhD

Nathalie Reesink-Peters, MD, PhD

Marian Mourits, MD, PhD

Mirjam Apperloo, MD, PhD

Katja Gaarenstroom, MD, PhD

Marta Piso-Jozwiak, MD, PhD

Ronald Zweemer, Prof, MD, PhD

Sjors Coppus, MD, PhD

Arnold-Jan Kruse, MD, PhD

Anne Dorum

Maciej Stukan

Monika Bodjys-Szyndlar

Krzysztof Nowosielski

Agnieszka Rychlik

Angelique Flöter-Radestad

Santiago Scasso

Rosella P.M.G. Hermens, MD,PhD

Elizabeth M. Swisher, MD, PhD

The aim of the project is to evaluate the risk-reducing salpingectomy with delayed oophorectomy as an alternative for risk-reducing salpingo-oophorectomy in high risk women with respect to ovarian cancer incidence.

In BRCA1/2 gene mutation carriers, a risk-reducing salpingo-oophorectomy (RRSO) is recommended around the age of 40. This recommendation is based on a 10-40% life-time risk of ovarian cancer in this population and disappointing results of ovarian cancer surveillance for early detection. Moreover, the mortality rate of ovarian cancer is high. Effects of RRSO are a decrease in ovarian cancer risk (80-96%) on one hand and immediate onset of menopause and non-cancer related morbidity on the other hand. The fifty percent breast cancer risk reduction after RRSO has become disputable in the last years. Based on multiple studies showing that most high-grade serous ovarian cancers develop at the distal end of the Fallopian tube, an innovative strategy for RRSO has been developed for this study proposal: risk-reducing salpingectomy (RRS) with delayed risk-reducing oophorectomy (RRO). However, the safety of this strategy has not been proven yet. Before implementing this innovative strategy as standard care we need to investigate the long term effects on ovarian cancer incidence.

TUBectomy With Delayed Oophorectomy in High Risk Women to Assess the Safety of Prevention

TUBectomy With Delayed Oophorectomy as Alternative for Risk-reducing Salpingo-oophorectomy in High Risk Women to Assess the Safety of Prevention: TUBA-WISP II Study.

High grade serous (ovarian) cancer incidence

Incidence of (pre)malignant findings in tubes/ovaries at risk-reducing salpingectomy, oophorectomy and salpingo-oophorectomy.

Incidence of pelvic cancer (other than ovarian cancer)

Uptake of risk reducing oophorectomy after risk reducing salpingectomy

University Medical Center Nijmegen

Dr. J.A. de Hullu, MD, PhD

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Low Dose TamOxifen and LifestylE Changes for bReast cANcer prevenTion	NCT06033092	BRCA Mutation PALB2 Gene Muta... Ductal Carcinom... Lobular Carcino... ATM Gene Mutati... CHEK2 Gene Muta... CDH1 Gene Mutat... RAD51C Gene Mut... RAD51D Gene Mut...	Tamoxifen 10 mg... Intermittent ca... Step counter De...	18 Years - 70 Years	European Institute of Oncology
Low Dose TamOxifen and LifestylE Changes for bReast cANcer prevenTion	NCT06033092	BRCA Mutation PALB2 Gene Muta... Ductal Carcinom... Lobular Carcino... ATM Gene Mutati... CHEK2 Gene Muta... CDH1 Gene Mutat... RAD51C Gene Mut... RAD51D Gene Mut...	Tamoxifen 10 mg... Intermittent ca... Step counter De...	18 Years - 70 Years	European Institute of Oncology
Niraparib Before Surgery in Treating Patients With High Risk Localized Prostate Cancer and DNA Damage Response Defects	NCT04030559	ATM Gene Mutati... BRCA1 Gene Muta... BRCA2 Gene Muta... BRIP1 Gene Muta... CDK12 Gene Muta... CHEK1 Gene Muta... CHEK2 Gene Muta... DNA Damage Resp... DNA Repair Gene... FANCA Gene Muta... FANCD2 Gene Mut... FANCL Gene Muta... GEN1 Gene Mutat... NBN Gene Mutati... Prostate Carcin... RAD51 Gene Muta... RAD51C Gene Mut...	Niraparib Niraparib Tosyl... Radical Prostat...	18 Years -	University of California, Davis
Niraparib Before Surgery in Treating Patients With High Risk Localized Prostate Cancer and DNA Damage Response Defects	NCT04030559	ATM Gene Mutati... BRCA1 Gene Muta... BRCA2 Gene Muta... BRIP1 Gene Muta... CDK12 Gene Muta... CHEK1 Gene Muta... CHEK2 Gene Muta... DNA Damage Resp... DNA Repair Gene... FANCA Gene Muta... FANCD2 Gene Mut... FANCL Gene Muta... GEN1 Gene Mutat... NBN Gene Mutati... Prostate Carcin... RAD51 Gene Muta... RAD51C Gene Mut...	Niraparib Niraparib Tosyl... Radical Prostat...	18 Years -	University of California, Davis
TUBectomy With Delayed Oophorectomy in High Risk Women to Assess the Safety of Prevention	NCT04294927	BRCA1 Gene Muta... BRCA2 Gene Muta... RAD51C Gene Mut... RAD51D Gene Mut... BRIP1 Gene Muta... Ovarian Cancer	Risk-reducing s... Risk-reducing s...	25 Years - 50 Years	University Medical Center Nijmegen

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