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Breast Neoplasms

Breast Diseases

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Antioxidants

This study will investigate the null hypothesis that use of antioxidant supplements during adjuvant chemotherapy will have no impact on toxicities and disease-free, as well as overall, survival, and also evaluate the role of polymorphisms in genes related to oxidative stress in relation to treatment outcomes.

This study will enroll 3000 women from S0221with node positive or high-risk node-negative breast cancer receiving AC+T onto this ancillary study to address the following specific aims:

1. To characterize use of antioxidant supplements with a survey instrument prior to and at completion of treatment, and to evaluate reported use pre and post treatment in relation to toxicity and disease-free survival. The potential effects of diet, physical activity, and other lifestyle factors on relationships between supplement use and treatment outcomes will also be considered.
2. To evaluate if variants (polymorphisms) in genes that produce reactive oxygen species (ROS) (MPO) and in genes that protect cells from the effects of ROS are associated with treatment-related toxicities and with disease-free survival.

Antioxidant Supplements, Genetics and Chemotherapy Outcomes

Self administered questionnaire to evaluate use of antioxidant supplements in relation to toxicity

Polymorphisms will be determined by sequencing as described in detail on the National Cancer Institute'sSNP500Cancer database

Self administered questionnaire to evaluate use of antioxidant supplements in relation to disease free survival

Roswell Park Cancer Institute

Symptoms and General Pathology

Carcinoma

Neoplasm Micrometastasis

Neoplasm Metastasis

Neoplastic Processes

Antineoplastic Agents

Bone Density Conservation Agents

Reproductive Control Agents

Trastuzumab

Pertuzumab

Tamoxifen

Hormones

Exemestane

Letrozole

Leuprolide

Anastrozole

Antineoplastic Agents, Immunological

Aromatase Inhibitors

Enzyme Inhibitors

Estrogens

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormone Antagonists

Antineoplastic Agents, Hormonal

Selective Estrogen Receptor Modulators

Estrogen Receptor Modulators

Study treatment will be administered in 21-day (3- week, +/- 3 days) cycles for one year (18 cycles).

* Trastuzumab + Pertuzumab SC fixed dose combination
* Hormonal therapy- oral, daily per cycle (may add LHRH agonist per investigator discretion)

Trastuzumab + pertuzumab SC FDC (PHESGO) will be administered on Day 1 of each 21-day cycle , subcutaneous, fixed dose

Pertuzumab+TRASTUZUMAB

ADJUVANT ENDOCRINE THERAPY

Adrienne Waks, MD

K.M. Steve Lo, MD

K. M. Steve Lo, MD

Ashley Trumball

Jane Meisel, MD

Tarah Ballinger, MD

Tarah J Ballinger, MD

Laurie Lewis

Sarah J Sinclair, DO

Nadine Tung, MD

Natalie Sinclair, MD

Meredith Faggen, M.D.

Meredith Faggen, MD

Stefani Freeman, RN

Jeanna Walsh, MD

Breast Cancer Center

Sylvia Adams, MD

Julia Rauch, MD

Crissey Tait

Lisa Carey, MD

Julia Raugh, MD

Nicole Williams, MD

Denise A. Yardley, MD

Denise Yardley, MD

Vandana Abramson, MD

Pamela Lewis

Vicente Valero, MD

Adrienne C Waks, MD

This research study is studying a combination of HER2-directed therapies (trastuzumab and pertuzumab) and hormonal therapy as a treatment after surgery for hormone receptor positive breast cancer.

The study drugs involved in this study are:

* A combination of trastuzumab and pertuzumab given as an injection under the skin (PHESGO)
* Hormonal (endocrine) Treatment

The research study procedures include screening for eligibility and study treatment including laboratory evaluations, physical exams, questionnaires, and follow up visits.

* Participants will receive HER2-directed treatment for 1 year and hormonal therapy for approximately 5 years.
* It is expected that about 375 people will take part in this research study.

This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational drug combination to learn whether the drug works in treating a specific disease. "Investigational" means that the drug combination is being studied.

The drugs trastuzumab and pertuzumab are both monoclonal antibodies, which are disease-fighting proteins made by cloned immune cells. The U.S. Food and Drug Administration (FDA) has approved trastuzumab, pertuzumab, and trastuzumab + pertuzumab subcutaneous fixed dose combination (PHESGO) as treatment for HER2 positive breast cancer. The FDA has also approved hormonal therapies as treatment for hormone receptor positive breast cancer.

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A Single Arm Phase II Study of ADjuvant Endocrine Therapy, Pertuzumab, and Trastuzumab for Patients With Anatomic Stage I Hormone Receptor-positive, HER2-positive Breast Cancer

20-347 NCT Number Title A Single Arm Phase II Study of ADjuvant Endocrine Therapy, Pertuzumab, and Trastuzumab for Patients With Anatomic Stage I Hormone Receptor-positive, HER2-positive Breast Cancer (ADEPT)

The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to Sponsor Investigator or designee. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.

assessed by Voils questionnaire. Responses to survey items will be summarized using means or proportions depending on the nature of the questions.

The FACT-B includes the FACT-G, a 27-item generic cancer questionnaire and a 10- item breast cancer specific module. Responses to survey items will be summarized by means or proportions depending on the nature of the items

The Activity Level Scale Domain from the RSCL is an 8-item scale designed to measure whether the respondent can perform a series of activities at the present time. Items are summed to produce an overall score, with higher scores representing better functioning.

Responses to survey items will be summarized by means or proportions

The WPAI was created as a patient-reported quantitative assessment of the amount of absenteeism, presenteeism and daily activity impairment attributable to general health (WPAI:GH) or a specific health problem (WPAI:SHP). The 6 questions in the WPAI questionnaire were generated from three main sources Responses to survey items will be summarized by means or proportions depending on the nature of the items

There is increasing recognition of the profound importance of the financial strain on patients created by cancer diagnosis and therapies. The COST (Comprehensive Score for financial Toxicity) measure has been developed and validated as a mechanism to assess financial stress related to cancer diagnosis and treatment Responses to survey items will be summarized by means or proportions

The HPASQ-SC (Appendix C) is a tool to measure patient-reported outcomes regarding patient acceptance of subcutaneous therapy. It was developed and underwent validity testing in a cohort of patients receiving subcutaneous rituximab for lymphoma. The HPASQ-SC contains questions related to two main concepts (treatment satisfaction and impact of treatment administration) and eight sub-concepts: overall preference/satisfaction; convenience; confidence; bothersome-ness; physical impact; psychological impact; impact on activities of daily life; and impact on the interaction with healthcare providers.21

Responses to survey items will be summarized by means or proportions

Kaplan-Meier estimates of iDFS will be estimated and plotted with the corresponding 95% confidence intervals.

from the time of randomization until the occurrence of the first of the following events: invasive local/regional recurrence, Contralateral invasive breast cancer, Distant recurrence, Death from any cause

RFI will be estimated and plotted with the corresponding 95% confidence intervals, using Kaplan-Meier estimates for the study as a whole and for subgroups of patients determined by intrinsic subtype (HER2-enriched, luminal, basal Time of randomization until the occurrence of the first of the following events:Invasive local/regional recurrence, Distant recurrence, Death from breast cancer

defined as the time period between randomization and death due to breast cancer.

OS will be estimated and plotted with the corresponding 95% confidence intervals, using Kaplan-Meier estimates for the study as a whole and for subgroups of patients determined by intrinsic subtype (HER2-enriched, luminal, basal).

NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 will be utilized for AE reporting

Mean difference will be estimated between HP FDC SC and IV admin of HP in sub-study

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Antioxidant Supplements, Genetics and Chemotherapy Outcomes	NCT03413761	Node Positive B... Node Negative B...		18 Years -	Roswell Park Cancer Institute
A Single Arm Phase II Study of ADjuvant Endocrine Therapy, Pertuzumab, and Trastuzumab for Patients With Anatomic Stage I Hormone Receptor-positive, HER2-positive Breast Cancer	NCT04569747	HER2-positive B... Invasive Carcin... Breast Cancer Node Negative B... Micrometastasis... Hormone Recepto...	Pertuzumab+TRAS... ADJUVANT ENDOCR...	18 Years -	Dana-Farber Cancer Institute
Antioxidant Supplements, Genetics and Chemotherapy Outcomes	NCT03413761	Node Positive B... Node Negative B...		18 Years -	Roswell Park Cancer Institute

Spots Global Cancer Trial Database for node negative breast cancer