Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Antirheumatic Agents

Anti-Infective Agents

Paclitaxel

Cyclophosphamide

Bevacizumab

Doxorubicin

Liposomal doxorubicin

Fluorouracil

Albumin-Bound Paclitaxel

Estrogens

Epirubicin

Tubulin Modulators

Antimitotic Agents

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Antimetabolites

Participants with Estrogen Receptor (ER)-Positive breast cancers receive Standard T/FAC or T/FEC chemotherapy before surgery.

T/FAC or T/FEC: Combination chemotherapy with sequential paclitaxel (80 mg/m2) weekly x 12 weeks followed by 5-fluorouracil (500 mg/m2), cyclophosphamide (500 mg/m2) and doxorubicin (50 mg/m2) or epirubicin (100 mg/m2) (FAC or FEC) once every 3 weeks for 4 treatments.

Participants with ER-negative cancers (randomized between Group 2 \& Group 3), Standard T/FAC or T/FEC chemotherapy before surgery.

Participants with ER-negative cancers (randomized between Group 2 \& Group 3), T/FEC chemotherapy combined with 10 mg Bevacizumab every 2 weeks during first 3 treatments before surgery.

80 mg/m2 by vein over about 1-2 hours once every 7 days x 12 courses.

500 mg/m2 for 4 courses (once every 7 days)

50 mg/m2 by vein given on day 1 and repeated once every 21 days for 4 treatments

100 mg/m2 by vein given on day 1 and repeated once every 21 days for 4 treatments, may be given instead of Doxorubicin in Group 1 and 2.

500 mg/m2 by vein given on day 1 and repeated once every 21 days for 4 treatments.

10 mg/kg intravenously every 2 weeks, discontinued 6 weeks before surgery (i.e. after 3rd course of FEC or FAC)

Lajos Pusztai, MD, DPHIL

The goal of this clinical research study is to learn if using "gene signatures" can be an effective way to decide the best treatment for breast cancer patients. Gene signatures may be able to help researchers predict who will respond to chemotherapy given before surgery.

At this time, treatment of stage I-III breast cancer for patients who are at high risk for the cancer returning is surgery and chemotherapy. If the cancer is positive for estrogen hormone receptor, patients also have endocrine therapy.

The most common standard chemotherapy treatment regimens for breast cancer at M. D. Anderson are paclitaxel (T), followed by treatments with fluorouracil (F), doxorubicin (A) or epirubicin (E), and cyclophosphamide (C). These chemotherapy combinations are known as T/FAC and T/FEC. However, not all patients respond to these treatments, so researchers at M. D. Anderson have developed tests to predict how much a person's breast cancer might respond to T/FAC or T/FEC chemotherapy.

Fine needle aspiration (FNA) of the tumor are collected after numbing the skin of the breast with local anesthesia, and the genes within the FNA sample are measured to calculate the results of treatment prediction tests before treatment is selected.

In this research study, the gene-based tests will help to select treatment based on the predictions of response to chemotherapy, and to then measure the tumor response from the surgery after the treatment.

Study Drugs:

T/FAC and T/FEC are designed to damage the DNA (genetic material of cells), which may cause cancer cells to die.

Bevacizumab is designed to block the growth of blood vessels that supply nutrients necessary for tumor growth. This may prevent or slow down the growth of cancer cells and make them more susceptible to chemotherapy.

Tumor Biopsies:

If you are found eligible to take part in this study, you will have 3-4 fine needle biopsies of the tumor collected. The skin over the tumor and the breast tissues surrounding the tumor will be numbed using local anesthesia. To perform fine needle aspiration biopsies, tumor cells are withdrawn from the tumor using a very thin needle alone, or using a syringe.

These biopsies will be used to measure different genes and to predict how the cancer may respond to different treatments.

Based on the information from these gene measurements, a computer model will predict if the cancer is highly sensitive to chemotherapy and is likely to shrink to a great extent or disappear completely due to chemotherapy. This response prediction is done separately for estrogen receptor-positive and estrogen receptor-negative cancers.

Study Groups:

If the biopsies show that the cancer may respond well to standard T/FAC or T/FEC chemotherapy, you will receive the chemotherapy before surgery (Group 1).

If the biopsies show that the cancer may not respond as well to standard T/FAC or T/FEC chemotherapy, you will be randomly assigned (as in the roll of dice) to 1 of 2 groups.

* If you are in Group 2, you will receive T/FAC or T/FEC chemotherapy before surgery. One (1) out of 3 participants whose cancer may not respond as well will be assigned to this group.
* If you are in Group 3, you will receive T/FAC or T/FEC chemotherapy combined with bevacizumab before surgery. Two (2) out of 3 participants whose cancer may not respond as well will be assigned to this group.

Your doctor will decide if you receive T/FAC or T/FEC.

Study Drug Administration:

Groups 1 and 2:

Once a week during Weeks 1-12, you will receive paclitaxel by vein over about 1-2 hours.

Once every 3 weeks during Weeks 13-24, you will receive T/FAC or T/FEC by vein over about 3-4 hours. This chemotherapy treatment is considered routine standard of care and you may receive this treatment closer to home outside of M. D. Anderson.

After all chemotherapy, you will have surgery at M. D. Anderson to remove the cancer.

Group 3:

Once a week during Weeks 1-12, you will receive paclitaxel by vein over about 1-2 hours.

Once every 2 weeks during Weeks 1-18, you will receive bevacizumab by vein once over about 1-2 hours. If your doctor thinks is it necessary, and based on heart related test results, you may only receive bevacizumab during Weeks 1-12.

Once every 3 weeks during Weeks 13-24, you will receive T/FAC or T/FEC by vein over about 4 hours. You must receive your chemotherapy at M. D. Anderson if you are in this group.

After all chemotherapy, you will have surgery at M. D. Anderson to remove the cancer.

Study Visits:

All participants will have routine visits at M. D. Anderson at least once every 12 weeks during chemotherapy. Your doctor will determine the tests and procedures to be performed.

If you are assigned to Group 3, you will also have the following additional procedures.

* You will have a urine analysis within 1 month after starting therapy.
* You will have an echocardiogram to check your heart's health within 3 months after you begin treatment.

Length of Study:

You may receive chemotherapy for up to 6 months. Once surgery is performed, your participation in this study is complete. Your doctor will decide together with you what further treatment you will need after surgery.

This is an investigational study. The biopsy and testing to predict response to chemotherapy is not FDA approved or commercially available. Its use in this study is investigational. The chemotherapy and surgery are standard of care for patients with breast cancer. The addition of bevacizumab to treatment is also investigational.

Up to 303 patients will take part in this study. All will be enrolled at M. D. Anderson.

Molecular Triaging of Newly Diagnosed Breast Cancer

Molecular Triaging of Newly Diagnosed Breast Cancer for Preoperative Therapies

Response is defined as pathologic complete (pCR/RCB-0) or near complete (RCB-I) response pathologic finding after completion of chemotherapy.

M.D. Anderson Cancer Center

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Carcinoma

Urinary Bladder Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Urinary Bladder Diseases

Urologic Diseases

Male Urogenital Diseases

Dermatologic Agents

Reproductive Control Agents

Gemcitabine

Methotrexate

Cisplatin

Vinblastine

Participants who are deemed eligible for cisplatin-based NAC will undergo:

* Standard of care neoadjuvant systemic therapy (currently cisplatin-based chemotherapy in cisplatin-eligible participants)
* Partial cystectomy with extended pelvic lymph node dissection
* Standard of care adjuvant systemic therapy in eligible patients

Participants who are deemed ineligible for cisplatin-based NAC will undergo:

* Partial cystectomy with extended pelvic lymph node dissection
* Standard of care adjuvant systemic therapy in eligible participants

Standard of care neoadjuvant systemic therapy is currently cisplatin-based chemotherapy in cisplatin-eligible participants. Participants will start treatment within 60 days of Transurethral Resection of Bladder Tumor. Regimens may include:

* Cisplatin - Gemcitabine (Gem/Cis)
* Dose Dense Methotrexate - Vinblastine - Adriamycin - Cisplatin (MVAC)

Neoadjuvant Chemotherapy

Partial cystectomy will then be performed using the surgical technique at the discretion of the treating Urologic Oncologist. Extended pelvic lymphadenectomy will then be performed at the discretion of the treating Urologic Oncologist. Surgery will be performed within 60 days of Transurethral Resection of Bladder Tumor for Cisplatin-ineligible participants. Surgery will be performed within 60 days of completing neoadjuvant chemotherapy for Cisplatin-eligible participants.

Partial cystectomy with Extended pelvic lymph node dissection

Standard of care adjuvant systemic therapy in eligible participants. The choice of adjuvant systemic therapy will be left to the discretion of the treating Medical Oncologist but must fall within the SOC as outlined in NCCN guidelines.

Adjuvant systemic therapy

Nima Almassi, MD

The goal of this clinical trial is to determine if a partial cystectomy with extended pelvic lymph node removal will be effective at treating Muscle-Invasive Bladder Cancer instead of a complete cystectomy with extended pelvic lymph node removal. This clinical trial aims to determine the safety and oncologic efficacy of the intervention, and to examine patient-reported quality of life outcomes in participants. Participants will receive the standard pre-surgery treatment for approximately 4 to 6 weeks. After the pre-surgery treatment is completed, participants will undergo a partial cystectomy with extended pelvic lymph node dissection. After surgery, participants will receive adjuvant systemic therapy.

Radical cystectomy (surgical removal of the bladder) with pelvic lymph node dissection and urinary diversion, with neoadjuvant chemotherapy in eligible participants, is the standard of care in participants with muscle-invasive bladder cancer (MIBC). While this has demonstrated efficacy in the treatment of MIBC, it has risk of perioperative morbidity and impacts quality of life. Partial cystectomy (surgical removal of a portion of the bladder) is one option for bladder-sparing treatment of select bladder cancer participants and is included in the National Comprehensive Cancer Network bladder cancer treatment guidelines. This treatment has the advantage of less invasive treatment with a lower risk of surgical complication and better health-related quality of life (HRQOL) while providing pathologic staging, however there are limited data on outcomes with this treatment, especially patient-reported HRQOL outcomes. Additionally, much of the existing literature on efficacy of this treatment predates the use of advanced imaging in preoperative staging and advances in surgical technique including use of minimally-invasive surgical approaches and enhanced-recovery post-operative care paths. Given these limitations in the existing literature, the aim of this clinical trial is to examine the safety and efficacy and HRQOL outcomes of partial cystectomy with extended pelvic lymph node dissection, with standard of care perioperative systemic therapy in eligible participants.

This is a single-center, prospective, phase II trial.

Partial Cystectomy & Extended Pelvic Lymph Node Dissection With SOC Perioperative Systemic Therapy

Phase II Trial on the Safety and Efficacy of Partial Cystectomy and Extended Pelvic Lymph Node Dissection With Standard of Care Perioperative Systemic Therapy in the Management of Muscle-Invasive Bladder Cancer (PRESERVE Trial)

Recurrence-Free Survival (RFS) is defined as the time from post-surgery baseline scan (revealing no recurrent/metastatic disease) until the first occurrence of either local or distant recurrence as assessed by CT or MRI and/or biopsy. The primary outcome of distant RFS will be assessed via Kaplan-Meier analysis

The Clavien-Dindo classification will measure post-operative complications. The Clavien-Dindo Classification of Post-operative Complications is a tool to assess complications following surgical treatment. This tool ranks complications on a scale of seven levels, with level 1 being the least complicated and 7 being the worst complication resulting in death. The average classification at 90 days will be assessed and reported.

The median duration of bladder recurrence-free survival at 2 years.

The median duration of muscle-invasive bladder recurrence-free survival at 2 years.

The median duration of bladder-intact survival at 2 years.

The median duration of cancer-specific survival at 2 years.

The mean changes in Genitourinary-specific HRQoL will be reported. The HRQoL survey is composed of five functional scales (physical, role, emotional, cognitive, and social functioning), three symptom scales (fatigue, nausea and vomiting, pain), a global health status/QoL, and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The scales and single-item measures range from 0 - 100, with higher values representing a higher response level.

Case Comprehensive Cancer Center

Hormones

Hormone Antagonists

After sentinel lymph node biopsy, surgery for standard axillary lymph node dissection. Pathological evaluation (include intraoperative pathological examination) is performed routinely. All women were to receive whole-breast opposing tangential-field radiation therapy. Adjuvant systemic therapy was determined by the treating physician.

After sentinel lymph node biopsy, no surgery of axillary lymph node In this study, the absence of surgery is the experimental arm (non-inferiority trial). Pathological evaluation (include intraoperative pathological examination) is performed routinely. All women were to receive whole-breast opposing tangential-field radiation therapy. Adjuvant systemic therapy was determined by the treating physician.

Sentinel lymph nodes are identified with the combining use of intraoperative gamma detector and/or blue dye.

Sentinel Lymph Node Biopsy

touch imprint cytology and/or frozen section and/or OSNA

Intraoperative Pathological Examination

Axillary lymph node dissection involving removal of at least level I and II nodes.

Axillary Lymph Node Dissection

Pathological Evaluation

Adjuvant systemic therapy was determined by the treating physician according to the recently NCCN.

Adjuvant Systemic Therapy

Whole-breast opposing tangential-field radiation therapy.

Radiation Therapy

Yong-sheng Wang, MD

Tao Ouyang, MD

Jiong Wu, MD

Feng-xi Su, MD

Hong-yuan Li, MD

The recently randomized trial (ASCOG Z0011) support that among patients with limited sentinel lymph node (SLN) metastatic breast cancer treated with breast conservation and systemic therapy, the use of sentinel lymph node biopsy (SLNB) alone compared with axillary lymph node dissection (ALND) did not result in inferior survival. These patients, therefore, are unlikely to benefit from further surgery that results in a longer period of hospitalization, higher costs and higher postoperative morbidity. This result has been written in the 2012 National Comprehensive Cancer Network Clinical Practice Guidelines.

However, Limitations of Z0011, such as failure to achieve target accrual and possible randomization imbalance favoring the SLNB-alone group, must be considered. In the other hand, further testing in different country are needed.

The investigators design and begin a prospective randomized multicenter phase III study of ALND vs. no ALND in breast Cancer with positive SLN--the validation of Z0011 in China.

OBJECTIVES:

To determine the effects of complete axillary lymph node dissection (ALND) on survival of patients with sentinel lymph node (SLN) metastasis of breast cancer.

OUTLINE: This is a randomized multicenter study. Before randomization, all women were stratified according to age (≤50 years, \>50 years), tumor size(≤2cm, \>2cm) and research center. All the patients underwent lumpectomy and sentinel lymph node biopsy (SLNB). Eligible women were randomly assigned to ALND or no ALND Active Comparator: Patients undergo axillary lymph node dissection involving removal of at least level I and II nodes.

Experimental: No surgery of axillary lymph node in this arm. All the patients were to receive whole-breast opposing tangential-field radiation therapy. The use of adjuvant systemic therapy was determined by the treating physician according to the recently NCCN.

Patients are followed up every 4 months for the first 2 years, every 6 months from the third year to the fifth year, and then annually for a total of 10 years.

Axillary Lymph Node Dissection Versus no Dissection in Breast Cancer With Positive Sentinel Lymph Node

A Prospective Randomized Multicenter Phase III Study of Axillary Lymph Node Dissection Versus no Dissection in Breast Cancer With Positive Sentinel Lymph Node--the Validation of Z0011 in China

Time from randomization to relapse or death.

Time from randomization to date of death.

Estimate the incidence of axillary recurrence after surgery followed by axillary dissection or after surgery alone.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Molecular Triaging of Newly Diagnosed Breast Cancer	NCT01159236	Breast Cancer	Paclitaxel Fluorouracil Doxorubicin Epirubicin Cyclophosphamid... Bevacizumab	18 Years -	M.D. Anderson Cancer Center
Partial Cystectomy & Extended Pelvic Lymph Node Dissection With SOC Perioperative Systemic Therapy	NCT06290687	Malignant Neopl... Muscle Invasive...	Neoadjuvant Che... Partial cystect... Adjuvant system...	19 Years -	Case Comprehensive Cancer Center
Axillary Lymph Node Dissection Versus no Dissection in Breast Cancer With Positive Sentinel Lymph Node	NCT01796444	Breast Cancer	Sentinel Lymph ... Intraoperative ... Axillary Lymph ... Pathological Ev... Adjuvant System... Radiation Thera...	18 Years - 70 Years	Shandong Cancer Hospital and Institute
Molecular Triaging of Newly Diagnosed Breast Cancer	NCT01159236	Breast Cancer	Paclitaxel Fluorouracil Doxorubicin Epirubicin Cyclophosphamid... Bevacizumab	18 Years -	M.D. Anderson Cancer Center
Axillary Lymph Node Dissection Versus no Dissection in Breast Cancer With Positive Sentinel Lymph Node	NCT01796444	Breast Cancer	Sentinel Lymph ... Intraoperative ... Axillary Lymph ... Pathological Ev... Adjuvant System... Radiation Thera...	18 Years - 70 Years	Shandong Cancer Hospital and Institute

Spots Global Cancer Trial Database for adjuvant systemic therapy