Molecular Testing and Imaging in Improving Response in Patients With Stage I-III Triple-Negative Breast Cancer Receiving Chemotherapy MDACC Breast Moonshot Initiative

NCT02276443 | Active Not Recruiting DMC

• 3 other identifiers: 2014-0185NCI-2015-00191P30CA016672
• Study Type: interventional
• Target: 798
• Locations: 1 country
• Sites: 5

Brief Summary

This clinical trial assesses whether a newly designed algorithm which looks at the genomic signature of each patient's tumor to predict their sensitivity to standard of care treatment verses being placed on a personally designed treatment trial can improve the responses in patients with newly diagnosed triple-negative breast cancer (TNBC). Testing the primary tumor biopsy for certain proteins and monitoring the lymphocyte infiltration into the tumors may help doctors determine the sub-type of TNBC, and direct treatments that may work well. It is not yet known whether assigning treatment based on the patient's tumor classification will improve how well the tumor responds.

Conditions

Invasive Breast Carcinoma; Stage I Breast Cancer AJCC v7; Stage IA Breast Cancer AJCC v7; Stage IB Breast Cancer AJCC v7; Stage II Breast Cancer AJCC v6 and v7; Stage IIA Breast Cancer AJCC v6 and v7; Stage IIB Breast Cancer AJCC v6 and v7; Stage III Breast Cancer AJCC v7; Stage IIIA Breast Cancer AJCC v7; Stage IIIB Breast Cancer AJCC v7; Stage IIIC Breast Cancer AJCC v7; Triple-Negative Breast Carcinoma

Outcome Measures

Primary Outcomes (1)

• Response rate

  A one-sided z-test will be used to compare the response rates of the treatment and control arms. The study will have 80% power to detect an increase in the response rate of 14.2 percentage points assuming a control arm response rate of 50% at the 0.05 significance level allowing for two interim tests for both futility and superiority.

  Up to 5 years

Secondary Outcomes (2)

• Survival

  Up to 5 years

• Frequency of tumors

  Up to 5 years

Study Arms (3)

Arm A (predictive results given)

EXPERIMENTAL

Patients undergo baseline molecular and IHC evaluation of their tumor biopsy, and receive the results. Patients then receive standard anthracycline-based chemotherapy and undergo standard ultrasound at baseline, after 2 cycles, after 4 cycles of treatment, and after completion of treatment (before surgery). Patients and physicians are notified of the results of the molecular evaluation. Patients may then choose to continue with standard taxane +/- platinum-based chemotherapy or participate in an experimental clinical trial designed to match the molecular profile and triple-negative subtype. Patients with tumors predicted to be insensitive to chemotherapy are advised to participate in a clinical trial treating their tumor subtype.

Drug: Chemotherapy; Other: Laboratory Biomarker Analysis; Procedure: Lymph Node Biopsy; Procedure: Ultrasonography

Arm B (predictive results given)

EXPERIMENTAL

Patients undergo baseline molecular and IHC evaluation of their tumor biopsy, and receive the results. Patients then receive standard anthracycline-based chemotherapy and undergo standard ultrasound at baseline, after 2 cycles, and after 4 cycles of treatment. Patients and physicians are notified of the results of the molecular evaluation. Patients may then choose to continue with standard taxane +/- platinum-based chemotherapy or participate in an experimental clinical trial designed to match the molecular profile and triple-negative subtype. Patients with tumors predicted to be insensitive to chemotherapy are advised to participate in a clinical trial treating their tumor subtype.

Drug: Chemotherapy; Other: Laboratory Biomarker Analysis; Procedure: Lymph Node Biopsy; Procedure: Ultrasonography

Arm C (predictive results given)

EXPERIMENTAL

Patients undergo baseline molecular and IHC evaluation of their tumor biopsy, and receive the results. Patients then receive standard anthracycline-based chemotherapy with immunotherapy and undergo standard ultrasound at baseline, after 2 cycles, and after 4 cycles of treatment. Patients and physicians are notified of the results of the molecular evaluation. Patients may then choose to continue with standard taxane +/- platinum-based chemotherapy or participate in an experimental clinical trial designed to match the molecular profile and triple-negative subtype. Patients with tumors predicted to be insensitive to chemotherapy are advised to participate in a clinical trial treating their tumor subtype

Drug: Chemotherapy; Other: Immunotherapy; Other: Laboratory Biomarker Analysis; Procedure: Lymph Node Biopsy; Procedure: Ultrasonography

Interventions

Chemotherapy DRUG

Receive standard chemotherapy

Also known as: Chemo, Chemotherapy (NOS), Chemotherapy, Cancer, General

Arm A (predictive results given); Arm B (predictive results given); Arm C (predictive results given)

Immunotherapy OTHER

Receive standard immunotherapy

Also known as: Immunological, Immunological Therapy, Immunologically Directed Therapy

Arm C (predictive results given)

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm A (predictive results given); Arm B (predictive results given); Arm C (predictive results given)

Lymph Node Biopsy PROCEDURE

Undergo baseline lymph node evaluation

Also known as: Biopsy of Lymph Node

Arm A (predictive results given); Arm B (predictive results given); Arm C (predictive results given)

Ultrasonography PROCEDURE

Undergo standard ultrasound

Also known as: 2-Dimensional Grayscale Ultrasound Imaging, 2-Dimensional Ultrasound Imaging, 2D-US, Ultrasound, Ultrasound Imaging, Ultrasound Test, Ultrasound, Medical, US

Arm A (predictive results given); Arm B (predictive results given); Arm C (predictive results given)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The patient can undergo biopsy or surgery of a primary tumor site for suspected or proven invasive breast cancer of clinical stage I to III and are planned to receive neoadjuvant therapy with anthracycline/taxane based regimens (Arm A and Arm B) or chemotherapy/immunotherapy-based regimens (Arm C)
• The patient was proven to have TNBC, defined from standard pathologic assays as negative for ER and PR (\< 10% tumor staining) and negative for HER2 (immunohistochemistry \[IHC\] score \< 3, gene copy number not amplified)
• Patients must have left ventricular ejection fraction (LVEF) \>= 50% by multi gated acquisition scan (MUGA) or echocardiogram (ECHO) within 12 weeks prior to starting adriamycin
• Leukocytes \> 3,000/mcL
• Absolute neutrophil count \> 1,500/mcL
• Platelets \> 100,000/mcL
• Total bilirubin =\< 1.5 x upper limit of normal (ULN)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) \< 2.5 x institutional upper limit of normal
• Creatinine within 1.5 X the upper limits of normal OR creatinine clearance \> 60 mL/min/1.73 m\^2 for patients with creatinine levels above institutional normal
• For Arms A and B, patients must be medically ineligible to receive immunotherapy in combination with anthracycline/taxane-based chemotherapy as part of standard care
• For Arm C, patients must be medically eligible to receive immunotherapy in combination with chemotherapy as part of standard of care

You may not qualify if:

• The patient has diagnosis of stage IV disease or is found to have stage IV disease prior to initiation of chemotherapy
• Prior history of invasive cancer within 5 years of study entry or history of metastatic cancer; exceptions include non-metastatic, curatively treated basal and squamous cell carcinoma of the skin
• Prior excisional biopsy of the primary invasive breast cancer
• Patients with hematomas or biopsy site changes that limit response assessment of the primary tumor by diagnostic imaging
• Patients not eligible for chemotherapy with taxane and/or anthracycline based chemotherapy regimens
• Prior therapy with - chemotherapy and/or immunotherapy
• Grade II or higher neuropathy
• Patients with Zubrod performance status of \> 2
• Patients with history of serious cardiac events defined as:
• Patients with a history of New York Heart Association class 3 or 4 heart failure, or history of myocardial infarction, unstable angina or cerebrovascular accident (CVA) within 6 months of protocol registration
• Patients who have history of PR prolongation (grade 2 or higher) or atrioventricular (AV) block

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (5)

MD Anderson in The Woodlands

Conroe, Texas, 77384, United States

Location

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MD Anderson West Houston

Houston, Texas, 77079, United States

Location

MD Anderson League City

League City, Texas, 77573, United States

Location

MD Anderson in Sugar Land

Sugar Land, Texas, 77478, United States

Location

Related Publications (8)

• Wang X, Zhao L, Song X, Wu X, Krishnamurthy S, Semba T, Shao S, Knafl M, Coffer LW 2nd, Alexander A, Vines A, Bopparaju S, Woodward WA, Chu R, Zhang J, Yam C, Loo LWM, Nasrazadani A, Huong LP, Woodman SE, Futreal A; Rare Tumor Initiative Team; Tripathy D, Ueno NT. Genomic and transcriptomic analyses identify distinctive features of triple-negative inflammatory breast cancer. NPJ Precis Oncol. 2024 Nov 18;8(1):265. doi: 10.1038/s41698-024-00729-0.

  PMID: 39558017 DERIVED

• Stowers CE, Wu C, Xu Z, Kumar S, Yam C, Son JB, Ma J, Tamir JI, Rauch GM, Yankeelov TE. Combining Biology-based and MRI Data-driven Modeling to Predict Response to Neoadjuvant Chemotherapy in Patients with Triple-Negative Breast Cancer. Radiol Artif Intell. 2025 Jan;7(1):e240124. doi: 10.1148/ryai.240124.

  PMID: 39503605 DERIVED

• Basho RK, Zhao L, White JB, Huo L, Bassett RL, Mittendorf EA, Thompson A, Litton JK, Ueno N, Arun B, Lim B, Valero V, Tripathy D, Zhang J, Adrada BE, Santiago L, Ravenberg E, Seth S, Yam C, Moulder SL, Damodaran S. Comprehensive Analysis Identifies Variability in PI3K Pathway Alterations in Triple-Negative Breast Cancer Subtypes. JCO Precis Oncol. 2024 Mar;8:e2300124. doi: 10.1200/PO.23.00124.

  PMID: 38484209 DERIVED

• Chen H, Ding Q, Khazai L, Zhao L, Damodaran S, Litton JK, Rauch GM, Yam C, Chang JT, Seth S, Lim B, Thompson AM, Mittendorf EA, Adrada B, Virani K, White JB, Ravenberg E, Song X, Candelaria R, Arun B, Ueno NT, Santiago L, Saleem S, Abouharb S, Murthy RK, Ibrahim N, Routbort MJ, Sahin A, Valero V, Symmans WF, Tripathy D, Wang WL, Moulder S, Huo L. PTEN in triple-negative breast carcinoma: protein expression and genomic alteration in pretreatment and posttreatment specimens. Ther Adv Med Oncol. 2023 Aug 2;15:17588359231189422. doi: 10.1177/17588359231189422. eCollection 2023.

  PMID: 37547448 DERIVED

• Hwang KP, Elshafeey NA, Kotrotsou A, Chen H, Son JB, Boge M, Mohamed RM, Abdelhafez AH, Adrada BE, Panthi B, Sun J, Musall BC, Zhang S, Candelaria RP, White JB, Ravenberg EE, Tripathy D, Yam C, Litton JK, Huo L, Thompson AM, Wei P, Yang WT, Pagel MD, Ma J, Rauch GM. A Radiomics Model Based on Synthetic MRI Acquisition for Predicting Neoadjuvant Systemic Treatment Response in Triple-Negative Breast Cancer. Radiol Imaging Cancer. 2023 Jul;5(4):e230009. doi: 10.1148/rycan.230009.

  PMID: 37505106 DERIVED

• Wu C, Jarrett AM, Zhou Z, Elshafeey N, Adrada BE, Candelaria RP, Mohamed RMM, Boge M, Huo L, White JB, Tripathy D, Valero V, Litton JK, Yam C, Son JB, Ma J, Rauch GM, Yankeelov TE. MRI-Based Digital Models Forecast Patient-Specific Treatment Responses to Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer. Cancer Res. 2022 Sep 16;82(18):3394-3404. doi: 10.1158/0008-5472.CAN-22-1329.

  PMID: 35914239 DERIVED

• Yam C, Abuhadra N, Sun R, Adrada BE, Ding QQ, White JB, Ravenberg EE, Clayborn AR, Valero V, Tripathy D, Damodaran S, Arun BK, Litton JK, Ueno NT, Murthy RK, Lim B, Baez L, Li X, Buzdar AU, Hortobagyi GN, Thompson AM, Mittendorf EA, Rauch GM, Candelaria RP, Huo L, Moulder SL, Chang JT. Molecular Characterization and Prospective Evaluation of Pathologic Response and Outcomes with Neoadjuvant Therapy in Metaplastic Triple-Negative Breast Cancer. Clin Cancer Res. 2022 Jul 1;28(13):2878-2889. doi: 10.1158/1078-0432.CCR-21-3100.

  PMID: 35507014 DERIVED

• Yam C, Yen EY, Chang JT, Bassett RL, Alatrash G, Garber H, Huo L, Yang F, Philips AV, Ding QQ, Lim B, Ueno NT, Kannan K, Sun X, Sun B, Parra Cuentas ER, Symmans WF, White JB, Ravenberg E, Seth S, Guerriero JL, Rauch GM, Damodaran S, Litton JK, Wargo JA, Hortobagyi GN, Futreal A, Wistuba II, Sun R, Moulder SL, Mittendorf EA. Immune Phenotype and Response to Neoadjuvant Therapy in Triple-Negative Breast Cancer. Clin Cancer Res. 2021 Oct 1;27(19):5365-5375. doi: 10.1158/1078-0432.CCR-21-0144.

  PMID: 34253579 DERIVED

MeSH Terms

Conditions

Breast Neoplasms; Triple Negative Breast Neoplasms

Interventions

Drug Therapy; Immunotherapy; Adjuvants, Immunologic; Sentinel Lymph Node Biopsy; High-Energy Shock Waves

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Therapeutics; Immunomodulation; Biological Therapy; Immunologic Factors; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Biopsy; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Lymph Node Excision; Investigative Techniques; Ultrasonic Waves; Sound; Radiation, Nonionizing; Radiation; Physical Phenomena

Study Officials

• Clinton Yam

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 21, 2014
• First Posted: October 28, 2014
• Study Start: November 9, 2015
• Primary Completion (Estimated): November 30, 2026
• Study Completion (Estimated): November 30, 2026
• Last Updated: August 1, 2025

Record last verified: 2025-07

Locations

US (5)