Functional Precision Oncology for Breast Cancer Recurrence

(TOWARDS-II Trial)

Overseen By Janna Espinosa

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Utah

Must not be taking: Anticancer, Investigational, Chemotherapy, others

Disqualifiers: Metastatic cancer, Bilateral cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new approach called Functional Precision Oncology to predict, prevent, and treat early metastatic recurrence in certain types of breast cancer, specifically HR-low/Her2 negative or triple-negative breast cancer. Researchers grow samples from patients' tumors in a lab to observe their response to different drugs, aiding doctors in selecting the most effective treatments. Suitable participants include those with triple-negative or HR-low/Her2 negative breast cancer that is at least 1.5 cm in size and who are considering chemotherapy before surgery. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering a chance to contribute to significant advancements in breast cancer care.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, it mentions that patients should not have received any prior therapy for their breast cancer before joining the study.

Is there any evidence suggesting that Functional Precision Oncology is likely to be safe for humans?

Research has shown that Functional Precision Oncology (FPO) is generally well-tolerated in studies. FPO uses samples from a patient's tumor to test various drugs, identifying the best treatment for each individual. This personalized approach helps doctors select treatments that are more effective and less likely to cause serious side effects.

In earlier studies, serious side effects were rare. Most patients experienced mild to moderate side effects, which are common with many cancer treatments. The study's later phase indicates that previous research demonstrated a reasonable level of safety for the treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about Functional Precision Oncology (FPO) for breast cancer recurrence because it personalizes treatment by using patient-derived tumor models to test drug responses. Unlike standard options like chemotherapy and hormone therapy, FPO involves growing patient tumors in mice and developing organoids to predict which drug combinations might work best for an individual. This method not only tailors therapy but also provides detailed insights into tumor behavior and potential resistance, offering a more informed approach to selecting second-line treatments when the first-line options no longer work.

What evidence suggests that Functional Precision Oncology could be effective for breast cancer recurrence?

Research has shown that Functional Precision Oncology (FPO) can manage breast cancer by customizing treatments for each patient. Early results indicated a 59% success rate in shrinking or eliminating tumors in other cancer types. In this trial, all patients will undergo FPO, which tests tumor samples with various drugs to identify the most effective treatment. This approach aims to prevent early cancer recurrence and improve patient outcomes. For breast cancer, particularly challenging types like triple-negative, FPO could offer a more personalized and effective treatment option. ^{1 2 3 6 7}

Who Is on the Research Team?

Christos Vaklavas

Principal Investigator

Huntsman Cancer Institute

Are You a Good Fit for This Trial?

This trial is for adults with invasive breast cancer that's triple negative or HR-low/Her2 negative, who haven't had prior therapy. They must be able to provide a biopsy sample and consent, have an ECOG Performance Status ≤ 2, and a life expectancy of ≥ 12 months. Excluded are those with Her2(+) cancer, other malignancies within the last 5 years, severe heart conditions, uncontrolled hypertension, or any condition affecting study compliance.

Inclusion Criteria

Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines

My breast cancer is triple negative or has low hormone receptors and is HER2 negative.

Life expectancy of ≥ 12 months as assessed by the treating investigator

Exclusion Criteria

I don't have recent severe illnesses like heart attack or liver disease that would prevent me from receiving standard chemotherapy.

My breast cancer has spread to other parts of my body.

I have been cancer-free from another type of cancer for over 5 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Preoperative Treatment

Participants undergo preoperative chemotherapy, surgery, and radiation while PDX and organoid models are developed for drug profiling.

12-24 weeks

Disease-Free Interval

PDX and organoid establishment and drug profiling may extend into this phase.

Variable

Metastatic Treatment

Participants receive first line therapy in the metastatic setting per SOC or in separate clinical trial. Results of PDM drug profiling, tumor genomic, and circulating tumor DNA results will be returned to treating physician to inform 2nd line therapy.

Up to 3 years

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of progression-free survival and overall survival.

Up to 3 years

What Are the Treatments Tested in This Trial?

Interventions

• Functional Precision Oncology

Trial Overview

The trial tests Functional Precision Oncology (FPO) to predict and manage early metastatic recurrence in certain breast cancers. It involves collecting tumor samples before any treatment starts to develop personalized models like PDX or organoids for each patient.

How Is the Trial Designed?

Group I: Treatment: All Patients Experimental Treatment 1 Intervention

Patient derived xenografts (PDX) are grown in mice. Organoids may generated from patient tumor(PDO) and PDX(PDxO). Organoids will be used for drug profiling. PDX, organoid establishment and drug profiling will occur while patient is undergoing preoperative chemo, surgery, radiation, and may extend into disease-free interval. Patients receive first line therapy in the metastatic setting per SOC or in separate clinical trial. Results of PDM drug profiling, tumor genomic, and circulating tumor DNA results will be returned to treating physician to inform 2nd line therapy. At progression on the first line therapy, the patient will begin new therapy as directed by the treating physician. Any subsequent therapy (aligned or unaligned with report recommendations) that a patient starts after the return of results will be deemed "informed".

Group II: Physician Questionnaire Active Control 1 Intervention

Prior to the return of results, treating physicians will be asked to complete the PRE-Information Provider Survey on Functional Precision Oncology. After review of the FPO results, treating physicians will be asked to complete the POST-Information Provider Survey on Functional Precision Oncology to assess the potential effect that the FPO results have on the selection of therapy. These surveys will be administered to assess the impact the results have on the selection of therapy. Physicians are not mandated to select the treatment recommended by the FPO data since the FPO results are not from a CLIA certified laboratory. Information regarding whether the physician chose to switch to the recommended drug or not for the next line of therapy and patient outcomes (progression-free survival) according to treatment selection (treatment selected aligned with FPO recommendation vs. not) will be captured.

Who Is Running the Clinical Trial?

University of Utah

Lead Sponsor

Trials

1,169

Recruited

1,623,000+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Published Research Related to This Trial

Functional genomic studies in breast cancer have identified specific genes that influence how patients respond to endocrine therapies, which can vary based on genetic differences and the type of drug used.

These insights from clinical trials highlight the potential for personalized medicine approaches in breast cancer treatment, allowing for more tailored and effective therapeutic strategies based on individual genetic profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Functional genomics based on germline genome-wide association studies of endocrine therapy for breast cancer. Zayas, J., Qin, S., Yu, J., et al.[2021]

Precision medicine in cancer treatment is advancing with targeted therapies and companion diagnostic tests that help identify patients who will benefit most, although large-scale randomized trials are still needed to confirm their effectiveness.

Melanoma serves as a key example of how understanding molecular drivers can lead to effective targeted therapies and immune system activation, paving the way for future treatments that are highly specific and less toxic.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Precision cancer medicine: the future is now, only better. Tsimberidou, AM., Eggermont, AM., Schilsky, RL.[2022]

In a study of 1,000 patients who underwent FoundationOne CDx™ testing, 652 had actionable mutations, and 38 received targeted therapies, showing a disease control rate of 41.2% with some patients achieving partial responses.

The median progression-free survival was 2.7 months and median overall survival was 9.9 months, indicating that while targeted therapies based on genetic alterations can be beneficial, further research is needed to fully understand their efficacy in community oncology settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of Precision Medicine on Clinical Outcomes: A Single-Institution Retrospective Study. Quinn, R., Patel, R., Sison, C., et al.[2023]

The study introduces DBPOM, a comprehensive web server that integrates drug efficacy and toxicity data for over 10,000 small molecule compounds, aiding in cancer precision medicine by allowing clinicians to analyze both the positive and negative effects of drugs on patients.

By bridging the gap between cell culture and living tissue, the platform helps predict the effectiveness of FDA-recommended drugs based on individual genetic characteristics, making it a valuable resource for personalized cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comprehensive tool for tumor precision medicine with pharmaco-omics data analysis. Liu, Y., Song, F., Li, Z., et al.[2023]

A functional precision oncology (fPO) strategy using patient-derived ovarian cancer cells (PDCs) revealed that low-grade serous ovarian cancers (LGSOCs) respond better to targeted inhibitors compared to high-grade serous ovarian cancers (HGSOCs), indicating potential for tailored treatments.

In a clinical case study, fPO-guided therapy for a patient with metastatic LGSOC led to significant tumor reduction and disease control over five years, demonstrating the effectiveness of personalized treatment approaches in ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug response profiles in patient-derived cancer cells across histological subtypes of ovarian cancer: real-time therapy tailoring for a patient with low-grade serous carcinoma. Murumägi, A., Ungureanu, D., Khan, S., et al.[2023]

Functional assays that assess how cancer cells respond to drugs can help personalize cancer treatment, providing valuable insights that traditional diagnostic tests may not offer.

These assays have shown promising clinical results and are moving towards routine clinical use, but challenges remain in improving their accuracy and integrating them with existing diagnostic methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Benefits of functional assays in personalized cancer medicine: more than just a proof-of-concept. Morand du Puch, CB., Vanderstraete, M., Giraud, S., et al.[2022]

Functional precision medicine offers a promising approach to cancer treatment by using drug sensitivity screening on living tumor cells, which can provide more personalized treatment options than traditional genomic methods.

Current genomic strategies only help a small number of patients, while integrating artificial intelligence with functional precision medicine could enhance patient stratification and improve treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Functional precision cancer medicine: drug sensitivity screening enabled by cell culture models. Flobak, Å., Skånland, SS., Hovig, E., et al.[2022]

In a study involving 736 breast cancer patients from the I-SPY 2 Trial, researchers identified specific protein biomarkers, such as elevated levels of cyclin D1 and estrogen receptor alpha, that are associated with resistance to treatment, helping to predict which patients may not respond to therapy.

The study introduced a new predictive signature based on HER2 activation that can help stratify triple-negative breast cancer patients for targeted therapies, demonstrating how protein activation signatures can enhance treatment selection alongside traditional gene expression profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protein signaling and drug target activation signatures to guide therapy prioritization: Therapeutic resistance and sensitivity in the I-SPY 2 Trial. Gallagher, RI., Wulfkuhle, J., Wolf, DM., et al.[2023]

Functional precision medicine uses live tumor cells from patients to test drug responses directly, offering personalized insights that could lead to better treatment decisions compared to traditional methods that rely on static tumor features.

This approach addresses the limitations of static analyses, which often fail to benefit a significant number of patients, by identifying specific vulnerabilities in tumors that can be targeted for therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Functional precision oncology: Testing tumors with drugs to identify vulnerabilities and novel combinations. Letai, A., Bhola, P., Welm, AL.[2023]

A 95-gene signature was identified that effectively stratifies hormone receptor-positive early breast cancer patients into high-risk and low-risk groups, significantly predicting distant relapse-free survival (DRFS) with a hazard ratio of 5.05, based on analysis of 3825 patients from the TEAM trial.

This prognostic signature not only outperformed existing multiparametric tests but also remained predictive for patients who received adjuvant chemotherapy, highlighting its potential to guide treatment decisions and prioritize patients for targeted therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular stratification of early breast cancer identifies drug targets to drive stratified medicine. Bayani, J., Yao, CQ., Quintayo, MA., et al.[2020]

The ADEStrata approach, developed in this study, allows for the stratification of tumor mutations based on adverse drug events (ADEs), specifically focusing on musculoskeletal adverse events in breast cancer patients treated with aromatase inhibitors, using data from 212 patients.

By prioritizing somatic variants linked to ADEs, the study found that this method can identify high-risk patients who may experience poor outcomes, suggesting that it could help tailor cancer therapies to improve patient safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Drug Event-based Stratification of Tumor Mutations: A Case Study of Breast Cancer Patients Receiving Aromatase Inhibitors. Wang, C., Zimmermann, MT., Prodduturi, N., et al.[2018]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05464082

NCT05464082 | Functional Precision Oncology to Predict, ...

This is a prospective phase 2 study to use Functional Precision Oncology (FPO) to predict, prevent and treat early metastatic recurrence in subjects with HR-low ...

2.

cancer.gov

cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2022-08187

Functional Precision Oncology to Predict, Prevent, and ...

This phase II trial tests functional precision oncology to predict, prevent, and treat patients with stage I-III triple negative breast cancer and hormone ...

3.

sciencedirect.com

sciencedirect.com/science/article/pii/S147149142400282X

Functional precision medicine: the future of cancer care

Functional precision oncology to predict, prevent, and treat early metastatic recurrence of TNBC, Recurrent breast cancer, Adults, 80, NCT05464082, UT, USA.

4.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8752507/

Functional precision oncology: testing tumors with drugs to ...

They observed a 59% objective response rate, with 45% receiving a complete remission of the leukemia (with or without complete hematologic recovery). The ...

5.

aacrjournals.org

aacrjournals.org/cancerres/article/85/5_Supplement/B028/751846/Abstract-B028-Functional-precision-medicine-in

Functional precision medicine in challenging breast cancer ...

FPM enables a more tailored and potentially effective treatment strategy, particularly for complex cancers such as invasive breast carcinoma, ...

6.

trialx.com

trialx.com/clinical-trials/listings/272370/functional-precision-oncology-for-metastatic-breast-cancer/

Functional Precision Oncology for Metastatic Breast Cancer

The trial will seek to provide personalized genomic and drug sensitivity information to eligible patients with metastatic breast cancer prior to ...

7.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12032834/

The treatment of breast cancer in the era of precision medicine

The risk of distant recurrence among patients with EBC diagnosed after the year 2000 was approximately 20% lower than the risk of those ...