Functional Precision Oncology to Predict, Prevent, and Treat Early Metastatic Recurrence of TNBC

NCT05464082 | Recruiting Phase 2 DMC

• 1 other identifier: HCI153239
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

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/Her2 negative or triple negative breast cancer.

Conditions

Breast Cancer Recurrent

Outcome Measures

Primary Outcomes (3)

• Proportion of cases where clinically actionable therapies were identified by FPO.

  Assess the feasibility and utility of Functional Precision Oncology (FPO) testing to identify therapies for patients with TNBC or HR-low/HER2- breast cancer who are at high risk of early recurrence

  up to 3 years

• Compare the recurrence rates between patients whose tumors successfully engrafted in mice (PDX+) vs. not (PDX-)

  Confirm that tumor engraftment as a PDX predicts early metastatic recurrence

  Data will be assessed at 1-year from the time of definitive surgery.

• Compare the recurrence rates between patients whose tumors successfully engrafted in mice (PDX+) vs. not (PDX-)

  Confirm that tumor engraftment as a PDX predicts early metastatic recurrence

  Data will be assessed at 3-years from the time of definitive surgery.

Secondary Outcomes (7)

• Correlation between tumor engraftment (PDX+/-) and relapse-free survival, overall survival, and response to preoperative chemotherapy and treatment response as assessed on the Residual Cancer Burden scale

  up to 3 years

• Proportion of cases where any type of patient derived models are successfully generated and clinically actionable therapies are identified by functional precision oncology.

  up to 3 years

• Correlation between MHCII Immune Activation Score (high vs. low and as a continuous variable) and tumor engraftment (PDX+/-) and clinical outcomes (relapse-free and overall survival).

  up to 3 years

• Correlation between methylated ctDNA measurements as assessed using the MethylPatch assay pretreatment, pre- and post surgery, with PDX engraftment data (+/-) and clinical outcomes (relapse-free and overall survival)

  up to 3 years

• frequency with which therapeutic responses in PDX, PDxO, and/or PDO align with the clinical, radiographic, and pathologic responses observed in the matched patient

  up to 3 years

Study Arms (2)

Treatment: All Patients

EXPERIMENTAL

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".

Other: Functional Precision Oncology

Physician Questionnaire

NO 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.

Interventions

Functional Precision Oncology OTHER

Patient derived models (PDMs), comprising patient derived xenografts (PDXs) and organoids (PDO and PDxO),

Treatment: All Patients

Eligibility Criteria

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

You may qualify if:

• Subject aged ≥ 18 years.
• Subject has Stage I-III disease.
• Histologically or cytologically confirmed invasive breast carcinoma that is triple negative (TNBC) or hormone receptor (HR)-low/Her2 negative
• TNBC is defined as:
• HER2 expression 0 or 1+ on immunohistochemistry (IHC) or non-amplified (defined as HER2/CEP17 ratio \<2 or copy number \<6) on fluorescence in situ hybridization (FISH). If HER2 expression is 2+ on IHC, non-amplified HER2 expression must be confirmed by FISH. Pathologic diagnosis of TNBC (negative HER2 status by cytogenetics, \<1% of cells stained positive for estrogen receptor (ER) by IHC, and \<1% of cells stained positive for progesterone receptor (PR) by IHC).
• HR-low/Her2(-) is defined as:
• HER2 expression 0 or 1+ on IHC or non-amplified (defined as HER2/CEP17 ratio \<2 or copy number \<6) on fluorescence in situ hybridization (FISH). If HER2 expression is 2+ on IHC, non-amplified HER2 expression must be confirmed by FISH.1-10% of cells stained positive for ER by IHC, and/or 1-10% of cells stained positive for PR by IHC).
• Primary tumor OR local lymph node metastasis that is ≥ 1.5 cm. Patients with inflammatory breast cancer are eligible, regardless of tumor size. Patients with multifocal or multicentric breast cancer are eligible so long as ALL tumors biopsied per standard of care guidelines and/or investigator discretion meet receptor status criteria, and at least one tumor measures ≥ 1.5 cm.
• Patient is considered for preoperative cytotoxic chemotherapy per standard of care or in the context of a separate, ongoing clinical trial.
• Patient has not received any prior therapy for thier breast cancer.
• Willing and capable (per treating investigator's assessment) to undergo baseline tumor material collection from the primary tumor or lymph node metastasis.
• Patient can safely undergo tumor collection:
• The tumor is reasonably accessible to tumor collection
• The tumor is amenable to tumor collection (e.g. does not abut neurovascular structures)
• If the patient receives anticoagulation, anticoagulation can be safely withheld to accommodate for tumor material acquisition

You may not qualify if:

• Willing and able to answer the physician questionnaires at the protocol required time points.
• Willing and able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines.
• Evidence of metastatic breast cancer
• ER and/or PR expression \>10% on immunohistochemistry
• Her2(+) and/or Her2-amplified breast cancer. HER2 expression 3+ on IHC or amplified (defined as HER2/CEP17 ratio ≥2 or copy number \>6) on fluorescence in situ hybridization (FISH). If HER2 expression is 2+ on IHC, reflex FISH must be performed to determine eligibility.
• Patient has bilateral breast cancer
• Patient received any anti-cancer therapy or any investigational therapy prior to study entry and collection of tumor.
• Treatment includes: neoadjuvant therapy, radiation therapy, chemotherapy, bisphosphonates for an indication other than osteopenia/osteoporosis, and/or hormonal therapy administered for the currently diagnosed primary breast cancer prior to study entry. Hormonal therapy for a prior diagnosis of a hormone receptor-positive breast cancer us allowed.
• The diagnosis of another malignancy, unless the patient is considered disease-free for ≥5 years before study entry. Patients are eligible if diagnosed and treated for carcinoma in situ of the cervix, melanoma in situ, colon cancer in situ, ductal carcinoma in situ, and basal and/or squamous cell carcinoma of the skin, early stage papillary thyroid cancer, and other low risk malignancies per investigator discretion.
• The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
• Myocardial infarction (\<6 months prior to enrollment), unstable angina, congestive heart failure (\> New York Heart Association Classification Class IIB) or a serious cardiac arrhythmia requiring medication.
• Renal or liver disease that prohibits the patient from receiving at least single-agent full recommended dose chemotherapy.
• Current evidence of uncontrolled, significant intercurrent illness including, but not limited to, the following conditions:
• Cardiovascular disorders:
• Congestive heart failure New York Heart Association Class III or IV, unstable angina pectoris, serious cardiac arrhythmias.

Sponsors & Collaborators

• University of Utah: lead
• United States Department of Defense: collaborator

Study Sites (1)

Huntsman Cancer Institute at University of Utah

Salt Lake City, Utah, 84112, United States

RECRUITING

Study Officials

• Christos Vaklavas, MD

  Huntsman Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Janna Espinosa

CONTACT

801-585-0571; janna.espinosa@hci.utah.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 15, 2022
• First Posted: July 19, 2022
• Study Start: January 6, 2023
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): September 30, 2028
• Last Updated: February 20, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)