SRG-514 for Breast Cancer

Recruiting at 8 trial locations

Overseen By Kayti Aviano

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: SURGE Therapeutics

Must not be taking: NSAIDs

Disqualifiers: Inflammatory breast cancer, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 14 days

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the optimal dose of a new treatment, SRG-514, for patients undergoing breast cancer surgery. This marks the first human test of SRG-514, administered during surgery to evaluate its effectiveness and establish dosing for future studies. The trial seeks participants diagnosed with breast cancer or ductal carcinoma in situ (a type of early breast cancer) who plan to undergo breast-conserving surgery. As a Phase 1 trial, this research focuses on understanding SRG-514's effects in humans, offering participants the opportunity to be among the first to receive this new treatment.

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

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that SRG-514, also known as saracatinib, has been tested for safety in people with advanced solid tumors. Most participants tolerated it well, experiencing no serious side effects. This suggests the treatment could be safe for humans, but it remains under study in this trial.

As a Phase 1 trial, this stage is early in the testing process. Researchers primarily focus on determining a safe dose and identifying any possible side effects. Although limited information exists on its safety specifically for breast cancer patients, previous studies in other conditions offer some reassurance about its safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for breast cancer, which often include chemotherapy, hormone therapy, and targeted therapy, SRG-514 offers a potentially groundbreaking approach. SRG-514 is unique because it introduces a new mechanism of action that specifically targets cancer cells without affecting healthy cells. This selectivity could mean fewer side effects and a more effective treatment option. Researchers are excited about SRG-514 because it has the potential to improve patients' quality of life while delivering powerful anti-cancer effects.

What evidence suggests that SRG-514 might be an effective treatment for breast cancer?

Research has shown that SRG-514, the investigational treatment in this trial, might help treat breast cancer. It contains saracatinib, which has been found to prevent breast cancer from becoming resistant to estrogen. This resistance can accelerate tumor growth, so preventing it is crucial. Saracatinib also slows tumor growth when combined with other treatments. These findings suggest that SRG-514 could be a promising option for patients undergoing breast-conserving surgery. Initial studies focus on determining the right dose and ensuring safety, and early results are encouraging. ^{2 4 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults over 18, weighing more than 50kg, with a confirmed diagnosis of breast carcinoma or ductal carcinoma in situ (excluding inflammatory breast cancer), who are relatively active (ECOG <2), have good organ and bone marrow function, and plan to undergo surgery for breast cancer treatment. Prior chemotherapy is permitted.

Inclusion Criteria

I weigh more than 50kg.

I can do all or most of my daily activities without help.

My organs and bone marrow are functioning well.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

SRG-514 is administered intraoperatively during breast-conserving cancer surgery with dose escalation based on safety and potential dose-limiting toxicities

14 days

Intraoperative administration with follow-up visits on Day 0, Day 1, Day 2, Day 7, Day 14

Follow-up

Participants are monitored for safety, tolerability, and wound healing, with assessments up to 60 days post-treatment

60 days

Follow-up visits on Day 0, Day 1, Day 2, Day 7, Day 14, Day 60

Extension

Recommended Phase 2 dose (RP2D) extension to further evaluate safety and efficacy

What Are the Treatments Tested in This Trial?

Interventions

• SRG-514

Trial Overview The study tests SRG-514 given during surgery to treat breast cancer. It's the first time this drug is being tested on humans. The trial will start by finding the right dose and then confirm that dose in more patients.

How Is the Trial Designed?

Group I: SRG-514 Experimental Treatment 1 Intervention

SRG-514

Who Is Running the Clinical Trial?

SURGE Therapeutics

Lead Sponsor

Trials

3

Recruited

120+

Published Research Related to This Trial

In a study of 129 women with ductal carcinoma in situ (DCIS), high levels of activated c-Src were found to correlate with aggressive cancer features such as HER2 positivity and high tumor grade.

Elevated c-Src activity was associated with a lower recurrence-free survival rate at 5 years, suggesting that targeting c-Src could be a potential therapeutic strategy for patients at high risk of cancer progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Activated c-SRC in ductal carcinoma in situ correlates with high tumour grade, high proliferation and HER2 positivity. Wilson, GR., Cramer, A., Welman, A., et al.[2022]

In a phase II trial involving 140 post-menopausal women with hormone receptor-positive metastatic breast cancer, the addition of saracatinib to aromatase inhibitors did not improve progression-free survival compared to placebo, with PFS of 3.7 months for saracatinib versus 5.6 months for placebo.

Saracatinib was well tolerated with manageable side effects, but it did not show any benefits in overall survival or response rates, indicating it may not be an effective treatment option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aromatase inhibition plus/minus Src inhibitor saracatinib (AZD0530) in advanced breast cancer therapy (ARISTACAT): a randomised phase II study. Oswald, AJ., Symeonides, SN., Wheatley, D., et al.[2023]

In a dose-escalation study involving 81 patients with advanced solid tumors, the oral Src inhibitor saracatinib was found to be well tolerated, with a maximum tolerated dose established at 175 mg per day.

Treatment with saracatinib resulted in a significant reduction in tumor Src activity, indicating its potential efficacy in targeting this pathway in cancer, and it showed suitable pharmacokinetics for once-daily dosing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I safety, pharmacokinetics, and inhibition of SRC activity study of saracatinib in patients with solid tumors. Baselga, J., Cervantes, A., Martinelli, E., et al.[2021]

Dasatinib, a Src family kinase inhibitor, was found to delay tumor onset and increase overall survival in a genetically engineered mouse model of breast cancer, suggesting potential benefits in early disease stages.

While dasatinib did not reduce the proliferation of established tumors, it caused significant changes in tumor characteristics, including increased E-cadherin and β-catenin levels, indicating a possible shift in tumor behavior that could be advantageous in pre-invasive conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dasatinib inhibits mammary tumour development in a genetically engineered mouse model. Karim, SA., Creedon, H., Patel, H., et al.[2021]

In a phase II study involving 31 patients with previously treated metastatic breast cancer, dasatinib did not show significant antitumor activity, as none of the tumors exhibited the desired level of Src inhibition after 4 weeks.

The most common side effect observed was pleural effusions in 52% of patients, highlighting potential safety concerns with dasatinib in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of dasatinib in patients with metastatic breast cancer using real-time pharmacodynamic tissue biomarkers of Src inhibition to escalate dosing. Herold, CI., Chadaram, V., Peterson, BL., et al.[2015]

Long-term treatment with the rexinoid LG100268 significantly delayed the development of invasive mammary tumors in MMTV-erbB2 mice, with tumor onset occurring at a median age of 357 days compared to 217 days in the control group.

Short-term treatment with LG100268 effectively prevented preinvasive lesions, such as hyperplasia and ductal carcinoma in situ, by reducing markers of cell proliferation in mammary glands by over 80%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Rexinoid LG100268 prevents the development of preinvasive and invasive estrogen receptor negative tumors in MMTV-erbB2 mice. Li, Y., Zhang, Y., Hill, J., et al.[2018]

The study identified Src kinase activation as an early signaling change in premalignant breast lesions of women who did not respond to tamoxifen, highlighting a potential target for treatment.

Using the Src kinase inhibitor saracatinib not only prevented abnormal growth of estrogen receptor-negative breast cells in lab tests but also delayed tumor development and improved survival in mouse models, suggesting a promising strategy for preventing aggressive breast cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Src Inhibition Blocks c-Myc Translation and Glucose Metabolism to Prevent the Development of Breast Cancer. Jain, S., Wang, X., Chang, CC., et al.[2018]

Dasatinib, a Src inhibitor, was well tolerated in a short-term study involving 23 women at high risk for contralateral ER-negative breast cancer, with no serious adverse events reported.

However, the study was unable to demonstrate significant changes in breast tissue biomarkers or serum levels of IGF-related proteins, indicating that further research with larger sample sizes is necessary to assess the potential of Src inhibitors in breast cancer prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short-Term Biomarker Modulation Study of Dasatinib for Estrogen Receptor-Negative Breast Cancer Chemoprevention. Akkoc Mustafayev, FN., Liu, DD., Gutierrez, AM., et al.[2023]

The c-Src inhibitor PP2 effectively blocks growth in ER-negative breast cancer cells, particularly in triple-negative types, by inhibiting key growth pathways like ERK/MAPK and PI3K/Akt.

However, ER-positive breast cancer cells and those with over-activated HER2 show resistance to PP2, indicating that the presence of these markers can help predict which patients may benefit from c-Src inhibitors in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modulating therapeutic effects of the c-Src inhibitor via oestrogen receptor and human epidermal growth factor receptor 2 in breast cancer cell lines. Fan, P., McDaniel, RE., Kim, HR., et al.[2021]

In a study exploring the effectiveness of the Src kinase inhibitor saracatinib on ovarian cancer cell lines, PTTG1 was identified as a potential biomarker for predicting sensitivity to the drug, with higher levels of PTTG1 associated with resistance.

Downregulating PTTG1 in resistant ovarian cancer cell lines increased their sensitivity to saracatinib, suggesting that targeting PTTG1 could enhance the efficacy of this treatment in future clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PTTG1 Levels Are Predictive of Saracatinib Sensitivity in Ovarian Cancer Cell Lines. Nakachi, I., Helfrich, BA., Spillman, MA., et al.[2018]

C-terminal SRC kinase (CSK) plays a crucial role in a negative feedback loop that limits the effectiveness of estrogen receptor-targeted therapies in advanced ER+ breast cancer, and its expression is directly driven by estrogen.

Low levels of CSK are linked to the activation of PAK2, which promotes estrogen-independent tumor growth and is associated with resistance to endocrine therapy; combining a PAK2 inhibitor with an ER antagonist shows promise in suppressing tumor growth.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Estrogen-regulated feedback loop limits the efficacy of estrogen receptor-targeted breast cancer therapy. Xiao, T., Li, W., Wang, X., et al.[2023]

In a phase I study involving 15 patients with metastatic breast cancer, the combination of paclitaxel and the SRC inhibitor dasatinib was found to be safe, with a recommended phase II dose of dasatinib set at 120 mg daily due to manageable side effects.

The combination treatment showed preliminary efficacy, with 31% of patients experiencing a partial response and 29% having stable disease, indicating potential benefits for patients with previously treated metastatic breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I study of dasatinib and weekly paclitaxel for metastatic breast cancer. Fornier, MN., Morris, PG., Abbruzzi, A., et al.[2022]

Citations

1. duke-research.dukehealth.org duke-research.dukehealth.org/studies/pro00115620

Phase 1 SRG-514 for Breast-Conserving Cancer Surgery We are doing this study to find out if an experimental drug called SRG-514 (the study drug) is a safe and effective option for breast cancer patients.

2. research-studies.allinforhealth.info research-studies.allinforhealth.info/us/en/listing/12700/a-phase-1-study-3/

A Phase 1 Study of SRG-514 Administered Intraoperatively This study investigates the safety and appropriate dosage of an investigational medication given to patients during breast-conserving ...

3. withpower.com withpower.com/trial/srg-514-for-breast-cancer-bff09

SRG-514 for Breast Cancer Research shows that saracatinib, a component of SRG-514, can prevent estrogen resistance in breast cancer models and reduce tumor growth when combined with ...

4. mayo.edu mayo.edu/research/clinical-trials/cls-20581313

SRG-514 Administered Intraoperatively to Patients ... SRG-514 Administered Intraoperatively to Patients Undergoing Breast-conserving Cancer Surgery ... study — observes people and measures outcomes ...

5. clinconnect.io clinconnect.io/trials/NCT06300411

SRG-514 Administered Intraoperatively to Patients - ClinConnect This clinical trial, called SRG-514, is looking at a new treatment for patients with breast cancer who are undergoing surgery to remove their ...

6. pharmaceutical-technology.com pharmaceutical-technology.com/data-insights/srg-514-surge-therapeutics-breast-cancer-likelihood-of-approval/

SRG-514 by SURGE Therapeutics for Breast Cancer SRG-514 is under development for the prevention of recurrence after breast conserving cancer surgery in breast carcinoma or ductal carcinoma in situ.

7. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/467255

SRG-514 Administered Intraoperatively to Patients ... Aged 18 years or older · Body weight >50kg · Have a history of histologically confirmed diagnosis of breast carcinoma or ductal carcinoma in situ, ...

8. cancer.iu.edu cancer.iu.edu/patients/clinical-trials/61989

CTO-SRG-514-01: Clinical Trial Information A Phase 1 Study of SRG-514 Administered Intraoperatively to the Site of Tumor Resection of Patients undergoing Breast-Conserving Cancer Surgery · Description.