ProAgio + Gemcitabine for Breast Cancer

Recruiting at 1 trial location

Overseen By Damon Michaels

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: ProDa BioTech, LLC

Must not be taking: Gemcitabine

Disqualifiers: Cardiac disease, Neurologic disorders, Pregnancy, others

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

Compensation: Varies

Number of Visits: 6

51 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety and effectiveness of a new treatment combination, ProAgio and Gemcitabine, for individuals with metastatic triple-negative breast cancer. Researchers seek to determine how well this duo works and whether it causes any side effects. Suitable participants should have previously tried at least two other unsuccessful treatments and must have confirmed triple-negative breast cancer that has spread. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive it.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you must be more than 14 days removed from your most recent standard or experimental cancer treatment before joining the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Studies have shown that ProAgio, when combined with Gemcitabine, is safe and generally well-tolerated. Earlier research tested ProAgio at various doses, and patients tolerated it well at all levels, indicating that the treatment does not cause severe side effects at those doses. Gemcitabine, already used to treat breast cancer, is known for its safety, particularly in combination with other treatments. Although some side effects may occur, previous findings suggest that the combination remains manageable. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about ProAgio combined with Gemcitabine for breast cancer because it offers a fresh approach compared to standard treatments like hormone therapies, chemotherapy, and targeted therapies. ProAgio is unique because it specifically targets the tumor's blood vessels, potentially cutting off the cancer's blood supply and starving it, which is different from the typical direct attack on cancer cells. This innovative mechanism could enhance the effectiveness of Gemcitabine, a well-known chemotherapy drug, making the combination a promising candidate for improved outcomes in breast cancer treatment.

What evidence suggests that this trial's treatments could be effective for metastatic triple negative breast cancer?

Research has shown that combining gemcitabine with other drugs, such as anthracyclines, achieves response rates of 33% to 89% in treating advanced breast cancer. Various studies have also demonstrated the effectiveness of gemcitabine alone for advanced breast cancer. In this trial, participants will receive a combination of ProAgio and gemcitabine. ProAgio targets a protein called αvβ3 integrin, which aids cancer cell growth. Early research suggests that combining ProAgio with gemcitabine might enhance treatment effectiveness against metastatic triple-negative breast cancer. Although this combination remains under study, it is being tested to determine if it can improve outcomes for patients with this challenging condition. ^{1 2 3 4 6}

Who Is on the Research Team?

Kevin M Kalinsky, MD

Principal Investigator

Emory University Winship Cancer Institute

Are You a Good Fit for This Trial?

This trial is for patients with metastatic triple negative breast cancer. Details about who can join are not fully provided, but typically participants must meet certain health standards and have no conflicting conditions.

Inclusion Criteria

I have undergone at least two treatments for my advanced illness.

I can take care of myself but might not be able to do heavy physical work.

I agree to use birth control during the study.

Exclusion Criteria

I have a heart condition or have been treated with heart-toxic drugs and need a heart function assessment.

I have not had uncontrolled bleeding in the last 28 days.

I have been treated with gemcitabine for cancer that has spread.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive ProAgio combined with Gemcitabine by intravenous injections on days 1, 8, 15 every 4-week cycle to identify the maximum tolerated dose

Variable, up to 2 years

3 visits per 4-week cycle (in-person)

Dose Expansion

Participants receive ProAgio at the objective response rate combined with Gemcitabine by intravenous injections on days 1, 8, 15 every 4-week cycle to estimate the objective response rate

Variable, up to 2 years

3 visits per 4-week cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Gemcitabine
• ProAgio

Trial Overview The study is testing the safety and effectiveness of ProAgio, a new anti-cancer drug targeting specific proteins on cancer cells, combined with Gemcitabine, a chemotherapy medication.

How Is the Trial Designed?

Group I: Dose Expansion Experimental Treatment 1 Intervention

Participants will receive ProAgio at the objective response rate (ORR) combined with Gemcitabine is administered to study participants by intravenous injections on days 1, 8, 15 every 4-week Cycle. Other Names: ACT50, and Gemcitabine

Group II: Dose Escalation Experimental Treatment 1 Intervention

Experimental: Dose Escalation ProAgio Dose Levels (DL) 1,2,3,4 ProAgio combined with Gemcitabine is administered to study participants by intravenous injections on days 1, 8, 15, every 4-week Cycle. Other Names: ACT50, and Gemcitabine

Gemcitabine is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in United States as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in Canada as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in Japan as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Who Is Running the Clinical Trial?

ProDa BioTech, LLC

Lead Sponsor

Trials

3

Recruited

140+

Emory University

Collaborator

Trials

1,735

Recruited

2,605,000+

Georgia State University

Collaborator

Trials

71

Recruited

33,600+

Published Research Related to This Trial

Gemcitabine has shown single-agent efficacy in advanced breast cancer with response rates up to 42% and is well tolerated with mild side effects, making it a strong candidate for combination therapies.

In combination with anthracyclines, gemcitabine has demonstrated overall response rates between 33%-89% in advanced breast cancer and up to 95% in early-stage disease, indicating its potential effectiveness in various treatment settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine/anthracycline combinations in metastatic breast cancer. Zielinski, CC.[2022]

In a study involving 39 chemotherapy-naive patients with stage IIIB breast cancer, the combination of gemcitabine and doxorubicin as neoadjuvant therapy resulted in a high overall response rate of 95%, with 18% achieving a complete response and 77% a partial response.

The treatment was associated with moderate toxicity, including hematologic issues like neutropenia and leukopenia, but overall, 83% of treatment cycles were administered at full dose, indicating a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of neoadjuvant gemcitabine plus doxorubicin in stage IIIB breast cancer: a preliminary report. Gomez, H., Kahatt, C., Falcon, S., et al.[2022]

Neoadjuvant chemotherapy, including gemcitabine combined with anthracyclines and taxanes, is becoming standard for treating locally advanced breast cancer and may improve surgical options for earlier-stage patients.

Preliminary results from phase II trials indicate that gemcitabine combined with doxorubicin or paclitaxel leads to higher complete response rates and is well-tolerated, suggesting it could enhance treatment outcomes for breast cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant gemcitabine therapy for breast cancer. Sánchez-Rovira, P., Jaén, A., Dueñas, R., et al.[2022]

Gemcitabine (Gemzar) has shown significant antitumor activity in breast cancer treatment, providing better outcomes without excessive toxicity, making it a promising option for patients.

In combination with paclitaxel, gemcitabine has established itself as a first-line treatment, improving response rates and survival, and is currently being investigated for its role in early-stage breast cancer as part of neoadjuvant therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Integrating gemcitabine into breast cancer therapy. Yardley, DA.[2022]

In a study of 30 breast cancer patients who had previously failed chemotherapy, the combination of gemcitabine and cisplatin showed a 52% overall response rate, indicating its effectiveness across various disease subgroups.

The treatment was associated with manageable toxicity, primarily hematologic, with significant side effects including grade 3/4 neutropenia in 37% of patients and nausea/vomiting in 12%, suggesting a tolerable safety profile for this regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine plus cisplatin (GC): a salvage regimen for advanced breast cancer patients who have failed anthracycline and/or taxane therapy. Chitapanarux, I., Lorvidhaya, V., Kamnerdsupaphon, P., et al.[2022]

Gemcitabine has shown a response rate of 25% to 46% as a single agent in treating advanced breast cancer, with even higher rates when combined with other cytotoxic drugs.

The combination of gemcitabine and cisplatin demonstrates significant synergy and effectiveness in relapsed breast cancer patients, indicating it may be a promising option for those resistant to other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine plus cisplatin in breast cancer. Nagourney, RA.[2022]

In a phase III study involving 397 postmenopausal women with metastatic breast cancer, epirubicin significantly outperformed gemcitabine in terms of time to progression (6.1 months vs. 3.4 months) and overall survival (19.1 months vs. 11.8 months).

Epirubicin also had a higher response rate (40.3% vs. 16.4%) compared to gemcitabine, while both treatments were generally well tolerated, with common severe side effects including neutropenia and leukopenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line gemcitabine versus epirubicin in postmenopausal women aged 60 or older with metastatic breast cancer: a multicenter, randomized, phase III study. Feher, O., Vodvarka, P., Jassem, J., et al.[2022]

In a phase II study involving 42 women with metastatic breast cancer, the combination of gemcitabine and doxorubicin resulted in a 55% overall response rate, indicating significant efficacy as a first-line treatment.

The treatment was found to be safe, with the main side effects being hematologic, and the pharmacokinetics of both drugs remained unchanged when administered together, suggesting they can be effectively combined without altering their effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine in combination with doxorubicin in advanced breast cancer: final results of a phase II pharmacokinetic trial. Pérez-Manga, G., Lluch, A., Alba, E., et al.[2022]

Gemcitabine has shown significant antitumor activity in metastatic breast cancer, achieving response rates of up to 37% in first-line treatment and remaining effective in second-line (26%) and third-line (18%) settings across nine studies.

As a combination therapy, gemcitabine enhances efficacy when paired with other agents, particularly in triple-drug regimens, yielding response rates as high as 58-92%, making it a valuable option for both first-line and heavily pretreated patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of gemcitabine in the treatment of advanced and metastatic breast cancer. Heinemann, V.[2022]

Gemcitabine shows significant antitumor activity in metastatic breast cancer, with response rates of 16% to 37% when used alone, and up to 80% when combined with other chemotherapy agents in phase II trials.

Its mild toxicity profile makes gemcitabine a promising candidate for combination therapies with targeted treatments like trastuzumab and tyrosine kinase inhibitors, potentially enhancing its efficacy in managing metastatic breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine and targeted therapy in metastatic breast cancer. Qu, G., Perez, EA.[2022]

Gemcitabine shows promise as a treatment for advanced breast cancer, with response rates of 14-37% as a first-line therapy and 12-30% as salvage therapy, indicating its potential effectiveness even after other treatments have been tried.

When combined with other chemotherapy agents like vinorelbine and anthracyclines, gemcitabine has achieved response rates of 50-80% in phase II studies, suggesting that it may enhance treatment outcomes when used in combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rationale for the use of gemcitabine in breast cancer (Review). Silvestris, N., D'Aprile, M., Andreola, G., et al.[2022]

Citations

1. withpower.com withpower.com/trial/phase-2-triple-negative-breast-neoplasms-6-2024-dd5b5

ProAgio + Gemcitabine for Breast Cancer In combination with anthracyclines, gemcitabine has demonstrated overall response rates between 33%-89% in advanced breast cancer and up to 95% in early-stage ...

2. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-07988

ProAgio in Combination With Gemcitabine in Patients ... This is a Phase I/II Trial Evaluating the Safety and Efficacy of ProAgio, an anti- αvβ3 Integrin Cytotoxin, in Combination with Gemcitabine in Patients with ...

3. georgiacancerinfo.org georgiacancerinfo.org/trialDetailPrint.aspx?trialID=5866

Clinical Trial Details | GCI ProAgio in Combination With Gemcitabine in Patients With Metastatic Triple Negative Breast Cancer ; Eligibility: 18 Years and older, Male and Female, Study Type: ...

4. centerwatch.com centerwatch.com/clinical-trials/listings/NCT06460298/proagio-in-combination-with-gemcitabine-in-patients-with-metastatic-triple-negative-breast-cancer

ProAgio in Combination With Gemcitabine in Patients ... This is a single-arm, Phase I/II study, designed to evaluate the safety and efficacy of the combination of ProAgio with gemcitabine in patients ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5805543/

Gemcitabine-based chemotherapy as a viable option for ... This meta-analysis was designed to compare the efficacy and safety of gemcitabine-based regimens for the treatment advanced breast cancer (ABC).

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.e16336

Phase I study of ProAgio, an αvβ3 integrin cytotoxin, in ... Conclusions: ProAgio is safe and well-tolerated at all dose levels. A dose expansion phase of 15 participants will begin enrolling once RP2D is ...