Galeterone +/− Gemcitabine for Pancreatic Cancer

Overseen By Aaron Ciner, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Maryland, Baltimore

Must not be taking: Anti-androgens

Disqualifiers: Heart failure, Hepatitis, HIV, 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

Duration: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for advanced pancreatic cancer using galeterone, a hormone therapy, with or without gemcitabine, a chemotherapy drug. Researchers aim to determine if galeterone alone or combined with gemcitabine manages the disease better than current treatments. Participants must have metastatic pancreatic cancer and have tried at least two other unsuccessful treatments. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering a chance to contribute to potentially groundbreaking advancements in pancreatic cancer therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot use other anti-cancer agents while participating. You also must not have received chemotherapy for at least 4 weeks before starting the trial.

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

Research has shown that galeterone has mostly been used to treat prostate cancer, but it is now being tested for pancreatic cancer. Studies indicate that it can slow the growth of cancer cells and help kill them. This suggests potential effectiveness against cancer, but further testing is needed to ensure safety.

When combined with gemcitabine, a drug already approved for cancer treatment, the results appear promising. Gemcitabine is known for mild side effects, making it generally safe for patients. Together, these drugs aim to be more effective in treating pancreatic cancer.

Participants in previous studies tolerated these treatments well, but like any drug, side effects can occur. It is important for anyone considering joining a trial to consult with their healthcare providers and understand the possible risks and benefits. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Galeterone and Gemcitabine for pancreatic cancer because they offer unique approaches to treatment. Galeterone is known for targeting androgen receptors, which is a different mechanism from traditional chemotherapy options that typically target rapidly dividing cells. When combined with Gemcitabine, a standard chemotherapy drug, it could potentially enhance the treatment's effectiveness by attacking cancer cells from two angles. This combination could provide a more powerful and potentially more effective treatment pathway for patients with pancreatic cancer.

What evidence suggests that this trial's treatments could be effective for pancreatic cancer?

Research has shown that combining galeterone with gemcitabine can significantly slow the growth of pancreatic cancer cells in lab studies. This trial will test two separate treatment arms: one where participants receive both galeterone and gemcitabine, and another where participants receive only galeterone. Although galeterone alone has not shown any effect in humans with advanced pancreatic cancer, it has been safe to use. The combination treatment aims to enhance results by using both drugs together. The goal is to determine if adding gemcitabine to galeterone improves cancer treatment. This approach is based on promising lab results and the need for better treatment options for pancreatic cancer. ^{1 3 5 6 7}

Who Is on the Research Team?

Aaron Ciner, MD

Principal Investigator

University of Maryland, Baltimore

Are You a Good Fit for This Trial?

This trial is for adults over 18 with advanced pancreatic adenocarcinoma who have tried at least two other treatments without success. They must be able to take oral medication, have a life expectancy of more than 12 weeks, and agree to use effective contraception. People with controlled brain metastasis may join, but not those with HIV, recent major surgery or radiation therapy, certain heart conditions, uncontrolled blood pressure issues, or active severe infections.

Inclusion Criteria

I can take care of myself and am up and about more than half of the day.

I have been diagnosed with pancreatic cancer.

You have confirmed spread of the disease that can be measured to be at least 1cm in size using a CT or MRI scan.

Exclusion Criteria

Your heart beats too slowly, less than 50 beats per minute.

I have not had a fainting spell or mini-stroke in the last year.

You are currently misusing alcohol or using illegal drugs.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive galeterone alone or in combination with gemcitabine for pancreatic cancer

8 weeks

Daily oral doses of galeterone, weekly gemcitabine

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Long-term follow-up

Participants are monitored for overall survival and progression-free survival

Up to 100 months

What Are the Treatments Tested in This Trial?

Interventions

• Galeterone
• Gemcitabine

Trial Overview The study tests the effectiveness of galeterone alone or combined with gemcitabine in treating metastatic pancreatic cancer. Participants will receive these medications to see if they help control the disease better than previous therapies they've had.

How Is the Trial Designed?

Group I: galeterone+gemcitabine Experimental Treatment 2 Interventions

daily dose galeterone and weekly dose of gemcitabine

Group II: galeterone Experimental Treatment 1 Intervention

galeterone orally once daily

Who Is Running the Clinical Trial?

University of Maryland, Baltimore

Lead Sponsor

Trials

729

Recruited

540,000+

Published Research Related to This Trial

In a Phase I/II study involving 18 patients with advanced pancreatic cancer, the combination of docetaxel and gemcitabine was tested, with docetaxel's maximum tolerable dose determined to be 70 mg/m2 due to significant toxicities like neutropenia.

The results showed that the combination therapy only led to one partial response and a median survival of 5.4 months, indicating that adding docetaxel does not provide additional benefits over gemcitabine alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I-II study of gemcitabine and docetaxel in advanced pancreatic cancer: a report from the Italian Group for the Study of Digestive Tract Cancer (GISCAD). Cascinu, S., Gasparini, G., Catalano, V., et al.[2022]

The study identified key transcription factors that drive cancer-related genes in pancreatic ductal adenocarcinoma (PDAC), highlighting the EGF/VEGF signaling pathway as a major contributor to drug resistance against gemcitabine.

By understanding how gemcitabine-induced hypoxia affects apoptosis and cell proliferation through this pathway, targeting its upstream components may offer new strategies for improving treatment outcomes in PDAC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Understanding the Mechanism of Cell Death in Gemcitabine Resistant Pancreatic Ductal Adenocarcinoma: A Systems Biology Approach. Aier, I., Varadwaj, PK.[2023]

Single-agent gemcitabine is still the standard treatment for advanced pancreatic cancer, but recent phase III trials have not shown improved survival with most combinations of gemcitabine and other chemotherapy drugs.

The combination of gemcitabine with erlotinib has been linked to a significant increase in survival, and ongoing trials are exploring the effectiveness of gemcitabine with bevacizumab and other biologic agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent updates on the role of chemotherapy in pancreatic cancer. Burris, HA.[2022]

Galeterone and its analogs significantly inhibited the growth of pancreatic cancer cells, both in gemcitabine-naive and gemcitabine-resistant cell lines, suggesting they could overcome resistance to standard chemotherapy.

These compounds not only induced cell death and cell cycle arrest but also downregulated key signaling pathways and factors associated with cancer progression, leading to reduced cell migration and invasion, and showed promising tumor growth inhibition in animal models.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Galeterone and its analogs inhibit Mnk-eIF4E axis, synergize with gemcitabine, impede pancreatic cancer cell migration, invasion and proliferation and inhibit tumor growth in mice. Kwegyir-Afful, AK., Murigi, FN., Purushottamachar, P., et al.[2018]

Andrographis (Andro) can enhance the effectiveness of Gemcitabine (Gem) chemotherapy in pancreatic ductal adenocarcinoma (PDAC) by reversing drug resistance, as shown in in vitro experiments with Gem-resistant PDAC cells and patient-derived 3D-organoids.

The mechanism involves down-regulating ERBB3 expression and decreasing intracellular calcium levels, which are linked to poor prognosis in PDAC patients, indicating that targeting these pathways could improve treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Andrographis Reverses Gemcitabine Resistance through Regulation of ERBB3 and Calcium Signaling Pathway in Pancreatic Ductal Adenocarcinoma. Okuno, K., Xu, C., Pascual-Sabater, S., et al.[2023]

Gemcitabine is a promising chemotherapy drug for various cancers, including pancreatic, lung, ovarian, and breast cancers, and is favored for its low toxicity, primarily affecting blood cells, making it suitable for patients who cannot handle more aggressive treatments.

When combined with other anticancer drugs like cisplatin and anthracyclines, gemcitabine shows high response rates, and it also enhances the effectiveness of radiotherapy, particularly in locally advanced cancer cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Gemcitabine: a new chemotherapy agent for solid cancers]. Klastersky, J., Awada, A.[2022]

Bortezomib enhances the effectiveness of gemcitabine in treating pancreatic cancer by altering the gene expression profile of cancer cells, particularly in those with varying sensitivity to gemcitabine, as shown in a study using pancreatic cancer cell lines BxPC-3 and PANC-1.

The study identified 44 genes that were significantly up-regulated by bortezomib, including the repression of the anti-apoptotic gene Bcl-2, suggesting that bortezomib may promote cancer cell death and could be a promising therapeutic target in pancreatic cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of the proteasome inhibitor bortezomib on gene expression profiles of pancreatic cancer cells. Tang, ZY., Wu, YL., Gao, SL., et al.[2022]

Gemcitabine has changed the perception of pancreatic cancer treatment, showing good tolerability and low side effects, making it a viable option for combination therapies with drugs like cisplatin and 5-fluorouracil.

Combination regimens with gemcitabine and cisplatin have shown response rates between 11.4% and 58% and median survival times of 7.4 to 10 months, while gemcitabine with 5-FU has lower response rates and survival times, indicating the need for further optimization of treatment combinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine-based combination treatment of pancreatic cancer. Heinemann, V.[2022]

Gemcitabine is now considered a standard treatment for advanced pancreatic cancer due to its effectiveness and favorable side-effect profile.

While combinations of gemcitabine with other antitumor drugs and biological agents have shown promise in phase II trials, none have yet been established as an evidence-based standard treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Present and future treatment of pancreatic cancer. Heinemann, V.[2022]

The combination of ONC201 and lipid-gemcitabine (L_GEM) significantly inhibits the growth of pancreatic cancer cells by blocking the AKT/ERK pathways, which helps overcome drug resistance.

ONC201 has a strong safety profile and enhances the effectiveness of gemcitabine, suggesting that this dual-targeting approach could improve treatment outcomes in pancreatic cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine elaidate and ONC201 combination therapy inhibits pancreatic cancer in a KRAS mutated syngeneic mouse model. Mahato, R., Kumar, V., Sethi, B., et al.[2023]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.4_suppl.744

Galeterone monotherapy in advanced pancreatic ductal ... Conclusions: Galeterone showed no clinical activity, but with a favorable safety profile, as a single-agent in heavily pre-treated patients with ...

2. aacrjournals.org aacrjournals.org/cancerres/article/75/15_Supplement/1764/600682/Abstract-1764-Galeterone-and-its-novel-analogs

Galeterone and its novel analogs induce profound anti-cancer ... Pancreatic cancer is a lethal disease with a 3-5% survival rate. Histologically, 90% of human pancreatic cancer is presented as pancreatic.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04098081?term=GALETERONE&viewType=Table&rank=3

1911GCCC: Galeterone With Gemcitabine for Patients With ... Galeterone is an androgen receptor inhibitor that showed anti-cancer activity in pancreatic cancer in research lab. In this study, the investigator is ...

4. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2020-00208

Galeterone Combined with Gemcitabine for the Treatment ... This phase II trial studies how well an investigational agent called galeterone works in combination with gemcitabine for the treatment of pancreatic cancer

5. withpower.com withpower.com/trial/galeterone-gemcitabine-for-pancreatic-cancer-80cec

Galeterone +/− Gemcitabine for Pancreatic Cancer Trial Overview The study tests the effectiveness of galeterone alone or combined with gemcitabine in treating metastatic pancreatic cancer. Participants will ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5581036/

Galeterone and its analogs inhibit Mnk-eIF4E axis ... Survival rate for pancreatic cancer (pancreatic ductal adenocarcinoma, PDAC) is poor, with about 80% of patients presenting with the metastatic disease.

7. sciencedirect.com sciencedirect.com/science/article/pii/S0304419X25002100

Steroidal derivatives in pancreatic cancer: Paving the way ... Results showed a dose-dependent decrease in both cancer cell lines' proliferation, along with a cell cycle arrest at phase G2/M and cell death ...