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

58 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug Galeterone combined with Gemcitabine for pancreatic cancer?

Research shows that Galeterone, when combined with Gemcitabine, can significantly inhibit the growth and spread of pancreatic cancer cells in lab studies and reduce tumor growth in mice. This combination targets specific pathways that help cancer cells survive and resist treatment, making it a promising option for further development. ^{1 2 3 4 5}

Is the combination of Galeterone and Gemcitabine safe for humans?

Gemcitabine is known to have a favorable side-effect profile, making it generally safe for use in humans. Galeterone, primarily studied for prostate cancer, is in phase III clinical development, indicating it has passed initial safety evaluations. However, specific safety data for the combination of Galeterone and Gemcitabine in humans is not provided in the available research. ^{2 3 6 7 8}

What makes the drug combination of Galeterone and Gemcitabine unique for pancreatic cancer?

This drug combination is unique because Galeterone targets specific pathways (Mnk1/2-eIF4E and NF-κB) that are involved in pancreatic cancer progression and resistance to Gemcitabine, potentially enhancing the effectiveness of Gemcitabine and overcoming resistance in pancreatic cancer cells. ^{1 2 3 9 10}

What is the purpose of this trial?

Assess the effectiveness of galeterone in advanced pancreatic adenocarcinoma

Research Team

Aaron Ciner, MD

Principal Investigator

University of Maryland, Baltimore

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

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

2. United States 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. [2018]

3. United States pubmed.ncbi.nlm.nih.gov

Present and future treatment of pancreatic cancer. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

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

5. England 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). [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Effects of the proteasome inhibitor bortezomib on gene expression profiles of pancreatic cancer cells. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Andrographis Reverses Gemcitabine Resistance through Regulation of ERBB3 and Calcium Signaling Pathway in Pancreatic Ductal Adenocarcinoma. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Gemcitabine elaidate and ONC201 combination therapy inhibits pancreatic cancer in a KRAS mutated syngeneic mouse model. [2023]

9. Belgium pubmed.ncbi.nlm.nih.gov

[Gemcitabine: a new chemotherapy agent for solid cancers]. [2022]

10. United Arab Emirates pubmed.ncbi.nlm.nih.gov

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