Minnelide for Pancreatic Cancer

Overseen by Christine Alewine, MD, PhD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Waitlist Available

Sponsor: National Cancer Institute (NCI)

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial is testing Minnelide, a pill taken by mouth, to treat a rare and aggressive type of pancreatic cancer called ASCP. The trial targets adults whose cancer did not respond to previous treatments. Minnelide works by blocking a protein that helps the cancer grow, potentially controlling the disease.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot use ondansetron or other prohibited medications, and you must not have had chemotherapy, targeted therapy, or radiation therapy within 2 weeks before starting the trial.

What data supports the idea that Minnelide for Pancreatic Cancer is an effective drug?

The available research shows that Minnelide, when combined with low doses of standard chemotherapy drugs like Gemcitabine and nab-paclitaxel, significantly slows down tumor growth and increases survival in mice with pancreatic cancer compared to using chemotherapy alone. This combination also reduces the side effects typically associated with high doses of chemotherapy. Additionally, Minnelide effectively targets both the cancer cells and the surrounding supportive tissue, which helps in controlling the disease more effectively. ^{1 2 3 4 5}

What safety data exists for Minnelide in treating pancreatic cancer?

Minnelide, a water-soluble prodrug of triptolide, has shown potent antitumor activity in preclinical models of pancreatic cancer. It is currently in Phase II clinical trials for advanced pancreatic cancer. Studies indicate that Minnelide can synergize with conventional chemotherapy, allowing for reduced doses of toxic drugs while maintaining efficacy. This combination has been shown to significantly inhibit tumor progression and reduce cancer-related morbidity in animal models. However, triptolide, the active compound, is known for its toxicity, which has limited its clinical use. Minnelide aims to address these limitations by improving solubility and bioavailability, but detailed safety data from human trials is still emerging. ^{1 3 4 5 6}

Is the drug Minnelide a promising treatment for pancreatic cancer?

Yes, Minnelide is a promising drug for pancreatic cancer. It works well with standard chemotherapy, helping to reduce the amount of toxic drugs needed while still effectively fighting the cancer. This combination not only slows down tumor growth but also improves survival rates and reduces cancer-related complications. ^{1 3 4 7 8}

Research Team

Christine Alewine, MD, PhD

Principal Investigator

National Cancer Institute (NCI)

Eligibility Criteria

Adults over 18 with advanced refractory adenosquamous carcinoma of the pancreas (ASCP) that didn't respond to prior treatments. Participants must have a certain level of physical ability, adequate organ function, and measurable disease. They should not be pregnant or breastfeeding and must agree to use contraception during the trial and for some time after.

Inclusion Criteria

Be willing and able to provide written informed consent for the trial.

My cancer is getting worse, shown by tests or new/worsening symptoms.

My organs and bone marrow are functioning well.

Exclusion Criteria

I haven't had cancer treatment in the last 2 weeks.

I need to take ondansetron or another medication that is not allowed in this trial.

I have another cancer besides the one being studied, but it's not getting worse or needing treatment.

Treatment Details

Interventions

• Minnelide (Superenhancer Inhibitor)

Trial Overview The trial is testing Minnelide's effectiveness against ASCP. Patients will take Minnelide orally for 21 days in each 28-day cycle, up to 12 cycles, documenting their intake in a diary. The study includes regular visits for health checks and may involve optional tumor biopsies.

Participant Groups

Group I: 1/Minnelide Experimental Treatment 1 Intervention

Minnelide 2mg Days 1-21 of 28 day cycle (x12)

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Dr. Douglas R. Lowy

National Cancer Institute (NCI)

Chief Executive Officer since 2023

MD from New York University School of Medicine

Dr. Monica Bertagnolli

National Cancer Institute (NCI)

Chief Medical Officer since 2022

MD from Harvard Medical School

Findings from Research

The study found that combining low doses of Minnelide with standard chemotherapy (Gemcitabine and nab-paclitaxel) significantly improved survival and reduced tumor progression in mice with pancreatic cancer compared to conventional chemotherapy alone.

Minnelide not only enhanced the effectiveness of the chemotherapy but also reduced toxicity by allowing for lower doses of the drugs, while effectively targeting both cancer cells and the surrounding supportive tissue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Minnelide synergizes with conventional chemotherapy by targeting both cancer and associated stroma components in pancreatic cancer. Modi, S., Giri, B., Gupta, VK., et al.[2023]

Triptolide effectively induces cell death in pancreatic cancer cells through two distinct mechanisms: apoptosis in certain cell lines (MiaPaCa-2, Capan-1, BxPC-3) and autophagy in others (S2-013, S2-VP10, Hs766T), making it a versatile treatment option.

The study highlights that triptolide's autophagy-inducing effects are pro-death and involve specific autophagy-related genes, while also affecting key signaling pathways, suggesting its potential as a novel chemotherapeutic agent against various pancreatic cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Triptolide induces cell death in pancreatic cancer cells by apoptotic and autophagic pathways. Mujumdar, N., Mackenzie, TN., Dudeja, V., et al.[2021]

Minnelide, a water-soluble prodrug of triptolide, shows strong antitumor activity in preclinical models and is currently being tested in Phase II clinical trials for advanced pancreatic cancer, addressing the limitations of triptolide's poor solubility and toxicity.

The review highlights the mechanisms of action of triptolide and its analogs, focusing on their effects on specific proteins and pathways in tumors and surrounding tissues, which could enhance their therapeutic potential.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Triptolide and Its Derivatives as Cancer Therapies. Noel, P., Von Hoff, DD., Saluja, AK., et al.[2020]

Minnelide effectively reduces the viability of both platinum-sensitive and resistant ovarian cancer cells in laboratory tests, indicating its potential as a treatment option.

In mouse models, Minnelide not only increased survival when used alone but also enhanced the effectiveness of standard chemotherapy drugs like carboplatin and paclitaxel, suggesting it could be a valuable addition to ovarian cancer treatment regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhibition of epithelial ovarian cancer by Minnelide, a water-soluble pro-drug. Rivard, C., Geller, M., Schnettler, E., et al.[2021]

CK21, a novel pro-drug of triptolide, shows potent anti-tumor effects against pancreatic cancer with minimal toxicity in vivo, making it a promising candidate for clinical use.

The mechanism of action for CK21 involves the inhibition of the NF-κB pathway, leading to increased production of reactive oxygen species (ROS) and ultimately causing apoptosis in pancreatic tumor cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel triptolide analog downregulates NF-kB and induces mitochondrial apoptosis pathways in human pancreatic cancer. Tian, Q., Zhang, P., Wang, Y., et al.[2023]

Minnelide, a pro-drug of triptolide, has shown significant anti-cancer effects in non-small cell lung carcinoma (NSCLC) by inducing cell death (apoptosis) and inhibiting cell growth in both laboratory and animal studies.

The mechanism of action involves down-regulating pro-survival genes and up-regulating pro-apoptotic genes, primarily through the inhibition of NF-κB signaling, suggesting a targeted approach to enhance cancer treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Minnelide: a novel therapeutic that promotes apoptosis in non-small cell lung carcinoma in vivo. Rousalova, I., Banerjee, S., Sangwan, V., et al.[2022]

Triptolide and its pro-drug Minnelide significantly reduced cell viability and increased apoptosis in gastric cancer cell lines MKN28 and MKN45, indicating their potential effectiveness as treatments.

In animal models, Minnelide not only reduced tumor burden when used alone but also showed enhanced efficacy when combined with CPT-11, leading to significantly smaller tumors, which supports its ongoing phase 1 clinical trials for gastrointestinal cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Downregulation of Sp1 by Minnelide leads to decrease in HSP70 and decrease in tumor burden of gastric cancer. Arora, N., Alsaied, O., Dauer, P., et al.[2021]

Minnelide, a prodrug of triptolide, shows promising preclinical efficacy against osteosarcoma by significantly reducing tumor burden and lung metastasis in experimental models.

Triptolide effectively induces apoptosis in osteosarcoma cells without harming normal human osteoblast cells, and it works by downregulating pro-survival proteins and targeting the NF-κB pathway.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Minnelide reduces tumor burden in preclinical models of osteosarcoma. Banerjee, S., Thayanithy, V., Sangwan, V., et al.[2023]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

Minnelide synergizes with conventional chemotherapy by targeting both cancer and associated stroma components in pancreatic cancer. [2023]

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

Triptolide induces cell death in pancreatic cancer cells by apoptotic and autophagic pathways. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Triptolide and Its Derivatives as Cancer Therapies. [2020]

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

Inhibition of epithelial ovarian cancer by Minnelide, a water-soluble pro-drug. [2021]

5. England pubmed.ncbi.nlm.nih.gov

A novel triptolide analog downregulates NF-kB and induces mitochondrial apoptosis pathways in human pancreatic cancer. [2023]

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

Minnelide: a novel therapeutic that promotes apoptosis in non-small cell lung carcinoma in vivo. [2022]

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

Downregulation of Sp1 by Minnelide leads to decrease in HSP70 and decrease in tumor burden of gastric cancer. [2021]

8. Ireland pubmed.ncbi.nlm.nih.gov

Minnelide reduces tumor burden in preclinical models of osteosarcoma. [2023]