Minnelide for Pancreatic Cancer

Overseen By Christine C Alewine, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Ondansetron

Disqualifiers: Pregnancy, CNS metastases, 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: 3

Duration: 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called Minnelide (a Triptolide prodrug) to determine its effectiveness in treating adenosquamous carcinoma of the pancreas (ASCP), a rare and aggressive type of pancreatic cancer. Researchers aim to discover if Minnelide can benefit patients whose cancer has not responded to other treatments. Participants will take the drug for 21 days in a 28-day cycle, repeating this for up to 12 cycles. Suitable candidates include adults with ASCP whose cancer has not improved with previous treatments and who experience worsening symptoms like weight loss or pain. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

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

Research has shown that Minnelide has been tested for safety in people with gastrointestinal (GI) cancers. In an initial human study, researchers identified a dose and schedule for Minnelide that was generally well-tolerated. While some side effects might occur, they are usually manageable.

Minnelide has been used in patients with advanced, difficult-to-treat GI cancers, such as pancreatic cancer. Although specific safety details from the studies aren't provided here, ongoing research suggests a reasonable level of safety. Participants will be closely monitored for any side effects, as the treatment is still under study. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Minnelide is unique because it targets pancreatic cancer with a novel approach. Unlike current treatments, such as chemotherapy with drugs like gemcitabine or nab-paclitaxel, Minnelide works by disrupting heat shock protein 70 (HSP70), a crucial protein that helps cancer cells survive and proliferate. This mechanism can potentially lead to more effective results in killing cancer cells. Researchers are excited about Minnelide because it offers a targeted attack on the cancer's survival mechanisms, which could translate to better outcomes for patients with advanced adenocarcinoma of the pancreas.

What evidence suggests that Minnelide might be an effective treatment for ASCP?

Research has shown that Minnelide, the investigational treatment in this trial, might help treat adenosquamous carcinoma of the pancreas (ASCP), a rare and aggressive form of pancreatic cancer. Studies have found that Minnelide can halt tumor growth and, in some cases, reduce tumor size. The drug also seems to slow the spread of cancer to other parts of the body. These findings are promising, especially given the limited treatment options for this type of cancer. While more research is needed, these early results suggest that Minnelide could become an important treatment for ASCP. ^{1 2 3 5 6}

Who Is on the Research Team?

Anish Thomas, M.D.

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive Minnelide orally for 21 days in a 28-day cycle, up to 12 cycles

12 months

At least 1 visit per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

Long-term follow-up

Participants are monitored for overall survival and progression-free survival

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Minnelide

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.

How Is the Trial Designed?

Group I: Arm 1, Cohort 1, Minnelide in Advanced Adenosquamous Carcinoma of the Pancreas (ASCP) Experimental Treatment 4 Interventions

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+

Published Research Related to This Trial

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 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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9344435/

A phase II trial of the super-enhancer inhibitor Minnelide ... This phase II trial tests the efficacy of Minnelide in patients with advanced refractory ASCP. Adenosquamous carcinoma of the pancreas (ASCP) is ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04896073

NCT04896073 | Superenhancer Inhibitor Minnelide in ... Researchers want to see if a drug called Minnelide can be used to treat ASCP. Objective: To see if Minnelide is an effective treatment for ASCP.

3. academic.oup.com academic.oup.com/oncolo/article/29/2/132/7505299

First-in-Human Phase I Study of Minnelide in Patients With ... This first-in-human, phase I clinical study identified a dose and schedule of Minnelide in patients with refractory GI cancers.

4. pancreasfoundation.org pancreasfoundation.org/wp-content/uploads/2021/04/Minnelide-STM-2012.pdf

Chugh 1..10 Our data so far demonstrated that Minnelide administration could not only prevent tumor progression but also induce tumor regression, reduce metastasis, and ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35535581/

A phase II trial of the super-enhancer inhibitor Minnelide™ in ... Adenosquamous carcinoma of the pancreas (ASCP) is a rare and highly aggressive variant of pancreatic cancer, with limited treatment options. Changes in ...

6. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/73/NCT04896073/Prot_SAP_000.pdf

Minnelide for ASCP Version Date: 7/10/2025 ASCP is estimated to account for 0.5-4% of the 55,000 people who are diagnosed with pancreatic cancer in the U.S. each year, making it a very rare tumor type. • ...