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.
12345What 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.
13456Is 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.
13478Eligibility 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.
+6 more
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.
+12 more
Participant Groups
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.
1Treatment groups
Experimental Treatment
Group I: 1/MinnelideExperimental Treatment1 Intervention
Minnelide 2mg Days 1-21 of 28 day cycle (x12)
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
National Institutes of Health Clinical CenterBethesda, MD
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Who Is Running the Clinical Trial?
National Cancer Institute (NCI)Lead Sponsor
References
Minnelide synergizes with conventional chemotherapy by targeting both cancer and associated stroma components in pancreatic cancer. [2023]Addition of nab-paclitaxel to gemcitabine offers a survival benefit of only 6 weeks over gemcitabine alone at a cost of increased toxicity in PDAC. The goal of the present study is to evaluate the efficacy of Minnelide, a water-soluble prodrug of triptolide, in combination with the standard of care regimen for chemotherapy with the added advantage of reducing the doses of these drugs to minimize toxicity. Pancreatic cancer cell lines were implanted subcutaneously or orthotopically in athymic nude or C57BL/6J mice. Subsequently, animals were randomized and received saline or minnelide or full dose chemotherapy or low dose chemotherapy or minnelide in combination with low dose chemotherapy. Our results show that a combination of low doses of Minnelide with Gemcitabine + nab-paclitaxel significantly inhibited tumor progression and increased the survival of tumor-bearing mice in comparison with conventional chemotherapy alone. Moreover, combination therapy significantly reduced cancer-related morbidity by decreasing ascites and metastasis and effectively targeted both cancer and the associated stroma. In vitro studies with a combination of low doses of triptolide and paclitaxel significantly decreased the cell viability, increased apoptosis and led to significantly increased M-phase cell cycle arrest in various pancreatic cancer cell lines as compared to either drug alone. Our results show that Minnelide synergizes with conventional chemotherapy leading to a significant reduction in the doses of these toxic drugs, all the while achieving better efficacy in the treatment of PDAC. This combination effectively targeted both the cancer and the associated stromal components of pancreatic cancer.
Triptolide induces cell death in pancreatic cancer cells by apoptotic and autophagic pathways. [2021]Pancreatic adenocarcinoma, among the most lethal human malignancies, is resistant to current chemotherapies. We previously showed that triptolide inhibits the growth of pancreatic cancer cells in vitro and prevents tumor growth in vivo. This study investigates the mechanism by which triptolide kills pancreatic cancer cells.
Triptolide and Its Derivatives as Cancer Therapies. [2020]Triptolide, a compound isolated from a Chinese medicinal herb, possesses potent antitumor, immunosuppressive, and anti-inflammatory properties, but is clinically limited due to its poor solubility, bioavailability, and toxicity. Recently, Minnelide, a water-soluble prodrug of triptolide, was shown to have potent antitumor activity in various preclinical cancer models. Minnelide is currently in Phase II clinical trials for treatment of advanced pancreatic cancer, which has fueled increased interest in this promising agent. Here, we review the recent advances in the biological activity of triptolide and its analogs, their mechanisms of actions, and their clinical developments. A special emphasis is given to proteins and pathways within the tumor and stromal compartments that are targeted by triptolide and its analogs as well as the ongoing clinical trials.
Inhibition of epithelial ovarian cancer by Minnelide, a water-soluble pro-drug. [2021]Minnelide is a water-soluble pro-drug of triptolide, a natural product. The goal of this study was to evaluate the effectiveness of Minnelide on ovarian cancer growth in vitro and in vivo.
A novel triptolide analog downregulates NF-kB and induces mitochondrial apoptosis pathways in human pancreatic cancer. [2023]Pancreatic cancer is the seventh leading cause of cancer-related death worldwide, and despite advancements in disease management, the 5-year survival rate stands at only 12%. Triptolides have potent anti-tumor activity against different types of cancers, including pancreatic cancer, however poor solubility and toxicity limit their translation into clinical use. We synthesized a novel pro-drug of triptolide, (E)-19-[(1'-benzoyloxy-1'-phenyl)-methylidene]-Triptolide (CK21), which was formulated into an emulsion for in vitro and in vivo testing in rats and mice, and using human pancreatic cancer cell lines and patient-derived pancreatic tumor organoids. A time-course transcriptomic profiling of tumor organoids treated with CK21 in vitro was conducted to define its mechanism of action, as well as transcriptomic profiling at a single time point post-CK21 administration in vivo. Intravenous administration of emulsified CK21 resulted in the stable release of triptolide, and potent anti-proliferative effects on human pancreatic cancer cell lines and patient-derived pancreatic tumor organoids in vitro, and with minimal toxicity in vivo. Time course transcriptomic profiling of tumor organoids treated with CK21 in vitro revealed <10 differentially expressed genes (DEGs) at 3 h and ~8,000 DEGs at 12 h. Overall inhibition of general RNA transcription was observed, and Ingenuity pathway analysis together with functional cellular assays confirmed inhibition of the NF-κB pathway, increased oxidative phosphorylation and mitochondrial dysfunction, leading ultimately to increased reactive oxygen species (ROS) production, reduced B-cell-lymphoma protein 2 (BCL2) expression, and mitochondrial-mediated tumor cell apoptosis. CK21 is a novel pro-drug of triptolide that exerts potent anti-proliferative effects on human pancreatic tumors by inhibiting the NF-κB pathway, leading ultimately to mitochondrial-mediated tumor cell apoptosis.
Minnelide: a novel therapeutic that promotes apoptosis in non-small cell lung carcinoma in vivo. [2022]Minnelide, a pro-drug of triptolide, has recently emerged as a potent anticancer agent. The precise mechanisms of its cytotoxic effects remain unclear.
Downregulation of Sp1 by Minnelide leads to decrease in HSP70 and decrease in tumor burden of gastric cancer. [2021]Gastric cancer is the third leading cause of cancer related mortality worldwide with poor survival rates. Even though a number of chemotherapeutic compounds have been used against this disease, stomach cancer has not been particularly sensitive to these drugs. In this study we have evaluated the effect of triptolide, a naturally derived diterpene triepoxide and its water soluble pro-drug Minnelide on several gastric adenocarcinoma cell lines both as monotherapy and in combination with CPT-11.
Minnelide reduces tumor burden in preclinical models of osteosarcoma. [2023]Osteosarcoma is the most common bone cancer in children and adolescents with a 5-year survival rate of about 70%. In this study, we have evaluated the preclinical therapeutic efficacy of the novel synthetic drug, Minnelide, a prodrug of triptolide on osteosarcoma. Triptolide was effective in significantly inducing apoptosis in all osteosarcoma cell lines tested but had no significant effect on the human osteoblast cells. Notably, Minnelide treatment significantly reduced tumor burden and lung metastasis in the orthotopic and lung colonization models. Triptolide/Minnelide effectively downregulated the levels of pro-survival proteins such as heat shock proteins, cMYC, survivin and targets the NF-κB pathway.