Superenhancer Inhibitor Minnelide in Advanced Refractory Adenosquamous Carcinoma of the Pancreas (ASCP)

NCT04896073 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 10000254000254-C
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Pancreatic cancer is one of the most lethal types of cancer. American Society for Clinical Pathology (ASCP) is a highly aggressive type of pancreatic cancer. It is very rare. 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. Eligibility: Adults ages 18 and older with ASCP whose cancer did not respond to previous treatments. Design: Participants will be screened with: Medical history Physical exam Blood and urine samples Evaluation of ability to do daily activities Electrocardiogram to test heart function Body and/or brain scans. For these, participants will lie in a machine that takes pictures of the body. They may have a contrast agent injected into a vein. Tumor sample. If one is not available, participants will have a tumor biopsy. The biopsy will be taken with a small needle put through the skin into the tumor. Treatment will be given in 28-day cycles, for up to 12 cycles. There is a 7-day resting period between cycles. Participants will take Minnelide by mouth every day for 21 days of each cycle. They will keep a medicine diary. Participants will have at least 1 study visit every cycle. They will review their medicine diary. They will repeat some screening tests. Participants may have optional tumor biopsies. Some participants may need to take birth control during the study and for up to 6 months after treatment. Participants will have an end-of-treatment visit 4 weeks after they stop taking the study drug. They will repeat some screening tests.

Conditions

Adenosquamous Carcinoma of the Pancreas

Keywords

Pancreatic Ductal Adenocarcinoma; epigenetic changes; MYC; triptolide; HSP70

Outcome Measures

Primary Outcomes (1)

• Proportion of Evaluable Participants Who Experience Clinical Benefit (Disease Control Rate = Complete Response (CR)+Partial Response (PR)+Stable Disease x16 Weeks) Reported Along With a 95% Confidence Interval

  To determine the single agent antitumor activity (disease control rate = CR + PR + stable disease x16 weeks) of the anti-superenhancer agent Minnelide in participants with advanced, previously treated adenosquamous carcinoma of the pancreas (ASCP) using Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Complete Response is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in short axis to \<10 mm. Partial Response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters. Stable Disease is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum of diameters while on study. Progressive Disease is least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study.

  16 weeks

Secondary Outcomes (5)

• Number of Participants Who Experience a Non-serious Grade 2 or Higher Toxicity, by Grade and Type of Toxicity Assessed by the Common Terminology Criteria for Adverse Events (CTCAE)

  Non-serious adverse events related to Minnelide that occur from start of treatment to 30 days after last treatment

• Number of Participants Who Experience a Serious Grade 2 or Higher Toxicity, by Grade and Type of Toxicity Assessed by the Common Terminology Criteria for Adverse Events (CTCAE)

  Serious adverse events related to Minnelide that occur from start of treatment to 30 days after last treatment

• Progression Free Survival (PFS)

  start of treatment to time of progression or death, a median of 1.76 months

• Overall Survival (OS)

  time from the start of treatment until death, a median of 4.91 months

• Objective Response Rate (ORR)

  From start of treatment until radiological progression response or off study; the median is approximately 6 weeks

Other Outcomes (1)

• Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)

  Adverse Events were monitored/assessed from the first study intervention, Study Day 1 of Cycle 1 through 30 days after the study agent (s) was/were administered

Study Arms (1)

Arm 1, Cohort 1, Minnelide in Advanced Adenosquamous Carcinoma of the Pancreas (ASCP)

EXPERIMENTAL

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

Drug: Minnelide; Diagnostic Test: ECG; Diagnostic Test: CT/MRI; Procedure: Tumor Biopsy

Interventions

Minnelide DRUG

Administered orally (2 mg) once daily for 21 days of 28-day cycles for 12 cycles.

Also known as: 14-O-phosphonooxymethyltriptolide-disodium-salt and Minnelide-001

Arm 1, Cohort 1, Minnelide in Advanced Adenosquamous Carcinoma of the Pancreas (ASCP)

ECG DIAGNOSTIC_TEST

Screening and end of treatment visit.

Also known as: Electrocardiogram

Arm 1, Cohort 1, Minnelide in Advanced Adenosquamous Carcinoma of the Pancreas (ASCP)

CT/MRI DIAGNOSTIC_TEST

Screening. Subsequent cycles Day 1 (≤3days) and Day 15 (±2 days) (every other cycle). End of treatment visit.

Also known as: Computed tomography/Magnetic resonance imaging

Arm 1, Cohort 1, Minnelide in Advanced Adenosquamous Carcinoma of the Pancreas (ASCP)

Tumor Biopsy PROCEDURE

Optional. Baseline Cycle 1, Day 1 and Cycle 1, Day 15. End of treatment visit or progressive disease.

Also known as: Tumor Bx

Arm 1, Cohort 1, Minnelide in Advanced Adenosquamous Carcinoma of the Pancreas (ASCP)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histological or cytological diagnosis of adenosquamous carcinoma of the pancreas (ASCP) or high suspicion for ASCP as confirmed by National Institutes of Health (NIH) Laboratory of Pathology. ASCP will be defined as \>=30% malignant squamous component in background of typical pancreatic ductal adenocarcinoma (PDA). If malignant squamous component is identified in the sample, but the pathologist is unable to determine whether it is \>= 30%, then the participant will be considered to have high suspicion for ASCP.
• Note: To meet this criterion, participant must be able to submit a suitable archival tumor specimen (primary or metastatic site) for review or currently have tumor in a location deemed low risk for core biopsy so that suitable tissue can be acquired for confirmation of diagnosis. Note that cytopathology specimens are not considered suitable for definitive diagnosis of ASCP but can be used to determine high suspicion for ASCP.
• Participants with metastatic, recurrent or locally advanced unresectable disease and progression or intolerance to at least 1 prior systemic treatment regimen in the advanced disease setting.
• Disease measurable by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.
• Progressive disease as evidenced by increasing tumor size on radiologic assessment, increasing serum tumor marker (on last 2 measurements taken at least 1 week apart), increasing ascites, and/or worsening tumor-related symptoms such as weight loss, pain, gastrointestinal (GI) upset.
• Age \>18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status \<2 (Karnofsky \>60%).
• Be willing and able to provide written informed consent for the trial.
• Participants must have adequate organ and marrow function as defined below:
• absolute neutrophil count (ANC) \>= 1,500/microL
• platelets \>= 100,000/microL
• hemoglobin \>= 9.0 g/dL or \>= 5.6 mmol/La\*
• Creatinine \<= 1.5 x ULN
• measured or calculated \*bcreatinine clearance (Glomerular filtration rate (GFR) can also be used in place of creatinine or CrCl) \>= 45 mL/min for participant with creatinine levels \>1.5 x institutional upper limit of normal (ULN)
• total bilirubin \<= 1.5 x ULN OR direct bilirubin \<= ULN for participants with total bilirubin levels \>1.5 x ULN

You may not qualify if:

• Has uncontrolled vomiting or medical condition which inhibits oral ingestion or digestion because the study treatment is administered orally.
• Pregnant and/or women who are breast feeding are excluded from this study because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with Minnelide.
• Is currently participating and receiving trial therapy or has participated in a trial of an investigational agent/therapy or used an investigational device within 3 weeks of the first planned treatment on this study.
• Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to Cycle 1/Day 1
• Requires use of ondansetron or another prohibited medication. Note that other 5-hydroxytryptamine 3 (5-HT3) inhibitors are NOT prohibited.
• Has received major surgery within the last 4 weeks, minor endoscopic procedure such as biliary stenting within the last 2 weeks, or percutaneous procedure such as hepatic biopsy or celiac plexus block within 24 hours of planned treatment start date. Note: participant must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
• Participants with previously treated brain metastases may participate if:
• a) follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression at \>= 4 weeks since treatment, AND b) participant has stability of baseline neurologic symptoms without receiving immunosuppressive-doses of systemic corticosteroid (physiologic replacement doses are permitted) x7 days or increases in other supportive medications that treat neurologic symptoms such as antiepileptics x14 days. Participants with carcinomatous meningitis are excluded regardless of clinical stability.
• Has an active infection requiring systemic therapy.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the participant s participation for the full duration of the trial, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• Has known uncontrolled or poorly controlled human immunodeficiency virus (HIV) infection. HIV is considered uncontrolled or poorly controlled if an HIV-infected individual is not taking highly active anti-retroviral therapy or has a detectable viral load within the previous 6 months.
• Has active hepatitis B virus (HBV) or hepatitis C virus (HCV) or is currently under treatment for HBV or HCV. Active HBV or HCV does not include previously cleared HBV or HCV or successfully cured HBV or HCV through treatment

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (1)

• Skorupan N, Ahmad MI, Steinberg SM, Trepel JB, Cridebring D, Han H, Von Hoff DD, Alewine C. A phase II trial of the super-enhancer inhibitor Minnelide in advanced refractory adenosquamous carcinoma of the pancreas. Future Oncol. 2022 Jun;18(20):2475-2481. doi: 10.2217/fon-2021-1609. Epub 2022 May 10.

  PMID: 35535581 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Interventions

14-O-phosphonooxymethyltriptolide disodium salt; Electrocardiography; Tomography, X-Ray Computed; Magnetic Resonance Imaging

Intervention Hierarchy (Ancestors)

Heart Function Tests; Diagnostic Techniques, Cardiovascular; Diagnostic Techniques and Procedures; Diagnosis; Electrodiagnosis; Image Interpretation, Computer-Assisted; Diagnostic Imaging; Radiographic Image Enhancement; Image Enhancement; Photography; Radiography; Tomography, X-Ray; Tomography

Results Point of Contact

• Title: Dr. Anish Thomas
• Organization: National Cancer Institute

anish.thomas@nih.gov

240-760-7343

Study Officials

• Anish Thomas, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 20, 2021
• First Posted: May 21, 2021
• Study Start: March 7, 2022
• Primary Completion: March 30, 2025
• Study Completion: March 30, 2025
• Last Updated: October 7, 2025
• Results First Posted: October 7, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Clinical data available during the study and indefinitely. Genomic data is available once genomic data is uploaded per protocol Genomic Data Sharing (GDS) plan for as long as database is active.
• Access Criteria: Clinical data will be made available via subscription to Biomedical Translational Research Information System (BTRIS) and with the permission of the study principal investigator (PI). Genomic data is made available via the database of Genotypes and Phenotypes (dbGaP) through requests to the data custodians.

Locations

US (1)