Superenhancer Inhibitor Minnelide in Advanced Refractory Adenosquamous Carcinoma of the Pancreas (ASCP)
- Conditions
- Adenosquamous Carcinoma of the Pancreas
- Interventions
- Registration Number
- NCT04896073
- Lead Sponsor
- National Cancer Institute (NCI)
- 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.
- Detailed Description
Background:
* Adenosquamous carcinoma of the pancreas (ASCP) is a highly aggressive variant of pancreatic ductal adenocarcinoma (PDA), the most common type of pancreas cancer.
* ASCP is estimated to account for 0.5-4% of the 55,000 people who are diagnosed with pancreatic cancer in the United States (U.S.) each year, making it a very rare tumor type.
* No prospective clinical trials specific to ASCP have ever been performed.
* Preclinical data in ASCP models indicate that an activated superenhancer network drives epigenetic changes which cause the prognostically unfavorable squamous differentiation.
* Genomic analysis of ASCP tumors identifies frequent amplification of MYC.
* Minnelide is a small molecule anti-superenhancer drug that inhibits MYC.
* The recommended dose of Minnelide has previously been established through clinical testing for other indications.
Primary Objective:
-To determine the single agent antitumor activity (disease control rate) of the anti-superenhancer agent Minnelide in participants with advanced, previously treated ASCP
Eligibility:
* Age \>= 18 years
* Histologically confirmed ASCP or high suspicion for ASCP based on histologic analysis for squamous markers
* Participants with metastatic or locally advanced unresectable disease and progression on at least 1 prior treatment regimen
Design:
* This is a phase II single cohort clinical trial with one arm.
* The number of evaluable participants needed for the primary endpoint is 25; maximum accrual set at 55 participants (accounting for screen failures and inevaluable participants).
* initial participants will receive Minnelide at 2 mg/day by mouth (PO) on Days 1-21 of a 28-day cycle.
* Later participants will receive a higher dose of 2.5 mg/day PO on the same schedule.
* Treatment will be continued for up to 12 cycles (1 year) in the absence of disease progression or unacceptable toxicity.
* Treatment response will be assessed by imaging every 2 cycles (8 weeks).
* Optional tumor biopsies will be requested mid-cycle 1 and at time of progression.
* A disease control rate of \>= 40% in this highly refractory population would constitute a positive study. Up to 12 participants will be treated initially. If 3 of the 12 participants have a response, then up to 13 additional participants will be entered to determine the true response rate.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 16
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Arm 1, Cohort 1, Minnelide in Advanced Adenosquamous Carcinoma of the Pancreas (ASCP) Minnelide Minnelide 2mg Days 1-21 of 28-day cycle (x12) Arm 1, Cohort 1, Minnelide in Advanced Adenosquamous Carcinoma of the Pancreas (ASCP) ECG Minnelide 2mg Days 1-21 of 28-day cycle (x12) Arm 1, Cohort 1, Minnelide in Advanced Adenosquamous Carcinoma of the Pancreas (ASCP) CT/MRI Minnelide 2mg Days 1-21 of 28-day cycle (x12) Arm 1, Cohort 1, Minnelide in Advanced Adenosquamous Carcinoma of the Pancreas (ASCP) Tumor Biopsy Minnelide 2mg Days 1-21 of 28-day cycle (x12)
- Primary Outcome Measures
Name Time Method 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 16 weeks 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.
- Secondary Outcome Measures
Name Time Method 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 Non-serious adverse events of Minnelide were assessed by the Common Terminology Criteria for Adverse Events (CTCAE). A non-serious adverse event is any untoward medical occurrence. Grade 2 is moderate. Grade 3 is severe. Grade 4 is life-threatening. Grade 5 is death related to adverse events.
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 Serious adverse events of Minnelite were assessed by the Common Terminology Criteria for Adverse Events (CTCAE). A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned. Grade 2 is moderate. Grade 3 is severe. Grade 4 is life-threatening. Grade 5 is death related to adverse events.
Progression Free Survival (PFS) start of treatment to time of progression or death, a median of 1.76 months PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first. PFS will be determined using the Kaplan-Meier method and reported along with a 95% confidence interval for the median. Progression was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Progressive Disease is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. The appearance of one or more new lesions is also considered progressions.
Overall Survival (OS) time from the start of treatment until death, a median of 4.91 months OS is defined as the length of time from the start of treatment until death. OS will be determined by using the Kaplan-Meier method and reported along with a 95% confidence interval for the median.
Objective Response Rate (ORR) From start of treatment until radiological progression response or off study; the median is approximately 6 weeks Objective response rate (ORR) will be calculated as the percentage of participants with Complete Response (CR) or Partial Response (PR) as defined by Response Evaluation Criteria in Solid Tumors (RECIST)1.1 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.
Trial Locations
- Locations (1)
National Institutes of Health Clinical Center
🇺🇸Bethesda, Maryland, United States
National Institutes of Health Clinical Center🇺🇸Bethesda, Maryland, United States