Adenosquamous Carcinoma of the Pancreas Clinical Trial
Official title:
A Phase II Trial of the Superenhancer Inhibitor Minnelide in Advanced Refractory Adenosquamous Carcinoma of the Pancreas (ASCP)
Background: Pancreatic cancer is one of the most lethal types of cancer. 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.
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 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). - iNITIALparticipants will receive Minnelide at 2 mg/day 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 treated be 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. ;