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

  • STATUS
    Recruiting
  • End date
    Sep 1, 2026
  • participants needed
    55
  • sponsor
    National Cancer Institute (NCI)
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Updated on 24 July 2022
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Summary

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.

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 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
  • 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).
  • All participants will receive Minnelide at 2 mg/day PO on Days 1-21 of a 28 day cycle.
  • 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.

Details
Condition Adenosquamous Carcinoma of the Pancreas
Treatment Minnelide
Clinical Study IdentifierNCT04896073
SponsorNational Cancer Institute (NCI)
Last Modified on24 July 2022

Eligibility

 Yes No Not Sure

Inclusion Criteria

Histological or cytological diagnosis of ASCP as confirmed by NIH Laboratory of Pathology. ASCP will be defined as >= 30% malignant squamous component in background of typical PDA
Note: To meet this criteria, 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 diagnosis of
ASCP
Participants with metastatic, recurrent or locally advanced unresectable disease and
Disease measurable by RECIST 1.1 criteria
progression or intolerance to at least 1 prior systemic treatment regimen in the
advanced disease setting
Age >18 years
ECOG performance status <2 (Karnofsky >60%)
Progressive disease as evidenced by increasing tumor size on radiologic assessment
Be willing and able to provide written informed consent for the trial
increasing serum tumor marker (on last 2 measurements taken at least 1 week apart)
Participants must have adequate organ and marrow function as defined below
increasing ascites, and/or worsening tumor-related symptoms such as weight loss, pain
absolute neutrophil count (ANC) >= 1,500/microL
GI upset
platelets >= 100,000/microL
hemoglobin >= 9.0 g/dL or >= 5.6 mmol/La
Creatinine <= 1.5 x ULN
OR
International normalized ratio (INR) OR
measured or calculated bcreatinine clearance (GFR can also be used in place of creatinine
prothrombin time (PT)
or CrCl) >= 45 mL/min for participant with creatinine levels >1.5 x institutional ULN
activated partial thromboplastin time (aPTT)
total bilirubin <= 1.5 x ULN OR direct bilirubin <= ULN for participants with total
bilirubin levels >1.5 x ULN
AST (SGOT) and ALT (SGPT) <= 2.5 x ULN (<= 5 x ULN for participants with liver
metastases)
transfusion within last 2 weeks
<= 1.5 x ULN unless participant is receiving anticoagulant therapy as long as PT or PTT is
b Creatinine clearance (CrCl) should be calculated per institutional standard
within therapeutic range of intended use of anticoagulants
ALT (SGPT) = alanine aminotransferase (serum glutamic pyruvic transaminase); AST (SGOT) =
aspartate aminotransferase (serum glutamic oxaloacetic transaminase); GFR = glomerular
filtration rate; ULN=upper limit of normal
a Criteria must be met without erythropoietin dependency and without packed red blood cell
(pRBC)
Note: This table includes eligibility-defining laboratory value requirements for treatment
laboratory value requirements should be adapted according to local regulations and
guidelines for the administration of specific chemotherapies
The effects of Minnelide on the developing human fetus are unknown. For this reason, women
of child-bearing potential (WOCBP) and men must agree to use adequate contraception
(hormonal or barrier method of birth control; abstinence) prior to study entry, for the
duration of study participation, and for 6 months (women) and 3 months (men) after the last
dose of trial treatment. Male participants must also refrain from donating sperm during
this period. Should a woman become pregnant or suspect she is pregnant while she or her
partner is participating in this study, she should inform her treating physician
immediately

Exclusion Criteria

Participants with previously treated brain metastases may participate if
Has an active infection requiring systemic therapy
Has uncontrolled vomiting or medical condition which inhibits oral ingestion or
digestion because the study treatment is administered orally
Has received a live vaccine within 30 days of planned start of trial therapy
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-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
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 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 HBV or 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
Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and
are allowed; however intranasal influenza vaccines (e.g. Flu-Mist (Registered Trademark))
are live attenuated vaccines, and are not allowed
History of allergic reactions attributed to compounds of similar chemical or biologic
composition to Minnelide
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