Clinical Trials /

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

NCT04896073

Description:

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.

Related Conditions:
  • Pancreatic Adenosquamous Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Superenhancer Inhibitor Minnelide in Advanced Refractory Adenosquamous Carcinoma of the Pancreas (ASCP)
  • Official Title: A Phase II Trial of the Superenhancer Inhibitor Minnelide in Advanced Refractory Adenosquamous Carcinoma of the Pancreas (ASCP)

Clinical Trial IDs

  • ORG STUDY ID: 10000254
  • SECONDARY ID: 000254-C
  • NCT ID: NCT04896073

Conditions

  • Adenosquamous Carcinoma of the Pancreas

Interventions

DrugSynonymsArms
Minnelide1/Minnelide

Purpose

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.

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 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.
    

Trial Arms

NameTypeDescriptionInterventions
1/MinnelideExperimentalMinnelide 2mg Days 1-21 of 28 day cycle (x12)
  • Minnelide

Eligibility Criteria

        -  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
             progression or intolerance to at least 1 prior systemic treatment regimen in the
             advanced disease setting.

          -  Disease measurable by 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,
             GI upset.

          -  Age >18 years.

          -  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

        OR

        measured or calculated *bcreatinine clearance (GFR can also be used in place of creatinine
        or CrCl) >= 45 mL/min for participant with creatinine levels >1.5 x institutional ULN

          -  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)

          -  International normalized ratio (INR) OR

               -  prothrombin time (PT)

               -  activated partial thromboplastin time (aPTT):

        <= 1.5 x ULN unless participant is receiving anticoagulant therapy as long as PT or PTT is
        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)

        transfusion within last 2 weeks.

        *b Creatinine clearance (CrCl) should be calculated per institutional standard.

        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:

          -  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-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 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

          -  Has received a live vaccine within 30 days of planned start of trial therapy.

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:disease control rate
Time Frame:16 weeks
Safety Issue:
Description:To determine the single agent antitumor activity (disease control rate = CR+PR+stable x16 weeks) of the anti-superenhancer agent Minnelide in participants with advanced, previously treated ASCP

Secondary Outcome Measures

Measure:safety and tolerability of Minnelide
Time Frame:duration of treatment
Safety Issue:
Description:AEs and SAEs of Minnelite
Measure:progression free survival (PFS)
Time Frame:start of treatment to 30 days after last treatment
Safety Issue:
Description:frequency and grade of AEs and SAEs
Measure:Overall Survival (OS)
Time Frame:through 1 year after last Minnelide treatment in the last subject who completes treatment
Safety Issue:
Description:The length of time from the start of treatment that patients diagnosed with the disease are still alive.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:National Cancer Institute (NCI)

Trial Keywords

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

Last Updated

September 1, 2021