Neoplasms

Digestive System Diseases

All Conditions

Rare Diseases

Stomach Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Stomach Diseases

Stomach Cancer

Antineoplastic Agents

All Drugs and Chemicals

Paclitaxel

Albumin-Bound Paclitaxel

14-O-phosphonooxymethyltriptolide disodium salt

Antineoplastic Agents, Alkylating

Alkylating Agents

at the MTD dose level established for monotherapy or combination to confirm safety. With a sample of 12 patients, the probability is \> 80% that a serious adverse event with at least a 16% incidence will be detected.

Minnelide

Mohana Velagapudi, MD

EUNKYUNG Park, RN

Jeeyun Lee, MD

Mohana Velagapudi

A Phase 1, Open-label, Dose-Escalation, Safety, Pharmacokinetic and Pharmacodynamic Study of Minnelide™ Capsules given alone or in combination with paclitaxel in patients with Advanced Gastric Cancer.

Minnelide™ is a water soluble disodium salt variant of triptolide, a diterpenoid, an HSP70 inhibitor. Studies using orthotopic pancreatic cancer cell lines and human xenograft transplants demonstrate that Minnelide™ prevents tumor progression, increases survival, and causes tumor regression.

Minnelide™ Capsules Alone and in Combination With Paclitaxel in Advanced Gastric Cancer

A Phase 1 Open-Label, Dose-Escalation, Safety, Pharmacokinetic, and Pharmacodynamic Study of Minnelide™ Capsules Given Alone or in Combination With Paclitaxel in Patients With Advanced Gastric Cancer

To observe any increase in the number of patients that experience Grade 4 neutropenia lasting ≥ 5 days or Grade 3 or 4 neutropenia with fever and/or infection; Grade 4 thrombocytopenia (or Grade 3 with bleeding); Grade 3 or 4 treatment-related non-hematological toxicity (Grade 3 nausea, vomiting or diarrhea that last \> 72 hours despite maximal treatment when Minnelide is given alone and in combination with paclitaxel compared to the incidence with gemcitabine and nab-paclitaxel.

Area under the concentration curve (AUC) will be determine the exposure of Minnelide

Maximum plasma concentration (Cmax) will be measured to determine the effect of Minnelide when given with paclitaxel

Minneamrita Therapeutics LLC

Gland and Hormone Related Diseases

Pancreatic Neoplasms

Endocrine Gland Neoplasms

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

0.67 mg/m2 Minnelide daily as a 30min iv infusion on days 1-21 of each 28 day cycle, followed by a 7 day rest period (D 22-28).

Minnelide will be administered at the dose of 0.67 mg/m2 as a 30 min infusion intravenously daily on days 1-21 of each cycle followed by a 7 day rest period (days 22-28).

David Propper

Erkut Borazanci

MinPAC aims to see if the drug Minnelide can slow down tumour growth in patients with pancreatic cancer that is not responding to treatment. Minnelide is designed to rapidly release the anti-tumour molecule triptolide in the bloodstream and has been shown to slow cancer cell growth and induce cancer cell death. Minnelide is currently being investigated in other early phase trials and has shown promising response data.

There are strict eligibility criteria for this trial. Broadly speaking, patients with pancreatic cancer that has spread to other organs and has progressed on one or more chemotherapy regimens are eligible. Participants will receive Minnelide on days 1-21 of each 28 day cycle until their cancer stops responding to treatment. After that participants will be followed up 3 monthly for the collection of disease status and survival data.

MinPAC includes biological and imaging studies. Participants will be asked to donate tumour and blood samples and will be asked to undergo additional PET Scans. The study is being carried out in 4 sites in the UK and USA.

MinPAC is an open label, international, multicentre phase II trial that aims to evaluate the effects of Minnelide treatment in patients with refractory pancreatic cancer. Eligible patients will receive Minnelide until disease progression unless there is evidence of unacceptable toxicity or the patient requests to be withdrawn from the study treatment. Once disease progression is documented, patients will enter a follow up phase during which data will be collected on further disease and survival status. If patients are unable to attend hospital visits during the follow up period then data will be collected either via telephone or via national registries with the patient's consent. The efficacy of Minnelide will be assessed on CT/MRI scan images and tumour and/or blood samples collected at baseline, during treatment and on completion of treatment.

A Phase II, International Open Label Trial of Minnelide™ in Patients With Refractory Pancreatic Cancer

MinPAC: A Phase II, International Open Label Trial of Minnelide™ in Patients With Refractory Pancreatic Cancer.

Changes in circulating tumour stem cells.

Time from enrolment until disease progression or death from any cause, whichever occurs first (RECIST v1.1)

Percentage of individuals on study attaining a CR + PR (RECIST v1.1)

Change in the sum of diameters of the target lesions

Percentage of patients with \>20% decrease

Barts & The London NHS Trust

Translational Genomics Research Institute

Stand Up To Cancer

Cancer Research UK

Lustgarten Foundation

Queen Mary University of London

Blood and Lymph Conditions

Symptoms and General Pathology

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Shock

Neoplasms by Histologic Type

Hematologic Diseases

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Dose Level -1: 25% decrease from prior dose level

- 0.40 mg/m2 administered intravenously on days 1-5, 8-12, and 15-19 of a 28 day cycle

Starting Dose Level 1:

* 0.53 mg/m2 administered intravenously on days 1-5, 8-12, and 15-19 of a 28 day cycle

Dose Level 2: 25% increase from Dose Level 1

- 0.67 mg/m2 administered intravenously on days 1-5, 8-12, and 15-19 of a 28 day cycle

Dose Level 3: 25% increase from Dose Level 2

- 0.80 mg/m2 administered intravenously on days 1-5, 8-12, and 15-19 of a 28 day cycle

Minnelide therapy may be administered for up to 12 cycles of 28 days are planned. If patients are receiving clinical benefit, treatment can continue beyond 12 cycles.

Justin Watts, MD

Minnelide, a water-soluble disodium salt variant of triptolide, is a diterpenoid heat shock protein 70 (HSP70) inhibitor. Studies using AML cell lines, primary patient samples, and mouse transplant models demonstrate that Minnelide has potent cell killing effects. Minnelide has already been developed for human use and given to patients in a phase I trial for gastrointestinal (GI) cancers. Given the clinical safety profile and preliminary activity described in human GI cancers, the low-nanomolar anti-leukemic potency of triptolide in vitro, and that minnelide doses predicted to be significantly below the maximum tolerated dose (MTD) in human GI cancers decreased leukemia burden in animal models, the investigators propose a phase I trial in acute myeloid leukemia (AML).

This is a Phase 1, open label, dose-escalation, safety, pharmacokinetic, and pharmacodynamic pilot study of minnelide given to adult patients with relapsed or refractory AML.

The patient population will consist of adults previously diagnosed with relapsed/refractory AML for whom standard curative or life-prolonging treatment is unavailable or is no longer effective. Patients who are on hydroxyurea may be included in the study and may continue on hydroxyurea while participating in this study.

Once enrolled into the study, patients will be administered Minnelide via a 30-minute IV infusion. Each 28-day treatment cycle is composed of 5 consecutive daily doses of Minnelide followed by a 2-day rest period, repeating for 21 days, followed by a 7-day rest period.

Minnelide therapy may be administered for up to at least 12 cycles provided that the patient tolerates treatment and there is evidence of clinical benefit. If patients are still receiving clinical benefit, treatment may continue beyond 12 cycles, depending on drug availability and drug manufacturer (Minneamrita®) agreement. Study drug may be discontinued early if a patient experiences study drug related toxicities. Patients may discontinue therapy at any time. Patients will attend an End-of-Study visit 30 (+/- 10) days after receiving their last dose of study drug.

To determine the MTD of minnelide, an approach using traditional "3+3" escalation rules will be used. Dose-limiting toxicity (DLT) will be defined as events that are considered by the investigator to be related to therapy with minnelide. Although DLTs may occur at any point during treatment, only DLTs occurring during Cycle 1 of treatment will influence decisions regarding dose escalation. The initial minnelide dose will be 0.53 mg/m2 per dose; (3 dose levels will be explored; 0.53 mg/m2, 0.67 mg/m2, and 0.80 mg/m2). If more than 1 DLT occurs at Dose Level 1, then the next dose to be evaluated (Dose Level -1) will be 0.40 mg/m2. If more than 1 DLT occurs at Dose Level -1, the investigators will consider stopping the study. More conservative dose escalation, evaluation of intermediate doses, and expansion of an existing dose level are all permissible at the discretion of the investigator, if such measures are needed for patient safety or for a better understanding of the dose-related toxicity, exposure, or pharmacodynamics of minnelide.

Toxicity will be evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 4.0. Adverse events (AEs) will be assessed, and laboratory values, vital signs, and electrocardiograms (ECGs) will be obtained to evaluate the safety and tolerability of minnelide. Serial blood samples for determination of the plasma concentration of minnelide will be obtained during Cycle 1 at pre-specified time points. Assessment of disease response will follow the criteria outlined in the recommendations of the International Working Group (IWG) for diagnosis, standardization of response criteria, treatment outcomes, and reporting standards for therapeutic trials in myeloid malignancies \[21, 22\]. Circulating leukemic blasts will be assayed for pharmacodynamic marker levels before and at pre-defined time points after minnelide administration to characterize the extent and duration of the biological effects of minnelide in leukemic cells. Exploratory analyses of potential relationships between measures of plasma drug exposure and pharmacodynamic effects of minnelide may be performed as permitted by the data.

Minnelide in Adult Patients With Relapsed or Refractory Acute Myeloid Leukemia

A Phase I Pilot Study of Minnelide, A Novel Heat Shock Protein 70 Inhibitor, in Adult Patients With Relapsed or Refractory Acute Myeloid Leukemia

Rate of toxicity in study participants including serious adverse events (SAEs), grade 3 or higher adverse events (AEs), and dose limiting toxicities (DLTs) by treatment dose level cohorts. Toxicity will be assessed in terms of nature, grade and attribution to treatment, using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 4.03.

* Evaluable for Safety: Study participants who receive at least one dose of Minnelide therapy.
* Evaluable for DLT: Study participants who either experience a DLT during Cycle 1 or receive at least 12 (80%) of scheduled doses of minnelide during Cycle 1 without a DLT. Missed doses will not be made up. Eligible patients who discontinue minnelide therapy, miss more than 3 doses of Minnelide, or require a dose reduction in minnelide during Cycle 1 for reasons other than DLT will not be evaluable for DLT and will be replaced.

The MTD will be defined as highest dose level below or at the maximally administered dose for which ≤ 1 out of 6 patients experiences a dose-limiting toxicity (DLT). To determine the MTD of Minnelide, an approach using traditional "3+3" escalation rules will be used. Dose-limiting toxicity (DLT) will be defined as events that are considered by the investigator to be related to therapy with minnelide. Although DLTs may occur at any point during treatment, only DLTs occurring during Cycle 1 of treatment will influence decisions regarding dose escalation.

Following the proposed dose escalation and expansion cohort, the RP2D of Minnelide will be established as the highest dose level tested for which no more than 2 out of 12 patients experiences a dose-limiting toxicity.

Efficacy will be determined by overall response rate (ORR) to Minnelide therapy in study participants. Overall response rate includes rate of study participants experiencing complete response (CR), CR with incomplete bone marrow recovery (CRi); or Partial response (PR) to Minnelide therapy. Best response will be determined using serial blood and bone marrow sampling throughout the course of treatment. Responses will be documented according to revised/modified International Working Group (IWG) Response Criteria (Cheson et al. 2003 for AML and update 2010). Study participants who receive at least 1 cycle of protocol therapy, have measurable disease at baseline, and have at least one post-baseline disease assessment are evaluable for efficacy.

The area under the plasma concentration-time curve from time 0 to 24 hours post-dose (AUC24hr) will be assessed. Serial blood samples for the determination of plasma concentrations of Minnelide will be collected at pre-specified time points during Cycle 1 to characterize the PK of Minnelide. Plasma for measuring Minnelide concentrations will be collected on day 1 and 8 pre-dose, at the end of infusion (EOI), 0.5, 2, 4, 6, 24 hours post-dose. Descriptive statistics will be used to summarize Cmax for each dose level and all patients. Study participants who receive at least 1 dose of minnelide therapy and undergo at least 5 PK blood draws with concentration-time data to reliably estimate PK parameters are evaluable for PK.

Cmax is the maximum (or peak) plasma concentration that a drug achieves in a specified compartment or test area of the body after the drug has been administrated and before the administration of a second dose. Serial blood samples for the determination of plasma concentrations of Minnelide will be collected at pre-specified time points during Cycle 1 to characterize the PK of Minnelide. Plasma for measuring Minnelide concentrations will be collected on day 1 and 8 pre-dose, at the end of infusion (EOI), 0.5, 2, 4, 6, 24 hours post-dose. Descriptive statistics will be used to summarize Cmax for each dose level and all patients. Study participants who receive at least 1 dose of minnelide therapy and undergo at least 5 PK blood draws with concentration-time data to reliably estimate PK parameters are evaluable for PK.

Tmax is the time it takes a drug or other substance to reach the maximum concentration (Cmax). Serial blood samples for the determination of plasma concentrations of Minnelide will be collected at pre-specified time points during Cycle 1 to characterize the PK of Minnelide. Plasma for measuring Minnelide concentrations will be collected on day 1 and 8 pre-dose, at the end of infusion (EOI), 0.5, 2, 4, 6, 24 hours post-dose. Descriptive statistics will be used to summarize Tmax for each dose level and all patients. Study participants who receive at least 1 dose of minnelide therapy and undergo at least 5 PK blood draws with concentration-time data to reliably estimate PK parameters are evaluable for PK.

Terminal phase half-life (t1/2) will be assessed. Half-life (t1/2) is the amount of time it takes for the drug concentration in the plasma to decline by half. Serial blood samples for the determination of plasma concentrations of Minnelide will be collected at pre-specified time points during Cycle 1 to characterize the PK of Minnelide. Plasma for measuring Minnelide concentrations will be collected on day 1 and 8 pre-dose, at the end of infusion (EOI), 0.5, 2, 4, 6, 24 hours post-dose. Descriptive statistics will be used to summarize terminal phase half life for each dose level and all patients. Study participants who receive at least 1 dose of minnelide therapy and undergo at least 5 PK blood draws with concentration-time data to reliably estimate PK parameters are evaluable for PK.

Apparent total clearance of the drug from plasma, the rate at which a drug is removed from the body, considered as a single unit, the sum of renal clearance + hepatic clearance + other clearance, expressed as volume per unit time. Serial blood samples for the determination of plasma concentrations of Minnelide will be collected at pre-specified time points during Cycle 1 to characterize the PK of Minnelide. Plasma for measuring Minnelide concentrations will be collected on day 1 and 8 pre-dose, at the end of infusion (EOI), 0.5, 2, 4, 6, 24 hours post-dose. Descriptive statistics will be used to summarize terminal phase half life for each dose level and all patients. Study participants who receive at least 1 dose of minnelide therapy and undergo at least 5 PK blood draws with concentration-time data to reliably estimate PK parameters are evaluable for PK.

The apparent volume of distribution is the theoretical volume of fluid into which the total drug administered would have to be diluted to produce the concentration in plasma. Serial blood samples for the determination of plasma concentrations of Minnelide will be collected at pre-specified time points during Cycle 1 to characterize the PK of Minnelide. Plasma for measuring Minnelide concentrations will be collected on day 1 and 8 pre-dose, at the end of infusion (EOI), 0.5, 2, 4, 6, 24 hours post-dose. Descriptive statistics will be used to summarize terminal phase half life for each dose level and all patients. Study participants who receive at least 1 dose of minnelide therapy and undergo at least 5 PK blood draws with concentration-time data to reliably estimate PK parameters are evaluable for PK.

Pharmacodynamic (PD) measurements will be obtained from serial blood and bone marrow sampling at specified time points to describe the PD effects of Minnelide. PD paramaters include HSP70 expression and activity, mitochondrial cytochrome c, caspase-3 activation, PI3K/Akt/mTOR and MAPK/ERK pathway activity, and other relevant markers. Study participants who receive at least 1 dose of Minnelide and undergo at least 2 PD blood and bone marrow samples are evaluable. Descriptive statistics will be used to summarize PD parameters for each dose level and all patients.

* Blood - PD Sampling at pre-dose Cycle 1 Day 1, Day 2 and Day 8; at investigator discretion afterwards on Day 1 of each/every other cycle , and End of Study visit; assessed up to 12 months
* Marrow - PD Sampling at pre-dose Cycle 1 Day 1, Cycle 2 Day 1; at investigator discretion afterwards and End of Study visit; assessed up to 12 months

Justin Watts

Assistant Professor of Medicine

Tin Fluorides

A 3+3 design will be used. The first 3 patients will be treated at dose level 1. If none experience a Dose Limiting Toxicity (DLT), the next 3 patients will be treated at dose level 2. If a DLT is observed in 1 out of 3 patients at dose level 1, up to an 3 more patients will be enrolled and treated at that dose level. If 2 patients at dose level have DLTs, dosing will be lowered to dose level -1 (.5 mg daily, taken orally). If 2 or more of the up to 6 patients at any dose level have DLTs, the preceding dose will be declared the Maximum Tolerated Dose (MTD). If more than 1 DLT occurs at Dose Level -1, the investigators will consider stopping the study. Once the MTD has been established, an additional 10 patients will be enrolled at this level to better characterize safety and tolerability.

Patients will take Minnelide orally once daily on Days 1-21 of 28 day Cycle. Dose Escalation Schedule: Dose Level -1: .5 mg, Dose Level 1: .75 mg, Dose Level 2: 1 mg, Dose Level 3: 1.25 mg.

Zhuoer Xie, MD

This study is to determine the safety and recommended dosing of Minnelide in Acute Myeloid Leukemia (AML)

This phase 1 dose escalation clinical trial will establish the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of Minnelide as single-agent in relapsed/refractory (R/R) acute myeloid leukemia (AML) patients who are ineligible to receive intensive chemotherapy. The oral formulation of Minnelide will be used. Minnelide is a prodrug of triptolide (a potent heat shock protein (HSP) 70 inhibitor) with promising preclinical activity in AML.

Dose Escalation Study of Minnelide in Relapsed or Refractory Acute Myeloid Leukemia

Phase 1/1b Dose Escalation Study of Minnelide in Relapsed or Refractory Acute Myeloid Leukemia

MTD will be determined by testing increasing doses up to 1.25 mg daily. MTD reflects highest dose of drug that did not cause a Dose Limiting Toxicity (DLT).

A DLT is any Grade 3 or 4 drug-related non-hematologic toxicity, with some exceptions per protocol.

Participants who experience Complete Response (CR) and Complete Response with Incomplete Blood Count Recovery (CRi) rate as defined by 2003 International Working Group (IWG) for AML.

Overall Response Rate is defined as CR + CRi + partial response (PR) as defined by 2003 IWG criteria for AML.

RFS is defined as time interval between achievement of CR to time of relapse.

OS defined as time interval from time of enrollment onto the clinical trial to death from any cause.

H. Lee Moffitt Cancer Center and Research Institute

Adenocarcinoma

Carcinoma

Neoplasms, Glandular and Epithelial

Gastrointestinal Agents

Gemcitabine

Folfirinox

Pancrelipase

Pancreatin

This is an open-label, Phase 1b study of MinnelideTM given once a day on Days 1 to 5, Days 8 to12 and Days 15 to 19 in combination with SOC (nab-paclitaxel \[Abraxane\] plus gemcitabine). The study will be conducted in patients with disease progression while on FOLFIRINOX as first treatment and who have had no prior treatment with nab-paclitaxel (Abraxane) plus gemcitabine or single agent nab paclitaxel or gemcitabine or in any other combinations. The total number of treatment cycles administered will be dependent on drug tolerability by patient.

Stressing the patient's pancreatic cancer by giving the anti super-enhancer Minnelide to increase endoplasmic reticulum (ER) stress and improve the progression-free survival (PFS) when patients are treated with standard of care (SOC) nanoparticle albumin-bound (nab)-paclitaxel (Abraxane) plus gemcitabine.

Miae Jo, RN

Joon Oh Park, MD

A Phase 1b, Open-Label, Safety, Pharmacokinetic, and Pharmacodynamic Study of an Anti-super-enhancer Minnelide Once a Day on Days 1 to 5, Days 8 to 12 and Days 15 to 19 Along with Abraxane Plus Gemcitabine in Patients with Metastatic Adenocarcinoma of the Pancreas

Stressing the patient's pancreatic cancer by giving the anti-super-enhancer Minnelide to increase endoplasmic reticulum (ER) stress and improve the progression-free survival (PFS) when patients are treated with standard of care (SOC) nanoparticle albumin-bound (nab)-paclitaxel (Abraxane) plus gemcitabine.

Stressing the patient's pancreatic cancer by giving the anti super-enhancer MinnelideTM to increase endoplasmic reticulum (ER) stress and improve the progression-free survival (PFS) when patients are treated with standard of care (SOC) nanoparticle albumin-bound (nab)-paclitaxel (Abraxane) plus gemcitabine.

Minnelide Along With Abraxane Plus Gemcitabine in Patients With Metastatic Adenocarcinoma of the Pancreas

A Phase 1b, Open-Label, Safety, Pharmacokinetic, and Pharmacodynamic Study of an Anti-super-enhancer Minnelide Given Along With Abraxane Plus Gemcitabine in Patients With Metastatic Adenocarcinoma of the Pancreas

To observe any increase in the number of patients that experience Grade 4 neutropenia lasting ≥ 5 days or Grade 3 or 4 neutropenia with fever and/or infection; Grade 4 thrombocytopenia (or Grade 3 with bleeding); Grade 3 or 4 treatment-related non-hematological toxicity (Grade 3 nausea, vomiting or diarrhea that last \> 72 hours despite maximal treatment when Minnelide is given in combination of gemcitabine and nab-paclitaxel compared to the incidence with gemcitabine and nab-paclitaxel.

To determine the pharmacokinetics of Minnelide when given in combination with gemcitabine and nab-paclitaxel

Plasma concentration data will be used to determine the following PK parameters:

* AUC Area under the concentration curve
* Cmax Maximum plasma concentration
* Tmax Time to maximum plasma concentration
* t1/2 Terminal phase half life
* CL/F Total body clearance
* Vd/F Apparent volume of distribution
* To determine the effects of Minnelide on the pharmacodynamics of GRP78

Carcinoma, Adenosquamous

Reproductive Control Agents

Triptolide

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

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

NCI Medical Oncology Referral Office

Christine C Alewine, M.D.

For more information at the NIH Clinical Center contact National Cancer Institute Referral Office

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.

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

A Phase II Trial of the Superenhancer Inhibitor Minnelide in Advanced Refractory Adenosquamous Carcinoma of the Pancreas (ASCP)

.All IPD recorded in the medical record will be shared with intramural investigators upon request.@@@@@@In addition, all large scale genomic sequencing data will be shared with subscribers to dbGaP.

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

The length of time from the start of treatment that patients diagnosed with the disease are still alive.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Minnelide™ Capsules Alone and in Combination With Paclitaxel in Advanced Gastric Cancer	NCT05566834	Gastric Cancer	Minnelide	19 Years -	Minneamrita Therapeutics LLC
A Phase II, International Open Label Trial of Minnelide™ in Patients With Refractory Pancreatic Cancer	NCT03117920	Pancreatic Canc...	Minnelide	18 Years -	Minneamrita Therapeutics LLC
Minnelide in Adult Patients With Relapsed or Refractory Acute Myeloid Leukemia	NCT03347994	Acute Myeloid L...	Minnelide	18 Years -	University of Miami
Dose Escalation Study of Minnelide in Relapsed or Refractory Acute Myeloid Leukemia	NCT03760523	Acute Myeloid L...	Minnelide	18 Years -	H. Lee Moffitt Cancer Center and Research Institute
A Phase II, International Open Label Trial of Minnelide™ in Patients With Refractory Pancreatic Cancer	NCT03117920	Pancreatic Canc...	Minnelide	18 Years -	Minneamrita Therapeutics LLC
Minnelide Along With Abraxane Plus Gemcitabine in Patients With Metastatic Adenocarcinoma of the Pancreas	NCT05557851	Metastatic Aden...	Minnelide	19 Years -	Minneamrita Therapeutics LLC
Minnelide in Adult Patients With Relapsed or Refractory Acute Myeloid Leukemia	NCT03347994	Acute Myeloid L...	Minnelide	18 Years -	University of Miami
Superenhancer Inhibitor Minnelide in Advanced Refractory Adenosquamous Carcinoma of the Pancreas (ASCP)	NCT04896073	Adenosquamous C...	Minnelide	18 Years -	National Institutes of Health Clinical Center (CC)

Spots Global Cancer Trial Database for minnelide

Every month we try and update this database with for minnelide cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for minnelide

Every month we try and update this database with for minnelide cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for minnelide cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.