Neoplasms

All Conditions

Digestive System Diseases

Rare Diseases

Neuroendocrine Tumors

Gastrointestinal Neoplasms

Digestive System Neoplasms

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Gastrointestinal Diseases

Neuroendocrine Tumor

Gastro-enteropancreatic Neuroendocrine Tumor

Neuroepithelioma

Platelet Aggregation Inhibitors

All Drugs and Chemicals

Resveratrol

Antioxidants

Protective Agents

Enzyme Inhibitors

5 gm/day of resveratrol orally, in two divided doses of 2.5 gm each without a break in therapy for a total of three cycles.

Emily R. Winslow, MD

Resveratrol has been shown to activate a protein called Notch-1. Signaling of Notch-1 has been shown to prevent tumor cell growth. Resveratrol has also been shown to prevent growth of tumors in mice. The purpose of this study is to examine the effects of resveratrol and Notch-1 on neuroendocrine tumor tissue and to examine how people with neuroendocrine tumors who take resveratrol for up to three months tolerate the product.

Patients will be treated with a dose of 5 gm/day of resveratrol orally, in two divided doses of 2.5 gm each without a break in therapy for a total of three cycles. All patients who receive at least one dose of resveratrol will be evaluated for toxicity and tolerability. Toxicities will be assessed every 28 days while the study drug is being taken by the patient. Pill bottles will be reviewed at this visit as well to ensure compliance with the study medication. Toxicities will be graded according to the NCI Common Toxicity Criteria. Blood will be drawn for a complete blood count and comprehensive metabolic panel. In addition, one vial of serum will be stored at the time of each toxicity assessment for later analysis of resveratrol levels. This level must be drawn one hour after the morning dose and the participants will be instructed to alter the time of the morning dose so as to allow proper timing with the scheduled blood draw.

During the third cycle of treatment, a post-treatment biopsy will be obtained for study related purposes and will be processed only for research related purposes.

A Biological Study of Resveratrol's Effects on Notch-1 Signaling in Subjects With Low Grade Gastrointestinal Tumors

1. The investigators aim primarily to show that resveratrol therapy in patients with low-grade GI neuroendocrine tumors will significantly increase Notch1 activation in post-treatment tumor biopsy specimens when compared to pretreatment levels.

Endpoints: The primary endpoint will be the level of expression of full length Notch1, cleaved Notch1, HES-1, and ASCL-1, as measured by Western blot using quantitative densitometry. The pre-treatment and post-treatment biopsies will be processed and analyzed simultaneously so as to minimize inter-test variability.

Frequency of grade three or greater toxicities as defined by the NCI Common Toxicity Criteria.

The level of tumor markers (eg, chromogranin, 5-HIAA, gastrin, and others) pre-treatment will be compared to the post-treatment levels (collected every three months) as a measure of tumor response. In addition, serial axial imaging will be used to document tumor response rates according to standard Response Evaluation Criteria in Solid Tumors (RECIST).

University of Wisconsin, Madison

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Carcinoma

Carcinoma, Neuroendocrine

Adenocarcinoma

Prostatic Neoplasms

Carcinoma, Adenosquamous

Carcinoma, Islet Cell

Neoplasms, Glandular and Epithelial

Pancreatic Neoplasms

Endocrine Gland Neoplasms

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Neuroendocrine Tumor

Pancreatic Cancer

Pancreatic or gastrointestinal neuroendocrine neoplasms with Ki-67 \> 20%

Neuroendocrine prostate carcinoma with Ki-67 \> 20%

160 mg, PO, Once daily 5 days on and 2 days off

ESK981

Cancer AnswerLine

Vaibhav Sahai, MBBS, MS

Vaibhav Sahai

This protocol will enroll patients with pancreatic adenocarcinoma and adenosquamous carcinoma (Cohort 1), gastrointestinal/pancreatic neuroendocrine neoplasms with Ki-67 \> 20% (Cohort 2) and neuroendocrine prostate carcinoma (Cohort 3)). Each cohort will have its own interim analysis after enrollment of 10 patients.

Subjects will be given a one-month (28 day) supply of study drug (ESK981). Subjects will be instructed to take 4 capsules, with or without food, once per day for 5 consecutive calendar days, then take a drug holiday for 2 consecutive days before repeating the 5 days on-2 days off cycle in sets of 4 weeks or 28 calendar days. Subjects will be asked to keep a pill diary noting the date they take their study drug.

Multicenter Trial of ESK981 in Patients With Select Solid Tumors

A Phase II Multicenter Trial of ESK981 in Patients With Select Solid Tumors

Determining efficacy using proportion of patients alive and progression-free at 4 months within each cancer subtype

The ORR will be assessed per RECIST v1.1 criteria (Cohort 1 and 2) or combined RECIST v1.1 + PCWG3 criteria (Cohort 3). Partial or complete response will require confirmation on repeat scan at least 4 weeks from initial radiologic response

DoR will be measured from the start date of the best response achieved until the date of relapse (i.e., progression). Continuing responders will be right-censored as of the most recent date on which their response status had been assessed. DoR applies to only the patients who achieve either a complete response or a partial response.

The OS will be defined from the date of treatment to either date of death or censoring and estimated using the product-limit method of Kaplan and Meier. Follow-up time will be censored at the date of last disease evaluation.

Adverse events (AEs) will be defined per the NCI Common Toxicity Criteria for Adverse Events (CTCAE) v5.0.

The PFS will be defined as time from date of initial treatment to date of radiological or clinical progression (leading to withdrawal from the study treatment), or death from any cause on study treatment, whichever comes first. Follow-up time will be censored at the date of last disease evaluation.

University of Michigan Rogel Cancer Center

Skin and Connective Tissue Diseases

Symptoms and General Pathology

Breast Neoplasms

Melanoma

Neoplasm, Residual

Patients with early stage or locally advanced disease that is planned for or have undergone curative treatment will have next-generation sequencing (NGS)-based ctDNA analysis performed on blood samples to determine minimal residual disease (MRD). Blood samples, stool samples, and additional archival/fresh tumor specimens will be collected for banking and future research purposes.

Celeste Yu, MSc

Elizabeth Shah

Celeste Yu

Lillian Siu, MD

Philippe Bedard, MD

Patients who have undergone curative treatment may be at risk of relapse. This study will collect, annotate, and sequence biospecimens (blood, stool, and tissue) from patients across different tumor types to detect molecular residual disease (MRD) before metastases become radiographically or clinically detectable. This will allow for early cancer interception, and hopefully prolong relapse-free survival across tumor types.

The development of anticancer drugs typically starts with patients with advanced cancers who have exhausted standard treatments. Yet even the most active new drugs produce only modest benefits in patients with advanced cancers because of the emergence of resistance, similar to the resistance that bacteria develop when they are repeatedly exposed to antibiotics. In order to achieve larger magnitude gains in survival and make greater impact in the field of cancer, promising drugs must be tested in patients with curable malignancies who have undergone definitive treatment but are at high risk of relapse. Interception is the active intervention of cancers at an early stage, offering an opportunity to eliminate molecular residual disease (MRD) before clinical relapse. MRD describes the situation in which cancer-derived biomarkers are detectable, typically using highly sensitive and specific molecular assays in blood or other body substances that are below the threshold of detection by conventional tests such as CT scans or radiological imaging. Using innovative technologies to monitor patients at high risk of relapse, and applying them to serial samples of their circulating tumor DNA, other body fluids, stool and radiological images, the goal is to develop AI-based models to identify those who are at the highest risk of relapse. This will allow interception studies to be conducted to target microscopic tumor cells in these patients to increase cancer cure rates.

Archival/fresh tumor tissue, blood samples, stool samples

Non-Invasive Artificial Intelligence-Based Platform MonIToring Program (NIP IT!)

De-identified study data (including genetic data) may be potentially shared with approved research collaborators.

Next-generation sequencing based ctDNA analysis

Princess Margaret Hospital, Canada

University Health Network, Toronto

Intestinal Neoplasms

Stomach Neoplasms

Intestinal Diseases

Stomach Diseases

Stomach Cancer

Antineoplastic Agents

Irinotecan

Etoposide

Cisplatin

Etoposide phosphate

Topoisomerase I Inhibitors

Etoposide 100mg/m\^2 ivggt on days 1, 2, 3, Cisplatin 25mg/m\^2 ivggt on days 1, 2, 3, repeated every 21 days. When the investigator believes that the participant is not suitable for continued medication or the evaluation is progressive disease (PD) according to the RECIST 1.1 standard, the medication is over.

Irinotecan 65 mg/m\^2 ivggt on days 1, 8, Cisplatin 30 mg/m\^2 ivggt on days 1, 8, repeated every 21 days. When the investigator believes that the participant is not suitable for continued medication or the evaluation is progressive disease (PD) according to the RECIST 1.1 standard, the medication is over.

Etoposide 100mg/m\^2 ivggt on days 1, 2, 3, Cisplatin 25mg/m\^2 ivggt on days 1, 2, 3, repeated every 21 days.

Irinotecan 65 mg/m\^2 ivggt on days 1, 8, Cisplatin 30 mg/m\^2 ivggt on days 1, 8, repeated every 21 days.

Ying Liu

Baoxia He

The aim of this study is to investigate the efficacy, safety, and survival benefit of etoposide plus cisplatin and irinotecan plus cisplatin in first-line therapy of non-primary pancreatic metastatic and/or unresectable gastrointestinal neuroendocrine tumor G3 type. In addition, the investigators will explore the resistance mechanisms of gastrointestinal neuroendocrine tumor G3, and screen out biomarkers that can predict the efficacy of chemotherapy.

The prognosis of gastrointestinal neuroendocrine tumor G3 type patients who cannot be surgically resected is poor. The median overall survival (OS) is only 6-10 months, and the 3-year survival rate is less than 10%. Among the neuroendocrine tumors of the digestive system, only pancreatic neuroendocrine tumor has a standard treatment strategy, and there is a lack of prospective clinical research data on other gastrointestinal neuroendocrine tumors. According to the chemotherapy regimen of small cell lung cancer, etoposide plus cisplatin or irinotecan plus cisplatin is the choice of rescue therapy for advanced non-surgical or metastatic neuroendocrine tumor G3 type. However, prospective studies are needed to confirm whether there are differences in efficacy and safety between the two chemotherapy regimens. The aim of this study is to investigate the efficacy, safety, and survival benefit of etoposide plus cisplatin and irinotecan plus cisplatin in first-line therapy of non-primary pancreatic metastatic and/or unresectable gastrointestinal neuroendocrine tumor G3 type. In addition, the investigators will explore the resistance mechanisms of gastrointestinal neuroendocrine tumor G3, and screen out biomarkers that can predict the efficacy of chemotherapy.

Etoposide/Cisplatin Compared With Irinotecan/Cisplatin for Advanced Gastrointestinal Neuroendocrine Tumor G3 Type

Phase II Trial of Etoposide Plus Cisplatin Compared With Irinotecan Plus Cisplatin for First-line Treatment of Non-primary Pancreatic Metastatic and/or Unresectable Gastrointestinal Neuroendocrine Tumor G3 Type

To compare objective response rate of the two arms from date of anti-cancer therapy until progression

From the first day of treatment until the date of first documented progression or date of death from any cause

From the first day of treatment to death or last survival confirm date

Treatment-related adverse events will be assessed by CT CAE v4.0

Quality of Life Questionnaire (QLQ-C30) will be evaluated since treatment begins. At the end of the trail, the differences between the two indicators will be compared with Mixed-effects model repeated measures (MMRM), where the baseline is scored as a covariant and the treatment group as a fixed variable. In addition, the baseline values of the two scores, the value of each visit, and the change value of the baseline will be statistically described.

Henan Cancer Hospital

Adenoma

Adenoma, Islet Cell

Anti-Infective Agents

Gastrointestinal Agents

Sirolimus

Pancrelipase

Pancreatin

Temsirolimus

MTOR Inhibitors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Clotrimazole

Miconazole

Antifungal Agents

Immunosuppressive Agents

Immunologic Factors

Patients with well-differentiated neuroendocrine tumors of the gastrointestinal tract, lung, or pancreas.

Prospective phase 2 single arm, open-label, multi-institutional study to determine the efficacy and safety prospective of nab-sirolimus administered by IV infusion

nab-sirolimus

Aadi Bioscience Medical Information

Jason Ledesma

Michael Demeure, MD

Jennifer Hedge

Allen Cohn, MD

Christine Terraciano

Scott Paulson, MD

Alexandria Phan, MD

Willis Navarro, MD

A Phase 2 multi-center, open-label, single arm study of nab-sirolimus in patients with well-differentiated neuroendocrine tumors (NETs) of the gastrointestinal tract, lung, or pancreas who have not received prior treatment with mTOR inhibitors

This is a prospective phase 2 single arm, open-label, multi-institutional study to determine the efficacy and safety prospective of nab-sirolimus and patients with functional or non-functional, well-differentiated, locally advanced unresectable in metastatic NETs of the GI tract, lung, or pancreas.

Trial of Nab-sirolimus in Patients With Well-differentiated Neuroendocrine Tumors (NETs) of the Gastrointestinal Tract, Lung, or Pancreas Who Have Not Received Prior Treatment With mTOR Inhibitors

A Phase 2 Multi-center, Open-label, Single Arm Study of Nab-sirolimus in Patients With Well-differentiated Neuroendocrine Tumors (NETs) of the Gastrointestinal Tract, Lung, or Pancreas Who Have Not Received Prior Treatment With mTOR Inhibitors

Objective Response Rate (ORR), defined as the proportion of patients with best overall response (BOR) of confirmed partial response (PR) or complete response (CR) from the time of study treatment initiation until progression of disease (PD) as determined by the Investigator using RECIST v1.1

Incidence and severity of treatment-emergent and treatment-related adverse events (AEs) as assessed by NCI CTCAE v5.0

Determined for patients with BOR of confirmed CR or PR defined as time from scan first showing response by RECIST v1.1 to PD or death

BOR of confirmed CR or PR (either of any duration) or stable disease (SD) ≥12 weeks by RECISTv1.1 following study treatment initiation

Time from first dose of study medication to initial measurement of CR or PR, where CR or PR is subsequently confirmed by RECIST v1.1

Number of months from study treatment initiation to the date of disease progression or death due to any cause

Number of months from study treatment initiation to the date of death due to any cause

Aadi Bioscience, Inc.

Colorectal Neoplasms

Carcinoma, Hepatocellular

Fibromatosis, Aggressive

Adrenocortical Carcinoma

Colonic Diseases

Rectal Diseases

Desmoid Tumor

Small Intestine Cancer

Participants will receive E7386 10, 15, 20 mg (milligram) or more, tablets, orally, twice daily, in 28-days treatment cycle until disease progression (PD), development of unacceptable toxicity, participant's request to discontinue, withdrawal of consent, or termination of the study program. Dose escalation of E7386 will be based on the available safety data from the previous cohorts.

Participants will receive E7386, tablets, orally, twice daily in 28-days treatment cycle until PD, development of unacceptable toxicity, participant's request to discontinue, withdrawal of consent, or termination of the study program. The highest dose of E7386 which is deemed tolerable, or the optimal dose based on PK or PD analysis in dose escalation part will be used for Expansion Part 1.

Participants will receive E7386, tablets, orally, twice daily in 28-days treatment cycle until PD, development of unacceptable toxicity, participant's request to discontinue, withdrawal of consent, or termination of the study program. The dose of Expansion Part 2 will be based on the available safety data from Dose Escalation and Expansion Part 1 of the study.

E7386

The primary objective of this study is to assess the safety and tolerability of E7386 in participants with solid tumor including CRC.

The study will be conducted in 3 parts: dose escalation part, expansion part 1 and expansion part 2. The study will include Pre-treatment Phase, Treatment Phase, and Extension Phase (in expansion parts only).

Eligible participants from Pre-Treatment Phase (screening period) will enter into the Treatment Phase to receive E7386. After Treatment Phase, participants will be followed in follow-up period of Extension Phase (in expansion parts only).

A Study of E7386 in Participants With Advanced Solid Tumor Including Colorectal Cancer (CRC)

An Open-label Phase 1 Study of E7386 in Subjects With Advanced Solid Tumor Including Colorectal Cancer

Eisai's data sharing commitment and further information on how to request data can be found on our website http://eisaiclinicaltrials.com/.

DLT will be defined as any of the events that are considered by the investigator to be at least possibly related to therapy with the study medication. Toxicity will be evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE 5.0).

BOR is defined as complete response (CR), partial response (PR), stable disease (SD), PD, and not evaluable (NE), where SD has to be achieved at greater than or equal to (\>=) 7 weeks after the first dose. The BOR will be assessed by investigator based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

The ORR is defined as the percentage of participants with a BOR of CR or PR. The ORR will be assessed by investigator based on RECIST version 1.1.

DCR is defined as the percentage of participants with a BOR of CR, PR, or SD. The DCR will be assessed by investigator based on RECIST version 1.1.

The CBR is defined as the percentage of participants with a BOR of CR, PR, or durable SD (duration of SD \>=23 weeks). The CBR will be assessed by investigator based on RECIST version 1.1.

PFS is defined as the time from the date of the first dose to the date of the first documentation of confirmed PD or death, whichever occurs first.

DOR is defined as the time from the first date of documented CR or PR to the date of PD or death, whichever occurs first. It will be calculated for participants whose BOR is CR or PR. DOR will be assessed according to RECIST version 1.1.

OS is defined as the time from the date of first dose to the date of death.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Biological Study of Resveratrol's Effects on Notch-1 Signaling in Subjects With Low Grade Gastrointestinal Tumors	NCT01476592	Neuroendocrine ...	Resveratrol	18 Years -	University of Wisconsin, Madison
Multicenter Trial of ESK981 in Patients With Select Solid Tumors	NCT05988918	Pancreatic Aden... Adenosquamous C... Pancreatic Neur... Pancreatic Neur... Gastrointestina... Gastrointestina... Neuroendocrine ...	ESK981	18 Years -	University of Michigan Rogel Cancer Center
Non-Invasive Artificial Intelligence-Based Platform MonIToring Program (NIP IT!)	NCT05196087	Breast Cancer Melanoma Gastrointestina...		18 Years -	University Health Network, Toronto
A Biological Study of Resveratrol's Effects on Notch-1 Signaling in Subjects With Low Grade Gastrointestinal Tumors	NCT01476592	Neuroendocrine ...	Resveratrol	18 Years -	University of Wisconsin, Madison
Non-Invasive Artificial Intelligence-Based Platform MonIToring Program (NIP IT!)	NCT05196087	Breast Cancer Melanoma Gastrointestina...		18 Years -	University Health Network, Toronto
Etoposide/Cisplatin Compared With Irinotecan/Cisplatin for Advanced Gastrointestinal Neuroendocrine Tumor G3 Type	NCT03963193	Gastrointestina...	Etoposide Irinotecan	18 Years - 75 Years	Henan Cancer Hospital
Trial of Nab-sirolimus in Patients With Well-differentiated Neuroendocrine Tumors (NETs) of the Gastrointestinal Tract, Lung, or Pancreas Who Have Not Received Prior Treatment With mTOR Inhibitors	NCT05997056	Neuroendocrine ... NET Pancreatic Neur... Gastrointestina... Pulmonary Neuro...	nab-sirolimus	18 Years -	Aadi Bioscience, Inc.
A Study of E7386 in Participants With Advanced Solid Tumor Including Colorectal Cancer (CRC)	NCT03833700	Solid Neoplasms Colorectal Neop... Gastrointestina...	E7386	18 Years -	Eisai Inc.

Spots Global Cancer Trial Database for gastrointestinal neuroendocrine tumor