9-ING-41 in Patients with Advanced Cancers

NCT ID: NCT03678883

Last Updated: 2024-11-07

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

350 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-01-04

Study Completion Date

2026-01-31

Brief Summary

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GSK-3β is a potentially important therapeutic target in human malignancies. The Actuate 1801 Phase 1/2 study is designed to evaluate the safety and efficacy of 9-ING-41, a potent GSK-3β inhibitor, as a single agent and in combination with cytotoxic agents, in patients with refractory cancers.

Detailed Description

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9-ING-41 is a first-in-class, intravenously administered, maleimide-based small molecule potent selective GSK-3β inhibitor with significant pre-clinical antitumor activity. GSK-3 is a serine/threonine kinase initially described as a key regulator of metabolism and has a role in diverse disease processes including cancer, immune disorders, pathologic fibrosis, metabolic disorders, and neurological disorders. GSK-3 has two ubiquitously expressed and highly conserved isoforms, GSK-3α and GSK-3β, with both shared and distinct substrates and functional effects. GSK-3β is particularly important in tumor progression and modulation of oncogenes (including beta-catenin, cyclin D1 and c-Myc), cell cycle regulators (e.g. p27Kip1) and mediators of epithelial-mesenchymal transition (e.g. zinc finger protein SNAI1, Snail). Aberrant overexpression of GSK-3β has been shown to promote tumor growth and chemotherapy resistance in various solid tumors including colon, ovarian, and pancreatic cancers and glioblastoma through differential effects on the pro-survival nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and c-Myc pathways as well on tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and p53-mediated apoptotic mechanisms. GSK-3β helps maintain malignant cell survival and proliferation, particularly in terms of mediating resistance to standard anti-cancer therapies, through the NF-κB pathway. GSK-3β has been established as a potential anticancer target in human bladder, breast, colorectal, glioblastoma, lung, neuroblastoma, ovarian, pancreatic, prostate, renal and thyroid cancers as well as chronic lymphocytic leukemia and lymphomas.

9-ING-41 is a small molecule potent selective GSK-3β inhibitor with broad spectrum pre-clinical antitumor activity. It's modes of action include downregulation of NF-κB and decreasing the expression NF-κB target genes including cyclin D1, Bcl-2, anti-apoptotic protein (XIAP) and B-cell lymphoma-extra large (Bcl-XL) leading to inhibition of tumor growth in multiple solid tumor cell and lymphoma lines and patient derived xenograft (PDX) models. NF-κB is constitutively active in cancer cells and promotes anti-apoptotic molecule expression. NF-κB activation is particularly important in cancer cells that have become chemo- and/or radio-resistant. 9-ING-41 also has significant activity in pre-clinical models of pathological pleural and pulmonary fibrosis. 9-ING-41 has significant in vitro and in vivo activity as a single agent and/or in combination with standard cytotoxic chemotherapies in a spectrum of solid tumors and hematological malignancies including bladder, breast, glioblastoma, neuroblastoma, pancreatic, sarcomas, and renal cancers as well as lymphomas.

The 1801 had three parts:

* Completed: Part 1 (9-ING-41 as monotherapy): The standard 3+3 dose escalation design will be applied to all dose cohorts until the Maximum Tolerated Dose (MTD) or Recommended Phase 2 Dose (RP2D) is identified.
* Completed: 9-ING-41 combined with standard anticancer agents: The 3+3 dose escalation study design will be used for 8 chemotherapy combination regimens (9-ING-41 plus gemcitabine, doxorubicin, lomustine, carboplatin, irinotecan, nab-paclitaxel plus gemcitabine, paclitaxel plus carboplatin, pemetrexed plus carboplatin) to identify the MTD/RP2D of each regimen.
* Part 3: A randomized Phase 2 study of 9-ING-41 either once or twice weekly with gemcitabine and nab-paclitaxel (GA) versus GA alone for patients with previously untreated metastatic or locally advanced pancreatic cancer is now open.

Conditions

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Cancer Pancreatic Cancer Sarcoma Renal Cancer Refractory Cancer Refractory Neoplasm Refractory Non-Hodgkin Lymphoma Pancreatic Adenocarcinoma Resistant Cancer Neoplasm Metastasis Neoplasm of Bone Neoplasm, Breast Neoplasm of Lung Neoplasms,Colorectal Neoplasms Pancreatic Malignant Glioma Malignancies Malignancies Multiple Bone Metastases Bone Neoplasm Bone Cancer Pancreas Cancer Pancreatic Neoplasms Breast Neoplasms Acute T Cell Leukemia Lymphoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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9-ING-41

Drug: 9-ING-41

Group Type EXPERIMENTAL

9-ING-41

Intervention Type DRUG

Starting dose of-9-ING-41 will be administered on Day 1 and 4 each week of a 21-day cycle. 9-ING-41 will be administered intravenously over 60 minutes.

9-ING-41 plus Gemcitabine

Drugs: Gemcitabine - 21 day cycle. 9-ING-41

Group Type EXPERIMENTAL

9-ING-41

Intervention Type DRUG

Starting dose of-9-ING-41 will be administered on Day 1 and 4 each week of a 21-day cycle. 9-ING-41 will be administered intravenously over 60 minutes.

Gemcitabine - 21 day cycle

Intervention Type DRUG

Gemcitabine 1250 mg/m2 as a 30-minute intravenous infusion on Days 1 and 8 of a 21-day cycle

9-ING-41 plus Doxorubicin

Drugs: Doxorubicin. 9-ING-41

Group Type EXPERIMENTAL

9-ING-41

Intervention Type DRUG

Starting dose of-9-ING-41 will be administered on Day 1 and 4 each week of a 21-day cycle. 9-ING-41 will be administered intravenously over 60 minutes.

Doxorubicin.

Intervention Type DRUG

Doxorubicin 75 mg/m2, intravenous bolus on Day 1 of a 21-day cycle up to a maximum lifetime dose of 550 mg/m2.

9-ING-41 plus Lomustine

Drugs: Lomustine. 9-ING-41.

Group Type EXPERIMENTAL

9-ING-41

Intervention Type DRUG

Starting dose of-9-ING-41 will be administered on Day 1 and 4 each week of a 21-day cycle. 9-ING-41 will be administered intravenously over 60 minutes.

Lomustine

Intervention Type DRUG

Lomustine 30 mg/m² orally as a single dose, weekly for twelve weeks.

9-ING-41 plus Carboplatin

Drugs: Carboplatin. 9-ING-41.

Group Type EXPERIMENTAL

9-ING-41

Intervention Type DRUG

Starting dose of-9-ING-41 will be administered on Day 1 and 4 each week of a 21-day cycle. 9-ING-41 will be administered intravenously over 60 minutes.

Carboplatin.

Intervention Type DRUG

Carboplatin AUC 6 IV over 1 hour on Day 1 of a 21-day cycle.

9-ING-41 plus nab paclitaxel Gemcitabine

Drugs: Nab-paclitaxel. Gemcitabine - 28 day cycle. 9-ING-41.

Group Type EXPERIMENTAL

9-ING-41

Intervention Type DRUG

Starting dose of-9-ING-41 will be administered on Day 1 and 4 each week of a 21-day cycle. 9-ING-41 will be administered intravenously over 60 minutes.

Nab paclitaxel.

Intervention Type DRUG

Nab-paclitaxel 125 mg/m2 intravenously on Days 1, 8 and 15 of a 28-day cycle

Gemcitabine - 28 day cycle

Intervention Type DRUG

Gemcitabine 1000 mg/m2 intravenously over 30-minutes on Days 1, 8 and 15 of a 28-day cycle

9-ING-41 plus Paclitaxel/Carboplatin

Drugs: Paclitaxel. Carboplatin. 9-ING-41.

Group Type EXPERIMENTAL

9-ING-41

Intervention Type DRUG

Starting dose of-9-ING-41 will be administered on Day 1 and 4 each week of a 21-day cycle. 9-ING-41 will be administered intravenously over 60 minutes.

Carboplatin.

Intervention Type DRUG

Carboplatin AUC 6 IV over 1 hour on Day 1 of a 21-day cycle.

Paclitaxel.

Intervention Type DRUG

Paclitaxel 175 mg/m2 intravenously over 3 hours on Day 1 of a 21-day cycle.

9-ING-41 plus Irinotecan

Drugs: Irinotecan. 9-ING-41.

Group Type EXPERIMENTAL

9-ING-41

Intervention Type DRUG

Starting dose of-9-ING-41 will be administered on Day 1 and 4 each week of a 21-day cycle. 9-ING-41 will be administered intravenously over 60 minutes.

Irinotecan

Intervention Type DRUG

Irinotecan 350 mg/m2 intravenously over 90-minutes on Day 1 of a 21-day cycle

Interventions

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9-ING-41

Starting dose of-9-ING-41 will be administered on Day 1 and 4 each week of a 21-day cycle. 9-ING-41 will be administered intravenously over 60 minutes.

Intervention Type DRUG

Gemcitabine - 21 day cycle

Gemcitabine 1250 mg/m2 as a 30-minute intravenous infusion on Days 1 and 8 of a 21-day cycle

Intervention Type DRUG

Doxorubicin.

Doxorubicin 75 mg/m2, intravenous bolus on Day 1 of a 21-day cycle up to a maximum lifetime dose of 550 mg/m2.

Intervention Type DRUG

Lomustine

Lomustine 30 mg/m² orally as a single dose, weekly for twelve weeks.

Intervention Type DRUG

Carboplatin.

Carboplatin AUC 6 IV over 1 hour on Day 1 of a 21-day cycle.

Intervention Type DRUG

Nab paclitaxel.

Nab-paclitaxel 125 mg/m2 intravenously on Days 1, 8 and 15 of a 28-day cycle

Intervention Type DRUG

Paclitaxel.

Paclitaxel 175 mg/m2 intravenously over 3 hours on Day 1 of a 21-day cycle.

Intervention Type DRUG

Gemcitabine - 28 day cycle

Gemcitabine 1000 mg/m2 intravenously over 30-minutes on Days 1, 8 and 15 of a 28-day cycle

Intervention Type DRUG

Irinotecan

Irinotecan 350 mg/m2 intravenously over 90-minutes on Day 1 of a 21-day cycle

Intervention Type DRUG

Other Intervention Names

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Gemzar Doxil Adriamycin CCNU Gleostine Paraplatin Abraxane Protein-bound paclitaxel Nanoparticle albumin-bound paclitaxel Taxol Gemzar Camptosar

Eligibility Criteria

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Inclusion Criteria

* Patient -

1. Is able to understand and voluntarily sign a written informed consent and is willing and able to comply with the protocol requirements including scheduled visits, treatment plan, laboratory tests and other study procedures.
2. Is aged ≥ 18 years
3. Has pathologically confirmed advanced or metastatic malignancy characterized by one or more of the following:

1. Patient is intolerant of existing therapy(ies) known to provide clinical benefit for their condition
2. Malignancy is refractory to existing therapy(ies) known to potentially provide clinical benefit
3. Malignancy has relapsed after standard therapy
4. Malignancy for which there is no standard therapy that improves survival by at least 3 months
4. Has evaluable tumor(s) by standard radiological and/or laboratory assessments as applicable to their malignancy - in Part 3, patients with solid tumors must have least 1 measurable lesion per response evaluation criteria in solid tumors (RECIST) v1.1 criteria, measured preferably by computed tomography (CT) scan or magnetic resonance image (MRI). In the case of patients with glioblastoma multiforme (GBM) or other central nervous system (CNS) tumors, the tumor must be measurable, defined as a clearly enhancing tumor with at two perpendicular diameters at entry equal or superior to 1cm.
5. Has laboratory function within specified parameters (may be repeated):

1. Adequate bone marrow function: absolute neutrophil count (ANC) ≥ 500/mL; hemoglobin ≥ 8.5 g/dL, platelets ≥ 50,000/mL
2. Adequate liver function: transaminases (aspartate aminotransferase/ alanine aminotransferase, AST/ALT) and alkaline phosphatase ≤ 3 (≤ 5 X the upper limit of normal (ULN) in the setting of liver metastasis or infiltration with malignant cells) x ULN; bilirubin ≤ 1.5 x ULN
3. Adequate renal function: creatinine clearance ≥ 60 mL/min (Cockcroft and Gault)
4. Adequate blood coagulation: international normalized ratio (INR) ≤ 2.3
5. Serum amylase and lipase ≤ 1.5 x ULN
6. Has adequate performance status (PS): Eastern Co-operative Oncology Group (ECOG) PS 0-2
7. Has received the final dose of any of the following treatments/ procedures with the specified minimum intervals before first dose of study drug (unless in the opinion of the investigator and the study medical coordinator the treatments/ procedures will not compromise patient safety or interfere with study conduct and with IDMC agreement):

* Chemotherapy, immunotherapy, or systemic radiation therapy - 14 days or ≥ 5 half-lives (whichever is shorter)
* Focal radiation therapy - 7 days
* Systemic and topical corticosteroids - 7 days
* Surgery with general anesthesia - 7 days
* Surgery with local anesthesia - 3 days
8. May continue endocrine therapies (e.g. for breast or prostate cancer) and/or anti-human epidermal growth factor (Her2) therapies while on this study
9. Women of childbearing potential must have a negative baseline blood or urine pregnancy test within 72 hours of first study therapy. Women may be neither breastfeeding nor intending to become pregnant during study participation and must agree to use effective contraceptive methods (hormonal or barrier method of birth control, or true abstinence) for the duration of study participation and in the following 90 days after discontinuation of study treatment
10. Male patients with partners of childbearing potential must take appropriate precautions to avoid fathering a child from screening until 90 days after discontinuation of study treatment and use appropriate barrier contraception or true abstinence
11. Must not be receiving any other investigational medicinal product


1. Is able to understand and voluntarily sign a written informed consent and is willing and able to comply with the protocol requirements including scheduled visits, treatment plan, laboratory tests and other study procedures
2. Is aged ≥ 18 years
3. Has pathologically confirmed metastatic pancreatic cancer AND is previously untreated with systemic agents in the recurrence/metastatic setting.
4. Must have at least 1 measurable lesion per RECIST v1.1, measured preferably by computed tomography (CT) scan or magnetic resonance image (MRI)
5. Has laboratory function within specified parameters (may be repeated):

e. Adequate bone marrow function: absolute neutrophil count (ANC) ≥ 500/mL; hemoglobin ≥ 8.5 g/dL, platelets ≥ 75,000/mL f. Adequate liver function: transaminases (aspartate aminotransferase/ alanine aminotransferase, AST/ALT) and alkaline phosphatase ≤ 3 (≤ 10 X the upper limit of normal (ULN) in the setting of liver metastasis or infiltration with malignant cells) x ULN; bilirubin ≤ 1.5 x ULN Adequate renal function: creatinine clearance ≥ 30 mL/min (Cockcroft and Gault)
6. Has Eastern Co-operative Oncology Group (ECOG) PS 0 or 1
7. Has received the final dose of any of the following treatments/ procedures with the specified minimum intervals before first dose of study drug:

* Focal radiation therapy - 7 days
* Surgery with general anesthesia - 7 days
* Surgery with local anesthesia - 3 days
8. May have received treatment with fluorouracil or gemcitabine as a radiation sensitizer in the adjuvant setting if the treatment was received at least 6 months before study enrollment
9. May have received neoadjuvant chemotherapy with FOLFIRINOX if last dose given at least 6 months before study enrollment
10. May have received prior cytotoxic doses of systemic chemotherapy in the adjuvant setting if last dose given at least 6 months before study enrollment
11. Women of childbearing potential must have a negative baseline blood or urine pregnancy test within 72 hours of first study therapy. Women may be neither breastfeeding nor intending to become pregnant during study participation and must agree to use effective contraceptive methods (hormonal or barrier method of birth control, or true abstinence) for the duration of study participation and in the following 90 days after discontinuation of study treatment
12. Male patients with partners of childbearing potential must take appropriate precautions to avoid fathering a child from screening until 90 days after discontinuation of study treatment and use appropriate barrier contraception or true abstinence
13. Must not be receiving any other investigational medicinal product

Patient who meets ANY of the following criteria is not eligible for this Part 3 study Arm B:

Exclusion Criteria

* Patient -

1. Is pregnant or lactating
2. Is known to be hypersensitive to any of the components of 9-ING-41 or to the excipients used in its formulation
3. Has not recovered from clinically significant toxicities as a result of prior anticancer therapy, except alopecia and infertility. Recovery is defined as ≤ Grade 2 CTCAE Version 4.03
4. Has significant cardiovascular impairment: history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, or stroke within 6 months of the first dose of 9-ING-41, or cardiac arrhythmia requiring medical treatment detected at screening
5. Has had a myocardial infarction within 12 weeks of the first dose of 9-ING-41 or has electrocardiogram (ECG) abnormalities that are deemed medically relevant by the investigator or study medical coordinator
6. Has known symptomatic rapidly progressive brain metastases or leptomeningeal involvement as assessed by CT scan or MRI. Patients with stable asymptomatic brain metastases or leptomeningeal disease or slowly progressive disease are eligible provided that they have not required new treatments for this disease in a 28-day period before the first dose of study drug, and anticonvulsants and steroids are at a stable dose for a period of 14 days prior to the first dose of study drug
7. Has had major surgery (not including placement of central lines) within 7 days prior to study entry or is planned to have major surgery during the course of the study (major surgery may be defined as any invasive operative procedure in which an extensive resection is performed, e.g. a body cavity is entered, organs are removed, or normal anatomy is altered. In general, if a mesenchymal barrier is opened (pleural cavity, peritoneum, meninges), the surgery is considered major)
8. Has any medical and/or social condition which, in the opinion of the investigator or study medical coordinator would preclude study participation
9. Has received an investigational anti-cancer drug in the 14-day period before the first dose of study drug (or within 5 half-lives if longer) or is currently participating in another interventional clinical trial
10. Has a current active malignancy other than the target cancer
11. Is considered to be a member of a vulnerable population (for example, prisoners)


1. Is pregnant or lactating
2. Is known to be hypersensitive to any of the components of 9-ING-41 or to the excipients used in its formulation
3. Has endocrine or acinar pancreatic carcinoma
4. Has not recovered from clinically significant toxicities as a result of prior anticancer therapy, except alopecia and/or infertility. Recovery is defined as ≤ Grade 2 severity per CTCAE, v5.0
5. Has significant cardiovascular impairment: history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, or stroke within 6 months of the first dose of study therapy, or uncontrolled cardiac arrhythmia
6. Has had a myocardial infarction within 12 weeks of the first dose of study therapy or has electrocardiogram (ECG) abnormalities that are deemed medically relevant by the investigator
7. Has symptomatic rapidly progressive brain metastases or leptomeningeal involvement as assessed by CT scan or MRI. Patients with stable brain metastases or leptomeningeal disease or slowly progressive disease are eligible provided that they have not required new treatments for this disease in a 28-day period before the first dose of study drug, and anticonvulsants and steroids are at a stable dose for a period of 14 days prior to the first dose of study drug
8. Has had major surgery (not including placement of central lines) within 7 days prior to study entry or is planned to have major surgery during the course of the study (major surgery may be defined as any invasive operative procedure in which an extensive resection is performed, e.g., a body cavity is entered, organs are removed, or normal anatomy is altered. In general, if a mesenchymal barrier is opened (pleural cavity, peritoneum, meninges), the surgery is considered major)
9. Has any medical and/or social condition which, in the opinion of the investigator or study medical coordinator would preclude study participation.
10. Has received an investigational anti-cancer drug in the 14-day period before the first dose of study drug (or within 5 half-lives if longer) or is currently participating in another interventional clinical trial.
11. Has a current active malignancy other than pancreatic cancer
12. Is considered to be a member of a vulnerable population (for example, prisoners).
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Actuate Therapeutics Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Mayo Clinic

Phoenix, Arizona, United States

Site Status

Arizona Oncology Associates

Tucson, Arizona, United States

Site Status

The University of Arizona Cancer Center

Tucson, Arizona, United States

Site Status

University of California Irvine Health

Orange, California, United States

Site Status

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, United States

Site Status

Christiana Care Health Services

Newark, Delaware, United States

Site Status

Sibley Memorial Hospital

Washington D.C., District of Columbia, United States

Site Status

Florida Cancer Specialists - South

Fort Myers, Florida, United States

Site Status

Miami Cancer Institute

Miami, Florida, United States

Site Status

Florida Cancer Specialists - North

St. Petersburg, Florida, United States

Site Status

Robert H. Lurie Comprehensive Cancer Center of Northwestern University

Chicago, Illinois, United States

Site Status

Des Moines Oncology Research Association

Des Moines, Iowa, United States

Site Status

Kansas University Cancer Center

Kansas City, Kansas, United States

Site Status

Ochsner Clinic Foundation

New Orleans, Louisiana, United States

Site Status

University of Michigan

Ann Arbor, Michigan, United States

Site Status

MetroMetro-Minnesota Community Oncology Research Consortium (MMCORC)

Minneapolis, Minnesota, United States

Site Status

Mayo Clinic

Rochester, Minnesota, United States

Site Status

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, United States

Site Status

Morristown Medical Center

Morristown, New Jersey, United States

Site Status

Capital Health Medical Center/ Hopewell

Pennington, New Jersey, United States

Site Status

MD Anderson Cancer Center at Cooper

Voorhees Township, New Jersey, United States

Site Status

Columbia University- Irving Medical Center

New York, New York, United States

Site Status

Stony Brook University Hospital

Stony Brook, New York, United States

Site Status

Duke University Medical Center

Durham, North Carolina, United States

Site Status

Oregon Health and Science University

Portland, Oregon, United States

Site Status

St. Luke's University Health Network

Bethlehem, Pennsylvania, United States

Site Status

Allegheny Health Network

Pittsburgh, Pennsylvania, United States

Site Status

Rhode Island Hospital

Providence, Rhode Island, United States

Site Status

Prisma Health Cancer Institute

Greenville, South Carolina, United States

Site Status

Sanford Research

Sioux Falls, South Dakota, United States

Site Status

West Cancer Center

Germantown, Tennessee, United States

Site Status

Baptist Clinical Research Institute

Memphis, Tennessee, United States

Site Status

Sarah Cannon Research Institute- Tennessee Oncology-Nashville

Nashville, Tennessee, United States

Site Status

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, United States

Site Status

Texas Oncology- Charles A. Sammons Cancer Center

Dallas, Texas, United States

Site Status

UT Southwestern Medical Center

Dallas, Texas, United States

Site Status

Utah Cancer Specialists

Salt Lake City, Utah, United States

Site Status

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States

Site Status

West Virginia University

Morgantown, West Virginia, United States

Site Status

UW Carbone Cancer Center

Madison, Wisconsin, United States

Site Status

UZA- Antwerpen

Edegem, Antwerp, Belgium

Site Status

Imelda VZW

Bonheiden, , Belgium

Site Status

UZ Gent

Ghent, , Belgium

Site Status

UZ Leuven Gasthuisberg

Leuven, , Belgium

Site Status

Cross Cancer Institute

Edmonton, Alberta, Canada

Site Status

QE II Health Sciences Centre

Halifax, Nova Scotia, Canada

Site Status

Centre Intégré de Santé et de Services Sociaux de la Montérégie-Centre

Greenfield Park, Quebec, Canada

Site Status

Jewish General Hospital

Montreal, Quebec, Canada

Site Status

McGill University Health Centre

Montreal, Quebec, Canada

Site Status

Centre Hospitalier Universitaire de Sherbrooke

Sherbrooke, Quebec, Canada

Site Status

Center Hospitalier Regional Universitaire de Besancon - Site Jean Minjoz

Besançon, Bourgogne-Franche-Comté, France

Site Status

CHRU Brest Hopital Morvan

Brest, Brittany Region, France

Site Status

Hopital Claude Huriez

Lille, Hauts-de-France, France

Site Status

Institute de Cancerologie de Lorraine

Vandœuvre-lès-Nancy, Meurthe-et-Moselle, France

Site Status

Institut Bergonie

Bordeaux, Nouvelle-Aquitaine, France

Site Status

Insitut de Cancerologie de l'Ouest

Saint-Herblain, Pays de la Loire Region, France

Site Status

Hopital de la Timone

Marseille, , France

Site Status

Netherlands Cancer Institute

Amsterdam, , Netherlands

Site Status

Fundacao Champalimaud

Lisbon, , Portugal

Site Status

Hospital Da Luz

Lisbon, , Portugal

Site Status

Centro Hospitalar Universitario Sao Joao

Porto, , Portugal

Site Status

Vall d'Hebron Institute of Oncology

Barcelona, , Spain

Site Status

Institut Catala d'Oncologia

Barcelona, , Spain

Site Status

Hospital Clinico U San Carlos (HSC)

Madrid, , Spain

Site Status

START Madrid-HM CIOCC Hospital Universitario

Madrid, , Spain

Site Status

INCLIVA University of Valencia

Valencia, , Spain

Site Status

Countries

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United States Belgium Canada France Netherlands Portugal Spain

References

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Ugolkov AV, Bondarenko GI, Dubrovskyi O, Berbegall AP, Navarro S, Noguera R, O'Halloran TV, Hendrix MJ, Giles FJ, Mazar AP. 9-ING-41, a small-molecule glycogen synthase kinase-3 inhibitor, is active in neuroblastoma. Anticancer Drugs. 2018 Sep;29(8):717-724. doi: 10.1097/CAD.0000000000000652.

Reference Type BACKGROUND
PMID: 29846250 (View on PubMed)

Karmali R, Chukkapalli V, Gordon LI, Borgia JA, Ugolkov A, Mazar AP, Giles FJ. GSK-3beta inhibitor, 9-ING-41, reduces cell viability and halts proliferation of B-cell lymphoma cell lines as a single agent and in combination with novel agents. Oncotarget. 2017 Nov 11;8(70):114924-114934. doi: 10.18632/oncotarget.22414. eCollection 2017 Dec 29.

Reference Type BACKGROUND
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Ugolkov A, Qiang W, Bondarenko G, Procissi D, Gaisina I, James CD, Chandler J, Kozikowski A, Gunosewoyo H, O'Halloran T, Raizer J, Mazar AP. Combination Treatment with the GSK-3 Inhibitor 9-ING-41 and CCNU Cures Orthotopic Chemoresistant Glioblastoma in Patient-Derived Xenograft Models. Transl Oncol. 2017 Aug;10(4):669-678. doi: 10.1016/j.tranon.2017.06.003. Epub 2017 Jun 30.

Reference Type BACKGROUND
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Ugolkov A, Gaisina I, Zhang JS, Billadeau DD, White K, Kozikowski A, Jain S, Cristofanilli M, Giles F, O'Halloran T, Cryns VL, Mazar AP. GSK-3 inhibition overcomes chemoresistance in human breast cancer. Cancer Lett. 2016 Oct 1;380(2):384-392. doi: 10.1016/j.canlet.2016.07.006. Epub 2016 Jul 14.

Reference Type BACKGROUND
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Pal K, Cao Y, Gaisina IN, Bhattacharya S, Dutta SK, Wang E, Gunosewoyo H, Kozikowski AP, Billadeau DD, Mukhopadhyay D. Inhibition of GSK-3 induces differentiation and impaired glucose metabolism in renal cancer. Mol Cancer Ther. 2014 Feb;13(2):285-96. doi: 10.1158/1535-7163.MCT-13-0681. Epub 2013 Dec 10.

Reference Type BACKGROUND
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Walz A, Ugolkov A, Chandra S, Kozikowski A, Carneiro BA, O'Halloran TV, Giles FJ, Billadeau DD, Mazar AP. Molecular Pathways: Revisiting Glycogen Synthase Kinase-3beta as a Target for the Treatment of Cancer. Clin Cancer Res. 2017 Apr 15;23(8):1891-1897. doi: 10.1158/1078-0432.CCR-15-2240. Epub 2017 Jan 4.

Reference Type BACKGROUND
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Ugolkov AV, Matsangou M, Taxter TJ, O'Halloran TV, Cryns VL, Giles FJ, Mazar AP. Aberrant expression of glycogen synthase kinase-3beta in human breast and head and neck cancer. Oncol Lett. 2018 Nov;16(5):6437-6444. doi: 10.3892/ol.2018.9483. Epub 2018 Sep 21.

Reference Type BACKGROUND
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Sahin I, Eturi A, De Souza A, Pamarthy S, Tavora F, Giles FJ, Carneiro BA. Glycogen synthase kinase-3 beta inhibitors as novel cancer treatments and modulators of antitumor immune responses. Cancer Biol Ther. 2019;20(8):1047-1056. doi: 10.1080/15384047.2019.1595283. Epub 2019 Apr 12.

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Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

1801

Identifier Type: -

Identifier Source: org_study_id

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