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AzTrials

CancerPhase 2NCT03678883

9-ING-41 in Patients With Advanced Cancers

A Phase 2 study testing 9-ING-41, Gemcitabine - 21 day cycle and Doxorubicin. in people with Cancer and Pancreatic Cancer, run by Actuate Therapeutics Inc. at 66 sites in 7 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Cancer, Pancreatic Cancer, Sarcoma
What is being tested?
9-ING-41, Gemcitabine - 21 day cycle and Doxorubicin.
Could I receive a placebo?
No, everyone receives an active treatment
How many people
350 participants
Where
66 sitesin 7 countries
Study dates
4 Jan 2019to Jun 2026
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patient -
  • 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.
  • Is aged ≥ 18 years
  • Has pathologically confirmed advanced or metastatic malignancy characterized by one or more of the following:
  • Patient is intolerant of existing therapy(ies) known to provide clinical benefit for their condition
  • Malignancy is refractory to existing therapy(ies) known to potentially provide clinical benefit
Show all 26Show fewer
  • Malignancy has relapsed after standard therapy
  • Malignancy for which there is no standard therapy that improves survival by at least 3 months
  • 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.
  • Has laboratory function within specified parameters (may be repeated):
  • Adequate bone marrow function: absolute neutrophil count (ANC) ≥ 500/mL; hemoglobin ≥ 8.5 g/dL, platelets ≥ 50,000/mL
  • 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
  • Adequate renal function: creatinine clearance ≥ 60 mL/min (Cockcroft and Gault)
  • Adequate blood coagulation: international normalized ratio (INR) ≤ 2.3
  • Serum amylase and lipase ≤ 1.5 x ULN
  • Has adequate performance status (PS): Eastern Co-operative Oncology Group (ECOG) PS 0-2
  • 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
  • May continue endocrine therapies (e.g. for breast or prostate cancer) and/or anti-human epidermal growth factor (Her2) therapies while on this study
  • 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
  • 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
  • Must not be receiving any other investigational medicinal product

Who cannot join

  • Patient -
  • Is pregnant or lactating
  • Is known to be hypersensitive to any of the components of 9-ING-41 or to the excipients used in its formulation
  • 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
  • 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
  • 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
Show all 43Show fewer
  • 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
  • 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)
  • Has any medical and/or social condition which, in the opinion of the investigator or study medical coordinator would preclude study participation
  • 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
  • Has a current active malignancy other than the target cancer
  • Is considered to be a member of a vulnerable population (for example, prisoners)
  • Part 3 ARMB Inclusion Criteria: Patient -
  • 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
  • Is aged ≥ 18 years
  • Has pathologically confirmed metastatic pancreatic cancer AND is previously untreated with systemic agents in the recurrence/metastatic setting.
  • Must have at least 1 measurable lesion per RECIST v1.1, measured preferably by computed tomography (CT) scan or magnetic resonance image (MRI)
  • Has laboratory function within specified parameters (may be repeated):
  • 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)
  • Has Eastern Co-operative Oncology Group (ECOG) PS 0 or 1
  • 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
  • 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
  • May have received neoadjuvant chemotherapy with FOLFIRINOX if last dose given at least 6 months before study enrollment
  • May have received prior cytotoxic doses of systemic chemotherapy in the adjuvant setting if last dose given at least 6 months before study enrollment
  • 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
  • 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
  • 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:
  • Is pregnant or lactating
  • Is known to be hypersensitive to any of the components of 9-ING-41 or to the excipients used in its formulation
  • Has endocrine or acinar pancreatic carcinoma
  • 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
  • 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
  • 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
  • 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
  • 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)
  • Has any medical and/or social condition which, in the opinion of the investigator or study medical coordinator would preclude study participation.
  • 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.
  • Has a current active malignancy other than pancreatic cancer
  • Is considered to be a member of a vulnerable population (for example, prisoners).

Trial locations and contacts

66 sites in 7 countries.

66 sites in 7 countries

United States40 sites

  • University of Michigan

    Ann Arbor, Michigan, 48109

  • St. Luke's University Health Network

    Bethlehem, Pennsylvania, 18015

  • Robert H. Lurie Comprehensive Cancer Center of Northwestern University

    Chicago, Illinois, 60611

  • Texas Oncology- Charles A. Sammons Cancer Center

    Dallas, Texas, 75246

  • UT Southwestern Medical Center

    Dallas, Texas, 75390

  • Des Moines Oncology Research Association

    Des Moines, Iowa, 50309

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • Florida Cancer Specialists - South

    Fort Myers, Florida, 33901

  • West Cancer Center

    Germantown, Tennessee, 38138

  • Prisma Health Cancer Institute

    Greenville, South Carolina, 26905

  • Kansas University Cancer Center

    Kansas City, Kansas, 66160

  • Comprehensive Cancer Centers of Nevada

    Las Vegas, Nevada, 89128

  • UW Carbone Cancer Center

    Madison, Wisconsin, 53792

  • Baptist Clinical Research Institute

    Memphis, Tennessee, 38120

  • Miami Cancer Institute

    Miami, Florida, 33176

  • MetroMetro-Minnesota Community Oncology Research Consortium (MMCORC)

    Minneapolis, Minnesota, 55416

  • West Virginia University

    Morgantown, West Virginia, 26506

  • Morristown Medical Center

    Morristown, New Jersey, 07960

  • Sarah Cannon Research Institute- Tennessee Oncology-Nashville

    Nashville, Tennessee, 37203

  • Vanderbilt-Ingram Cancer Center

    Nashville, Tennessee, 37232

  • Ochsner Clinic Foundation

    New Orleans, Louisiana, 70121

  • Columbia University- Irving Medical Center

    New York, New York, 10032

  • Christiana Care Health Services

    Newark, Delaware, 19709

  • University of California Irvine Health

    Orange, California, 92868

  • Capital Health Medical Center/ Hopewell

    Pennington, New Jersey, 08534

  • Mayo Clinic

    Phoenix, Arizona, 85054

  • Allegheny Health Network

    Pittsburgh, Pennsylvania, 15212

  • Oregon Health and Science University

    Portland, Oregon, 97239

  • Rhode Island Hospital

    Providence, Rhode Island, 02903

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • Utah Cancer Specialists

    Salt Lake City, Utah, 84124

  • UCSF Helen Diller Family Comprehensive Cancer Center

    San Francisco, California, 94115

  • Fred Hutchinson Cancer Research Center

    Seattle, Washington, 98109

  • Sanford Research

    Sioux Falls, South Dakota, 57105

  • Florida Cancer Specialists - North

    St. Petersburg, Florida, 33705

  • Stony Brook University Hospital

    Stony Brook, New York, 11794

  • Arizona Oncology Associates

    Tucson, Arizona, 85704

  • The University of Arizona Cancer Center

    Tucson, Arizona, 85719

  • MD Anderson Cancer Center at Cooper

    Voorhees Township, New Jersey, 08043

  • Sibley Memorial Hospital

    Washington D.C., District of Columbia, 20016

Other trials in United States

France7 sites

  • Center Hospitalier Regional Universitaire de Besancon - Site Jean Minjoz

    Besançon, Bourgogne-Franche-Comté, 25030

  • Institut Bergonie

    Bordeaux, New Aquitaine, 33076

  • CHRU Brest Hopital Morvan

    Brest, Brittany Region, 29200

  • Hopital Claude Huriez

    Lille, Hauts-de-France, 59037

  • Hopital de la Timone

    Marseille, 13005

  • Insitut de Cancerologie de l'Ouest

    Saint-Herblain, Pays de la Loire Region, 44800

  • Institute de Cancerologie de Lorraine

    Vandœuvre-lès-Nancy, Meurthe-et-Moselle, 54500

Other trials in France

Canada6 sites

  • Cross Cancer Institute

    Edmonton, Alberta, T6G 1Z2

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

    Greenfield Park, Quebec, G4V 2H1

  • QE II Health Sciences Centre

    Halifax, Nova Scotia, B3H 2Y9

  • Jewish General Hospital

    Montreal, Quebec, H3T 1E2

  • McGill University Health Centre

    Montreal, Quebec, H4A 3J1

  • Centre Hospitalier Universitaire de Sherbrooke

    Sherbrooke, Quebec, J1H 5N4

Other trials in Canada

Spain5 sites

  • Vall d'Hebron Institute of Oncology

    Barcelona, 08035

  • Institut Catala d'Oncologia

    Barcelona, 8908

  • Hospital Clinico U San Carlos (HSC)

    Madrid, 28050

  • START Madrid-HM CIOCC Hospital Universitario

    Madrid, 28050

  • INCLIVA University of Valencia

    Valencia, 46010

Other trials in Spain

Belgium4 sites

  • Imelda VZW

    Bonheiden, 2820

  • UZA- Antwerpen

    Edegem, Antwerp, 2650

  • UZ Gent

    Ghent, 9000

  • UZ Leuven Gasthuisberg

    Leuven, 3000

Other trials in Belgium

Portugal3 sites

  • Fundacao Champalimaud

    Lisbon, 1400-038

  • Hospital Da Luz

    Lisbon, 1500-650

  • Centro Hospitalar Universitario Sao Joao

    Porto, 4200-319

Other trials in Portugal

Netherlands1 site

  • Netherlands Cancer Institute

    Amsterdam, 1066 CX

Other trials in Netherlands

About this study

Official title: Phase 1/2 Study of 9-ING-41, a Glycogen Synthase Kinase-3 Beta (GSK-3β) Inhibitor, as a Single Agent and Combined With Chemotherapy, in Patients With Refractory Hematologic Malignancies or Solid Tumors

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.

Read the detailed description

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.
Being tested
9-ING-41, Gemcitabine - 21 day cycle, Doxorubicin., Lomustine, Carboplatin.
Keywords
Refractory cancers, 9-ING-41, Glycogen Synthase Kinase, GSK-3β, NF-κβ, Apoptosis, Chemoresistance, DNA damage response DDR, Ataxia telangiectasia mutated and Rad3 related ATR, Checkpoint kinase 1 CHK1, Checkpoint Inhibitor, LAG-3, ATLL
Medical subject headings
Neoplasms, Pancreatic Neoplasms, Sarcoma, Kidney Neoplasms, Lymphoma, Non-Hodgkin, Neoplasm Metastasis, Bone Neoplasms, Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 9-ING-41Drug

    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 cycleDrug

    Also called Gemzar

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

  • Doxorubicin.Drug

    Also called Doxil, Adriamycin

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

  • LomustineDrug

    Also called CCNU, Gleostine

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

  • Carboplatin.Drug

    Also called Paraplatin

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

  • Nab paclitaxel.Drug

    Also called Abraxane, Protein-bound paclitaxel, Nanoparticle albumin-bound paclitaxel

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

  • Paclitaxel.Drug

    Also called Taxol

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

  • Gemcitabine - 28 day cycleDrug

    Also called Gemzar

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

  • IrinotecanDrug

    Also called Camptosar

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

Study groups in NCT03678883
Study groupRoleWhat they receive
9-ING-41ExperimentalDrug: 9-ING-41
Receives: Drug: 9-ING-41
9-ING-41 plus GemcitabineExperimentalDrugs: Gemcitabine - 21 day cycle. 9-ING-41
Receives: Drug: 9-ING-41; Drug: Gemcitabine - 21 day cycle
9-ING-41 plus DoxorubicinExperimentalDrugs: Doxorubicin. 9-ING-41
Receives: Drug: 9-ING-41; Drug: Doxorubicin.
9-ING-41 plus LomustineExperimentalDrugs: Lomustine. 9-ING-41.
Receives: Drug: 9-ING-41; Drug: Lomustine
9-ING-41 plus CarboplatinExperimentalDrugs: Carboplatin. 9-ING-41.
Receives: Drug: 9-ING-41; Drug: Carboplatin.
9-ING-41 plus nab paclitaxel GemcitabineExperimentalDrugs: Nab-paclitaxel. Gemcitabine - 28 day cycle. 9-ING-41.
Receives: Drug: 9-ING-41; Drug: Nab paclitaxel.; Drug: Gemcitabine - 28 day cycle
9-ING-41 plus Paclitaxel/CarboplatinExperimentalDrugs: Paclitaxel. Carboplatin. 9-ING-41.
Receives: Drug: 9-ING-41; Drug: Carboplatin.; Drug: Paclitaxel.
9-ING-41 plus IrinotecanExperimentalDrugs: Irinotecan. 9-ING-41.
Receives: Drug: 9-ING-41; Drug: Irinotecan

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Parts 1/2: Number of participants with treatment-related adverse events as assessed by CTCAE v4.03

    The standard assessments used to assign a score to any affected organ system as per the NCI CTCAE 4.03 will be conduced at each protocol-specified timepoint.

    Measured: 3 months to 3 years

  2. Part 3 Arm B

    To determine the 1-year survival rate of patients treated on the 9-ING-41 schedule chosen from the run-in stage of the study compared to the control arm

    Measured: 3 months to 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Sep 2018
  2. Study start4 Jan 2019
  3. Primary completionJun 2026 (estimated)
  4. Study completionJun 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
350 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03678883
Sponsor's protocol ID
1801
Status last verified
Mar 2026
First submitted
15 Sep 2018
Last updated
3 Apr 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 29846250

  • 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.

    PubMed 29383130

  • 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.

    PubMed 28672195

  • 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.

    PubMed 27424289

  • 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.

    PubMed 24327518

  • 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.

    PubMed 28053024

  • 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.

    PubMed 30405781

  • 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.

    PubMed 30975030

  • Wu X, Stenson M, Abeykoon J, Nowakowski K, Zhang L, Lawson J, Wellik L, Li Y, Krull J, Wenzl K, Novak AJ, Ansell SM, Bishop GA, Billadeau DD, Peng KW, Giles F, Schmitt DM, Witzig TE. Targeting glycogen synthase kinase 3 for therapeutic benefit in lymphoma. Blood. 2019 Jul 25;134(4):363-373. doi: 10.1182/blood.2018874560. Epub 2019 May 17.

    PubMed 31101621

  • Ding L, Madamsetty VS, Kiers S, Alekhina O, Ugolkov A, Dube J, Zhang Y, Zhang JS, Wang E, Dutta SK, Schmitt DM, Giles FJ, Kozikowski AP, Mazar AP, Mukhopadhyay D, Billadeau DD. Glycogen Synthase Kinase-3 Inhibition Sensitizes Pancreatic Cancer Cells to Chemotherapy by Abrogating the TopBP1/ATR-Mediated DNA Damage Response. Clin Cancer Res. 2019 Nov 1;25(21):6452-6462. doi: 10.1158/1078-0432.CCR-19-0799. Epub 2019 Sep 18.

    PubMed 31533931

  • Jeffers A, Qin W, Owens S, Koenig KB, Komatsu S, Giles FJ, Schmitt DM, Idell S, Tucker TA. Glycogen Synthase Kinase-3beta Inhibition with 9-ING-41 Attenuates the Progression of Pulmonary Fibrosis. Sci Rep. 2019 Dec 12;9(1):18925. doi: 10.1038/s41598-019-55176-w.

    PubMed 31831767

  • Kuroki H, Anraku T, Kazama A, Bilim V, Tasaki M, Schmitt D, Mazar AP, Giles FJ, Ugolkov A, Tomita Y. 9-ING-41, a small molecule inhibitor of GSK-3beta, potentiates the effects of anticancer therapeutics in bladder cancer. Sci Rep. 2019 Dec 27;9(1):19977. doi: 10.1038/s41598-019-56461-4.

    PubMed 31882719

  • Anraku T, Kuroki H, Kazama A, Bilim V, Tasaki M, Schmitt D, Mazar A, Giles FJ, Ugolkov A, Tomita Y. Clinically relevant GSK-3beta inhibitor 9-ING-41 is active as a single agent and in combination with other antitumor therapies in human renal cancer. Int J Mol Med. 2020 Feb;45(2):315-323. doi: 10.3892/ijmm.2019.4427. Epub 2019 Dec 12.

    PubMed 31894292

  • Mahalingam D, Shroff RT, Carneiro BA, Ji Y, Coveler AL, Cervantes A, Sahai V, Ploquin A, Hiret S, LoConte NK, Percent IJ, Lopez CD, Pernot S, Kavan P, Mulcahy M, Carr R, Giles FJ, Seifarth C, Ugolkov A, Weiskittel T, Fine G, Jaros M, Mazar AP, Bekaii-Saab TS. Elraglusib and chemotherapy in metastatic pancreatic ductal adenocarcinoma: a randomized controlled phase 2 trial. Nat Med. 2026 May;32(5):1794-1804. doi: 10.1038/s41591-026-04327-4. Epub 2026 Apr 14.

    PubMed 41981308

  • Hsu A, Huntington KE, De Souza A, Zhou L, Olszewski AJ, Makwana NP, Treaba DO, Cavalcante L, Giles FJ, Safran H, El-Deiry WS, Carneiro BA. Clinical activity of 9-ING-41, a small molecule selective glycogen synthase kinase-3 beta (GSK-3beta) inhibitor, in refractory adult T-Cell leukemia/lymphoma. Cancer Biol Ther. 2022 Dec 31;23(1):417-423. doi: 10.1080/15384047.2022.2088984.

    PubMed 35815408

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing 9-ING-41, Gemcitabine - 21 day cycle and Doxorubicin. in people with Cancer and Pancreatic Cancer, run by Actuate Therapeutics Inc. at 66 sites in 7 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 26 inclusion and 43 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 3 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 66 sites in United States, France, Canada, Spain, Belgium and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Parts 1/2: Number of participants with treatment-related adverse events as assessed by CTCAE v4.03 (time frame: 3 months to 3 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03678883, which also lists 16 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Apr 2026.

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