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9-ING-41 in Patients with Advanced Cancers
Study Purpose
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.
Recruitment Criteria
Accepts Healthy Volunteers
Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms |
No |
Study Type
An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies. |
Interventional |
Eligible Ages | 18 Years and Over |
Gender | All |
Inclusion Criteria:
- - Patient - 1.
- - 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).
- - 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.
Exclusion Criteria:
- - Patient - 1.
Inclusion Criteria:
Patient- - 1.
- - Focal radiation therapy - 7 days.
- - Surgery with general anesthesia - 7 days.
- - Surgery with local anesthesia - 3 days.
Exclusion Criteria:
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).Trial Details
Trial ID:
This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries. |
NCT03678883 |
Phase
Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use. |
Phase 2 |
Lead Sponsor
The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data. |
Actuate Therapeutics Inc. |
Principal Investigator
The person who is responsible for the scientific and technical direction of the entire clinical study. |
N/A |
Principal Investigator Affiliation | N/A |
Agency Class
Category of organization(s) involved as sponsor (and collaborator) supporting the trial. |
Industry |
Overall Status | Active, not recruiting |
Countries | Belgium, Canada, France, Netherlands, Portugal, Spain, United States |
Conditions
The disease, disorder, syndrome, illness, or injury that is being studied. |
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 |
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.
Arms
Experimental: 9-ING-41
Drug: 9-ING-41
Experimental: 9-ING-41 plus Gemcitabine
Drugs: Gemcitabine - 21 day cycle. 9-ING-41
Experimental: 9-ING-41 plus Doxorubicin
Drugs: Doxorubicin. 9-ING-41
Experimental: 9-ING-41 plus Lomustine
Drugs: Lomustine. 9-ING-41.
Experimental: 9-ING-41 plus Carboplatin
Drugs: Carboplatin. 9-ING-41.
Experimental: 9-ING-41 plus nab paclitaxel Gemcitabine
Drugs: Nab-paclitaxel. Gemcitabine - 28 day cycle. 9-ING-41.
Experimental: 9-ING-41 plus Paclitaxel/Carboplatin
Drugs: Paclitaxel. Carboplatin. 9-ING-41.
Experimental: 9-ING-41 plus Irinotecan
Drugs: Irinotecan. 9-ING-41.
Interventions
Drug: - 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.
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
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.
Drug: - Lomustine
Lomustine 30 mg/m² orally as a single dose, weekly for twelve weeks.
Drug: - Carboplatin.
Carboplatin AUC 6 IV over 1 hour on Day 1 of a 21-day cycle.
Drug: - Nab paclitaxel.
Nab-paclitaxel 125 mg/m2 intravenously on Days 1, 8 and 15 of a 28-day cycle
Drug: - Paclitaxel.
Paclitaxel 175 mg/m2 intravenously over 3 hours on Day 1 of a 21-day cycle.
Drug: - Gemcitabine - 28 day cycle
Gemcitabine 1000 mg/m2 intravenously over 30-minutes on Days 1, 8 and 15 of a 28-day cycle
Drug: - Irinotecan
Irinotecan 350 mg/m2 intravenously over 90-minutes on Day 1 of a 21-day cycle
Contact a Trial Team
If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.
Status
Address
Mayo Clinic
Phoenix 5308655, Arizona 5551752, 85054
Status
Address
Arizona Oncology Associates
Tucson 5318313, Arizona 5551752, 85704
Status
Address
The University of Arizona Cancer Center
Tucson 5318313, Arizona 5551752, 85719
Status
Address
University of California Irvine Health
Orange 5379513, California 5332921, 92868
Status
Address
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco 5391959, California 5332921, 94115
Status
Address
Christiana Care Health Services
Newark 4143861, Delaware 4142224, 19709
Status
Address
Sibley Memorial Hospital
Washington D.C. 4140963, District of Columbia 4138106, 20016
Status
Address
Florida Cancer Specialists - South
Fort Myers 4155995, Florida 4155751, 33901
Status
Address
Miami Cancer Institute
Miami 4164138, Florida 4155751, 33176
Status
Address
Florida Cancer Specialists - North
St. Petersburg 4171563, Florida 4155751, 33705
Status
Address
Robert H. Lurie Comprehensive Cancer Center of Northwestern University
Chicago 4887398, Illinois 4896861, 60611
Status
Address
Des Moines Oncology Research Association
Des Moines 4853828, Iowa 4862182, 50309
Status
Address
Kansas University Cancer Center
Kansas City 4273837, Kansas 4273857, 66160
Status
Address
Ochsner Clinic Foundation
New Orleans 4335045, Louisiana 4331987, 70121
Status
Address
University of Michigan
Ann Arbor 4984247, Michigan 5001836, 48109
Status
Address
MetroMetro-Minnesota Community Oncology Research Consortium (MMCORC)
Minneapolis 5037649, Minnesota 5037779, 55416
Status
Address
Mayo Clinic
Rochester 5043473, Minnesota 5037779, 55905
Status
Address
Comprehensive Cancer Centers of Nevada
Las Vegas 5506956, Nevada 5509151, 89128
Status
Address
Morristown Medical Center
Morristown 5101427, New Jersey 5101760, 07960
Status
Address
Capital Health Medical Center/ Hopewell
Pennington 5102535, New Jersey 5101760, 08534
Status
Address
MD Anderson Cancer Center at Cooper
Voorhees Township 5105860, New Jersey 5101760, 08043
Status
Address
Columbia University- Irving Medical Center
New York 5128581, New York 5128638, 10032
Status
Address
Stony Brook University Hospital
Stony Brook 5139865, New York 5128638, 11794
Status
Address
Duke University Medical Center
Durham 4464368, North Carolina 4482348, 27710
Status
Address
Oregon Health and Science University
Portland 5746545, Oregon 5744337, 97239
Status
Address
St. Luke's University Health Network
Bethlehem 5180225, Pennsylvania 6254927, 18015
Status
Address
Allegheny Health Network
Pittsburgh 5206379, Pennsylvania 6254927, 15212
Status
Address
Rhode Island Hospital
Providence 5224151, Rhode Island 5224323, 02903
Status
Address
Prisma Health Cancer Institute
Greenville 4580543, South Carolina 4597040, 26905
Status
Address
Sanford Research
Sioux Falls 5231851, South Dakota 5769223, 57105
Status
Address
West Cancer Center
Germantown 4624601, Tennessee 4662168, 38138
Status
Address
Baptist Clinical Research Institute
Memphis 4641239, Tennessee 4662168, 38120
Status
Address
Sarah Cannon Research Institute- Tennessee Oncology-Nashville
Nashville 4644585, Tennessee 4662168, 37203
Status
Address
Vanderbilt-Ingram Cancer Center
Nashville 4644585, Tennessee 4662168, 37232
Status
Address
Texas Oncology- Charles A. Sammons Cancer Center
Dallas 4684888, Texas 4736286, 75246
Status
Address
UT Southwestern Medical Center
Dallas 4684888, Texas 4736286, 75390
Status
Address
Utah Cancer Specialists
Salt Lake City 5780993, Utah 5549030, 84124
Status
Address
Fred Hutchinson Cancer Research Center
Seattle 5809844, Washington 5815135, 98109
Status
Address
West Virginia University
Morgantown 4815352, West Virginia 4826850, 26506
Status
Address
UW Carbone Cancer Center
Madison 5261457, Wisconsin 5279468, 53792
International Sites
Status
Address
UZA- Antwerpen
Edegem 2799007, Antwerp, 2650
Status
Address
Imelda VZW
Bonheiden 2801539, , 2820
Status
Address
UZ Gent
Ghent 2797656, , 9000
Status
Address
UZ Leuven Gasthuisberg
Leuven 2792482, , 3000
Status
Address
Cross Cancer Institute
Edmonton 5946768, Alberta 5883102, T6G 1Z2
Status
Address
QE II Health Sciences Centre
Halifax 6324729, Nova Scotia 6091530, B3H 2Y9
Status
Address
Centre Intégré de Santé et de Services Sociaux de la Montérégie-Centre
Greenfield Park 5966078, Quebec 6115047, G4V 2H1
Status
Address
Jewish General Hospital
Montreal 6077243, Quebec 6115047, H3T 1E2
Status
Address
McGill University Health Centre
Montreal 6077243, Quebec 6115047, H4A 3J1
Status
Address
Centre Hospitalier Universitaire de Sherbrooke
Sherbrooke 6146143, Quebec 6115047, J1H 5N4
Status
Address
Center Hospitalier Regional Universitaire de Besancon - Site Jean Minjoz
Besançon 3033123, Bourgogne-Franche-Comté 11071619, 25030
Status
Address
CHRU Brest Hopital Morvan
Brest 3030300, Brittany Region 3030293, 29200
Status
Address
Hopital Claude Huriez
Lille 2998324, Hauts-de-France 11071624, 59037
Status
Address
Institute de Cancerologie de Lorraine
Vandœuvre-lès-Nancy 2970797, Meurthe-et-Moselle, 54500
Status
Address
Institut Bergonie
Bordeaux 3031582, Nouvelle-Aquitaine 11071620, 33076
Status
Address
Insitut de Cancerologie de l'Ouest
Saint-Herblain 2979590, Pays de la Loire Region 2988289, 44800
Status
Address
Hopital de la Timone
Marseille 2995469, , 13005
Status
Address
Netherlands Cancer Institute
Amsterdam 2759794, , 1066 CX
Status
Address
Fundacao Champalimaud
Lisbon 2267057, , 1400-038
Status
Address
Hospital Da Luz
Lisbon 2267057, , 1500-650
Status
Address
Centro Hospitalar Universitario Sao Joao
Porto 2735943, , 4200-319
Status
Address
Vall d'Hebron Institute of Oncology
Barcelona 3128760, , 08035
Status
Address
Institut Catala d'Oncologia
Barcelona 3128760, , 8908
Status
Address
Hospital Clinico U San Carlos (HSC)
Madrid 3117735, , 28050
Status
Address
START Madrid-HM CIOCC Hospital Universitario
Madrid 3117735, , 28050
Status
Address
INCLIVA University of Valencia
Valencia 2509954, , 46010