Accepts Healthy Volunteers
Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms
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.
|Eligible Ages||18 Years and Over|
- - 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 8.
- - Patient - 1.
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.
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 1/Phase 2|
The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.
|Actuate Therapeutics Inc.|
The person who is responsible for the scientific and technical direction of the entire clinical study.
|Francis J Giles, MD|
|Principal Investigator Affiliation||Actuate Therapeutics|
Category of organization(s) involved as sponsor (and collaborator) supporting the trial.
|Countries||Netherlands, United States|
The disease, disorder, syndrome, illness, or injury that is being studied.
|Cancer, Lymphoma, Pancreatic Cancer, Glioblastoma Multiforme, Sarcoma, Breast Cancer, Bladder Cancer, Renal Cancer, Ovarian Cancer, Refractory Cancer, Refractory Neoplasm, Refractory Non-Hodgkin Lymphoma, Refractory Brain Tumor, 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|
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 study will have three parts:
- - 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 - Part 2: 9-ING-41 combined with standard anticancer agents: The 3+3 dose escalation study design will be used for 7 chemotherapy combination regimens (9-ING-41 plus gemcitabine, doxorubicin, lomustine, carboplatin, irinotecan, nab-paclitaxel plus gemcitabine, paclitaxel plus carboplatin) to identify the MTD/RP2D of each regimen.
- - Part 3: Assessment of activity of 9-ING-41 based combination regimens: The primary objective for Study Part 3 is to assess the clinical benefit of each of the seven 9-ING-41-based combination regimens.
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.
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.