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Refractory CancerPhase 1NCT04239092

9-ING-41 in Pediatric Patients With Refractory Malignancies.

A Phase 1 study testing 9-ING-41, Irinotecan and Temozolomide in people with Refractory Cancer and Refractory Neoplasm, run by Actuate Therapeutics Inc. at 9 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial summary

9-ING-41 has anti-cancer clinical activity with no significant toxicity in adult patients. This Phase 1 study will study its efficacy in paediatric patients with advanced malignancies. Read more about this study

Who is it for?
Ages Up to 22 years
What is being tested?
9-ING-41, Irinotecan and Temozolomide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
9 sitesUnited States
Study dates
5 Jun 2020to 7 Jul 2025
Phase
Phase 1
Are there results?
None posted in the registry

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 Up to 22 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Patients must meet ALL the following criteria to be eligible for this study:
  • Age < 22 years of age
  • Diagnosis of recurrent or refractory malignancy with histologic verification of malignancy at original diagnosis or relapse, except patients with extra-cranial germ-cell tumors who have elevations of serum tumor markers including alpha-fetoprotein or beta-HCG, and/or patients with intrinsic brain stem tumors or patients with CNS-germ cell tumors and elevations of CSF or serum tumor markers including alpha-fetoprotein or beta-HCG.
  • Have either measurable or evaluable disease. Evaluable disease is defined as an assessment of tumor that cannot be measured using a ruler or calipers, but can be used to determine disease progression or response (e.g., positive lesions on MIBG or bone scan, metastatic bone marrow disease, elevated tumor markers, or presence of a malignant pleural effusion)
  • Have current disease state for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life
  • Have Performance Level: Karnofsky ≥ 50% for patients >16 years of age and Lansky ≥50 for patients ≤16 years of age
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  • Neurologic deficits in patients with CNS tumors must have been relatively stable for at least 7 days prior to study enrollment. Patients with CNS tumors who are receiving steroids must be on a stable or decreasing dose for at least 7 days prior to study entry. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
  • Have fully recovered from the acute clinically significant toxic effects of prior anti-cancer therapy
  • Myelosuppressive chemotherapy: On first day of treatment be at least 7 days after the last dose of myelosuppressive chemotherapy for single agent 9 ING 41, at least 21 days after the last dose of myelosuppressive chemotherapy for 9-ING-41 plus irinotecan
  • Hematopoietic growth factors: At least 14 days after the last dose of a long-acting growth factor or 7 days for short-acting growth factor
  • Biologic (anti-neoplastic agent): At least 7 days after the last dose of a biologic agent.
  • Monoclonal antibodies: At least 28 days after the last dose of a monoclonal antibody
  • At least 14 days after local palliative XRT (small port); At least 100 days must have elapsed if prior TBI, craniospinal XRT or if ≥ 50% radiation of pelvis; At least 42 days must have elapsed if other substantial BM radiation
  • Stem Cell Infusion without TBI: No evidence of active graft versus host disease and at least 84 days must have elapsed after transplant or stem cell infusion.
  • Patients undergoing a major surgical procedure or laparoscopic procedure are eligible for enrollment after at least 28 days of the procedure, 14 days after an open biopsy.
  • Patients undergoing a major surgical procedure, laparoscopic procedure or open biopsy are eligible for enrollment after at least 28 days of the procedure
  • Central line placement or subcutaneous port placement is not considered major surgery.
  • Core biopsy within 7 days prior to enrollment
  • Fine needle aspirate within 7 days prior to enrollment
  • Surgical or other wounds must be adequately healed prior to enrollment
  • Have received at least one front line treatment regimen for the treatment of their malignancy - on the Irinotecan combination arm, patients may have received prior Irinotecan
  • Have adequate organ and marrow function on first day of study treatment as follows:
  • For single agent 9-ING-41: ANC ≥ 500/mm3 For 9-ING-41 plus Irinotecan: ANC ≥ 1000/mm3
  • For single agent 9-ING-41: Platelets ≥ 50,000/mm3 For 9-ING-41 plus Irinotecan: Platelets ≥ 100,000/mm3
  • Hemoglobin ≥ 8 g/dL
  • Bilirubin ≤ 1.5 mg/dL
  • Alanine aminotransferase (ALT) ≤ 5.0 x upper limit of normal (ULN) unless elevation considered due to disease
  • Aspartate transaminase (AST) ≤ 5.0 x ULN unless elevation considered due to disease
  • Serum amylase and lipase ≤ 1.5 x ULN unless elevation considered due to disease
  • Creatinine clearance or radioisotope GFR ≥ 70 ml/min/1.73m2 or a serum creatinine based on age/gender as follows:
  • Age Maximum Serum Creatinine (mg/dL) Maximum Serum Creatinine (mg/dL) Male Female 1 month to <6 months 0.4 0.4 6 months to <1 year 0.5 0.5 1 to <2 years 0.6 0.6 2 to <6 years 0.8 0.8 6 to <10 years 1 1 10 to <13 years 1.2 1.2 13 to <16 years 1.5 1.4
  • ≥ 16 years 1.7 1.4
  • Pregnancy tests must be obtained in girls who are post-menarchal. Girls of childbearing potential must have a negative baseline blood or urine pregnancy test within 72 hours of first study therapy. Patients of childbearing potential must agree to use hormonal or barrier birth control with spermicidal gel, or total abstinence to avoid pregnancy for the duration of study participation and in the following 100 days after discontinuation of study treatment (see Section 4.1.1).
  • All patients and/or their parents or legal guardians must sign a written informed consent. The investigational nature and objectives of the trial, the procedures and treatments involved and their attendant risks and discomforts, and potential alternative therapies will be carefully explained to the patient or the patient's parents or guardian if the patient is a child, and a signed informed consent and assent will be obtained according to institutional guidelines

Who cannot join

  • Patients who meet any of the following criteria will be excluded from trial entry:
  • Has hypersensitivity to any of the components of 9-ING-41 and/or Irinotecan or to the excipients used in their formulation
  • Has uncontrolled concurrent illness that would limit compliance with study requirements
  • Has clinically significant retinal disease
  • Has current malignancy other than the target malignancy with the exception of surgically treated local tumors or is currently receiving other anti-cancer therapies, including radiation.
  • Has not recovered from clinically significant toxicities as a result of prior anticancer therapy, except alopecia, infertility and ototoxicity. Recovery is defined as ≤ Grade 2 severity per Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 (v5.0)
Show all 9Show fewer
  • Is pregnant or lactating
  • Has received a prior solid organ transplantation
  • Is receiving any other investigational medicinal product or participating in another interventional clinical trial

Trial locations and contacts

9 sites in 1 country.

9 sites in 1 country

United States9 sites

  • Mott Children's Hospital

    Ann Arbor, Michigan, 48109

  • Children's Hospital Colorado

    Aurora, Colorado, 80045

  • Levine Cancer Center

    Charlotte, North Carolina, 28204

  • University of Chicago

    Chicago, Illinois, 60637

  • Duke Children's Hospital and Health Center, Duke University Medical Center

    Durham, North Carolina, 27708

  • Texas Children's Hospital

    Houston, Texas, 77030

  • Brown University

    Providence, Rhode Island, 02912

  • University of California, San Francisco

    San Francisco, California, 94158-2549

  • Seattle Children's Research Institute

    Seattle, Washington, 98101

Other trials in United States

About this study

Official title: Phase 1 Study of 9-ING-41, a Glycogen Synthase Kinase 3 Beta (GSK 3β) Inhibitor, as a Single Agent or With Irinotecan, Irinotecan Plus Temozolomide, or With Cyclophosphamide Plus Topotecan in Pediatric Patients With Refractory Malignancies.

9-ING-41 has anti-cancer clinical activity with no significant toxicity in adult patients. This Phase 1 study will study its efficacy in paediatric patients with advanced malignancies.

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 and clinical anticancer activity. In the ongoing Actuate 1801 study in a cohort of over 90 patients with advanced refractory malignancies, 9-ING-41 has exhibited no significant toxicity, including no myelosuppression, and significant anti-tumor activity. 9-ING-41 also has significant pre-clinical ability to reverse pathologic fibrosis in multiple models of pulmonary and pleural fibrosis. 9-ING-41 is very highly active against neuroblastoma in diverse pre-clinical models. This Phase 1 study is designed to evaluate the safety and efficacy of 9-ING-41, as a single agent or in combination with irinitecan, in paediatric patients with advanced malignancies and thus to establish the recommended Phase 2 dose (RP2D) for further paediatric patient studies.

Being tested
9-ING-41, Irinotecan, Temozolomide, Cyclophosphamide, Topotecan
Keywords
9-ING-41, GSK3beta, Glycogen Synthase Kinase 3 Beta inhibitor, ATR/Chk1
Medical subject headings
Neoplasms, Neuroblastoma, Meningioma, Diffuse Intrinsic Pontine Glioma

What participants receive

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

  • 9-ING-41Drug

    Also called 9-ING-41 COMPOUND

    9-ING-41 will be administered by intravenous infusion twice weekly at an initial dose of 9.3 mg/kg. Cycle duration is 21 days.

  • IrinotecanDrug

    Also called CPT-11

    Irinotecan 50 mg/m2/day administered over 90 minutes IV on days 1-5 every 21 days.

  • TemozolomideDrug

    Also called Temodar

    Temozolomide will be administered at a dose of 100 mg/m2/dose by mouth on Days 1 through 5 of a 21 day cycle.

  • CyclophosphamideDrug

    Also called Cyclophosphamide IV

    Cyclophosphamide 400 mg/m2/dose administered intravenously over 30 min on Days 1 through 5 of a 21 day cycle.

  • TopotecanDrug

    Also called Topotecan IV

    Topotecan 1.2 mg/m2/dose administered intravenously over 30 min once on Days 1 through 5 of a 21 day cycle.

Study groups in NCT04239092
Study groupRoleWhat they receive
9-ING-41Experimental9-ING-41 will be administered by intravenous infusion twice weekly at an initial dose of 9.3 mg/kg. Cycle duration is 21 days.
Receives: Drug: 9-ING-41
9-ING-41 plus IrinotecanExperimental9-ING-41 will be administered by intravenous infusion twice weekly at an initial dose of 9.3 mg/kg. Irinotecan will be administered at a dose of 50 mg/m2/day over 90 minutes IV on days 1-5 every 21 days (cycle duration is 21 days).
Receives: Drug: 9-ING-41; Drug: Irinotecan
9-ING-41 plus Irinotecan plus TemozolomideExperimental9-ING-41 will be administered by intravenous infusion twice weekly at an initial dose of 9.3 mg/kg. Irinotecan will be administered at a dose of 50 mg/m2/day over 90 minutes IV on days 1-5 every 21 days. Temozolomide will be administered at a dose of 100 mg/m2/dose by mouth on Days 1 through 5 ((cycle duration is 21 days).
Receives: Drug: 9-ING-41; Drug: Irinotecan; Drug: Temozolomide
9-ING-41 plus Cyclophosphamide plus TopotecanExperimentalCyclophosphamide 400 mg/m2/dose administered intravenously over 30 min on Days 1 through 5. Topotecan 1.2 mg/m2/dose administered intravenously over 30 min once on Days 1 through 5. 9-ING-41 intravenous infusion twice weekly (cycle duration is 21 days).
Receives: Drug: 9-ING-41; Drug: Cyclophosphamide; Drug: Topotecan

What is being measured

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

  1. Number of participants with treatment-related adverse events as assessed by CTCAE v5

    The standard assessments used to assign a score to any affected organ system as per the NCI CTCAE 5 will be conduced at each protocol-specified timepoint.

    Measured: 3-12 months

Timeline

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

  1. First posted23 Jan 2020
  2. Study start5 Jun 2020
  3. Primary completion7 Jul 2025
  4. Study completion7 Jul 2025

Why it stopped: The decision to conclude study was made to optimize the clinical study design and protocol to further evaluate the safety profile of elraglusib (9-ING-41) in pediatric and adult patients with refractory Ewings Sarcoma.

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 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Model description
Patients will received either single agent 9-ING-41 or 9-ING-41 plus Irinotecan or 9-ING-41 plus Irinotecan plus Temozolomide or 9-ING-41 plus Cyclophosphamide plus Topotecan
Masking
None (open label)
Enrolment
40 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04239092
Sponsor's protocol ID
1902
Status last verified
Jul 2025
First submitted
20 Jan 2020
Last updated
17 Jul 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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

  • 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

  • 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

  • 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 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

  • 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

  • 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

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing 9-ING-41, Irinotecan and Temozolomide in people with Refractory Cancer and Refractory Neoplasm, run by Actuate Therapeutics Inc. at 9 sites in United States.

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 34 inclusion and 9 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: stopped early, as of the sponsor's last update on 17 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in United States. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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

Are results available for this study?

The study was stopped early (reason given: The decision to conclude study was made to optimize the clinical study design and protocol to further evaluate the safety profile of elraglusib (9-ING-41) in pediatric and adult patients with refractory Ewings Sarcoma.). Results are not available in the source record.

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?

Number of participants with treatment-related adverse events as assessed by CTCAE v5 (time frame: 3-12 months). 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 NCT04239092, which also lists 10 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 17 Jul 2025.

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