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

NCT04239092 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: 1902
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 9

Brief 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.

Conditions

Refractory Cancer; Refractory Neoplasm; Cancer Pediatric; Refractory Tumor; Pediatric Cancer; Pediatric Brain Tumor; Neuroblastoma; Neuroblastoma Recurrent; Pediatric Lymphoma; Pediatric Meningioma; Diffuse Intrinsic Pontine Glioma

Keywords

9-ING-41; GSK3beta; Glycogen Synthase Kinase 3 Beta inhibitor; ATR/Chk1

Outcome Measures

Primary Outcomes (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.

  3-12 months

Study Arms (4)

9-ING-41

EXPERIMENTAL

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.

Drug: 9-ING-41

9-ING-41 plus Irinotecan

EXPERIMENTAL

9-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).

Drug: 9-ING-41; Drug: Irinotecan

9-ING-41 plus Irinotecan plus Temozolomide

EXPERIMENTAL

9-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).

Drug: 9-ING-41; Drug: Irinotecan; Drug: Temozolomide

9-ING-41 plus Cyclophosphamide plus Topotecan

EXPERIMENTAL

Cyclophosphamide 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).

Drug: 9-ING-41; Drug: Cyclophosphamide; Drug: Topotecan

Interventions

9-ING-41 DRUG

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.

Also known as: 9-ING-41 COMPOUND

9-ING-41; 9-ING-41 plus Cyclophosphamide plus Topotecan; 9-ING-41 plus Irinotecan; 9-ING-41 plus Irinotecan plus Temozolomide

Irinotecan DRUG

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

Also known as: CPT-11

9-ING-41 plus Irinotecan; 9-ING-41 plus Irinotecan plus Temozolomide

Temozolomide DRUG

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

Also known as: Temodar

9-ING-41 plus Irinotecan plus Temozolomide

Cyclophosphamide DRUG

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

Also known as: Cyclophosphamide IV

9-ING-41 plus Cyclophosphamide plus Topotecan

Topotecan DRUG

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

Also known as: Topotecan IV

9-ING-41 plus Cyclophosphamide plus Topotecan

Eligibility Criteria

• Age: Up to 22 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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)
• 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

Sponsors & Collaborators

• Actuate Therapeutics Inc.: lead

Study Sites (9)

University of California, San Francisco

San Francisco, California, 94158-2549, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Mott Children's Hospital

Ann Arbor, Michigan, 48109, United States

Location

Levine Cancer Center

Charlotte, North Carolina, 28204, United States

Location

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

Durham, North Carolina, 27708, United States

Location

Brown University

Providence, Rhode Island, 02912, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

Seattle Children's Research Institute

Seattle, Washington, 98101, United States

Location

Related Publications (10)

• 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.

  PMID: 24327518 RESULT

• 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.

  PMID: 27424289 RESULT

• 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.

  PMID: 28672195 RESULT

• 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.

  PMID: 29383130 RESULT

• 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.

  PMID: 29846250 RESULT

• 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.

  PMID: 31101621 RESULT

• 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.

  PMID: 31533931 RESULT

• 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.

  PMID: 31831767 RESULT

• 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.

  PMID: 31882719 RESULT

• 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.

  PMID: 28053024 RESULT

MeSH Terms

Conditions

Neoplasms; Neuroblastoma; Meningioma; Diffuse Intrinsic Pontine Glioma

Interventions

3-(5-fluorobenzofuran-3-yl)-4-(5-methyl-5H-(1,3)dioxolo(4,5-f)indol-7-yl)-pyrrole-2,5-dione; Irinotecan; Temozolomide; Cyclophosphamide; Topotecan

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Neoplasms, Vascular Tissue; Meningeal Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Nervous System Diseases; Glioma; Brain Stem Neoplasms; Infratentorial Neoplasms; Brain Neoplasms; Brain Diseases; Central Nervous System Diseases

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phosphoramides; Organophosphorus Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: January 20, 2020
• First Posted: January 23, 2020
• Study Start: June 5, 2020
• Primary Completion: July 7, 2025
• Study Completion: July 7, 2025
• Last Updated: July 17, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (9)