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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04239092
Recruitment Status : Recruiting
First Posted : January 23, 2020
Last Update Posted : June 9, 2020
Sponsor:
Collaborator:
Developmental Therapeutics Consortium
Information provided by (Responsible Party):
Actuate Therapeutics Inc.

Tracking Information
First Submitted Date  ICMJE January 20, 2020
First Posted Date  ICMJE January 23, 2020
Last Update Posted Date June 9, 2020
Actual Study Start Date  ICMJE June 5, 2020
Estimated Primary Completion Date April 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 20, 2020)
Number of participants with treatment-related adverse events as assessed by CTCAE v5 [ Time Frame: 3-12 months ]
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 9-ING-41 in Pediatric Patients With Refractory Malignancies.
Official Title  ICMJE Phase 1 Study of 9-ING-41, a Glycogen Synthase Kinase 3 Beta (GSK 3β) Inhibitor, as a Single Agent or With Irinotecan in Pediatric Patients With Refractory Malignancies.
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.
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Patients will receive either single agent 9-ING-41 or 9-ING-41 plus Irinotecan
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Refractory Cancer
  • Refractory Neoplasm
  • Cancer Pediatric
  • Refractory Tumor
  • Pediatric Cancer
  • Pediatric Brain Tumor
  • Neuroblastoma
  • Neuroblastoma Recurrent
  • Pediatric Lymphoma
  • Pediatric Meningioma
Intervention  ICMJE
  • Drug: 9-ING-41
    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.
    Other Name: 9-ING-41 COMPOUND
  • Drug: Irinotecan
    Irinotecan 50 mg/m2/day administered over 90 minutes IV on days 1-5 every 21 days.
    Other Name: CPT-11
Study Arms  ICMJE
  • Experimental: 9-ING-41
    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.
    Intervention: Drug: 9-ING-41
  • Experimental: 9-ING-41 plus Irinotecan
    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).
    Interventions:
    • Drug: 9-ING-41
    • Drug: Irinotecan
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 20, 2020)
48
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2021
Estimated Primary Completion Date April 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

Patients must meet ALL the following criteria to be eligible for this study:

  1. Age < 22 years of age
  2. 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.
  3. 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)
  4. Have current disease state for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life
  5. Have Performance Level: Karnofsky ≥ 50% for patients >16 years of age and Lansky ≥50 for patients ≤16 years of age
  6. 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
  7. 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
  8. 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
  9. 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

  10. 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).
  11. 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

Exclusion Criteria:

Patients who meet any of the following criteria will be excluded from trial entry:

  1. Has hypersensitivity to any of the components of 9-ING-41 and/or Irinotecan or to the excipients used in their formulation
  2. Has uncontrolled concurrent illness that would limit compliance with study requirements
  3. Has clinically significant retinal disease
  4. 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.
  5. 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)
  6. Is pregnant or lactating
  7. Has received a prior solid organ transplantation
  8. Is receiving any other investigational medicinal product or participating in another interventional clinical trial
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 22 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Francis Giles, MD +1 2817961852 fgiles@actuatetherapeutics.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04239092
Other Study ID Numbers  ICMJE 1902
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Actuate Therapeutics Inc.
Study Sponsor  ICMJE Actuate Therapeutics Inc.
Collaborators  ICMJE Developmental Therapeutics Consortium
Investigators  ICMJE
Study Director: Ludimila Cavalcante, MD Actuate Therapeutics Inc.
PRS Account Actuate Therapeutics Inc.
Verification Date June 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP