Clinical Trials /

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

NCT04239092

Description:

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.

Related Conditions:
  • Cancer
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: 9-ING-41 in Pediatric Patients With Refractory Malignancies.
  • 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 in Pediatric Patients With Refractory Malignancies.

Clinical Trial IDs

  • ORG STUDY ID: 1902
  • NCT ID: NCT04239092

Conditions

  • Refractory Cancer
  • Refractory Neoplasm
  • Cancer Pediatric
  • Refractory Tumor
  • Pediatric Cancer
  • Pediatric Brain Tumor
  • Neuroblastoma
  • Neuroblastoma Recurrent
  • Pediatric Lymphoma
  • Pediatric Meningioma

Interventions

DrugSynonymsArms
9-ING-419-ING-41 COMPOUND9-ING-41
IrinotecanCPT-119-ING-41 plus Irinotecan

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
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.
  • 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).
  • 9-ING-41
  • Irinotecan

Eligibility Criteria

        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 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.

          4. 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)

          5. Is pregnant or lactating

          6. Has received a prior solid organ transplantation

          7. Is receiving any other investigational medicinal product or participating in another
             interventional clinical trial
      
Maximum Eligible Age:22 Years
Minimum Eligible Age:N/A
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of participants with treatment-related adverse events as assessed by CTCAE v5
Time Frame:3-12 months
Safety Issue:
Description: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.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Actuate Therapeutics Inc.

Trial Keywords

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

Last Updated

January 20, 2020