Clinical Trials /

9-ING-41 Plus Carboplatin in Patients With Advanced, Metastatic Salivary Gland Carcinoma

NCT04832438

Description:

9-ING-41 is a small molecule potent selective GSK-3β inhibitor with antitumor activity. This study investigates 9-ING-41 in combination with carboplatin chemotherapy in patients with incurable, recurrent or metastatic salivary gland carcinomas (SGC). Patients with advanced SGC (including all histologic subtypes and adenoid cystic carcinoma [ACC]) will receive 9-ING-41 intravenously (IV) along with carboplatin IV at standard dosing together on Day 1, and 9-ING-41 alone on Day 4 of a 21-day cycle. Participants will be enrolled to two histologic cohorts: Cohort 1 will be comprised of those with ACC, and Cohort 2 will include patients with non-ACC SGC (or all other salivary gland cancer histologies). Treatment will continue until progression of disease, death, or discontinuation of therapy for any reason.

Related Conditions:
  • Salivary Gland Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 9-ING-41 Plus Carboplatin in Patients With Advanced, Metastatic Salivary Gland Carcinoma
  • Official Title: Phase 2 Study of 9-ING-41, a Glycogen Synthase Kinase 3 Beta (GSK 3β) Inhibitor, Plus Carboplatin in Patients With Advanced, Metastatic Salivary Gland Carcinoma

Clinical Trial IDs

  • ORG STUDY ID: 2102
  • NCT ID: NCT04832438

Conditions

  • Salivary Gland Carcinoma
  • Adenoid Cystic Carcinoma
  • Salivary Gland Cancer
  • Salivary Gland Neoplasms

Interventions

DrugSynonymsArms
9-ING-419-ING-41 plus carboplatin
Carboplatin9-ING-41 plus carboplatin

Purpose

9-ING-41 is a small molecule potent selective GSK-3β inhibitor with antitumor activity. This study investigates 9-ING-41 in combination with carboplatin chemotherapy in patients with incurable, recurrent or metastatic salivary gland carcinomas (SGC). Patients with advanced SGC (including all histologic subtypes and adenoid cystic carcinoma [ACC]) will receive 9-ING-41 intravenously (IV) along with carboplatin IV at standard dosing together on Day 1, and 9-ING-41 alone on Day 4 of a 21-day cycle. Participants will be enrolled to two histologic cohorts: Cohort 1 will be comprised of those with ACC, and Cohort 2 will include patients with non-ACC SGC (or all other salivary gland cancer histologies). Treatment will continue until progression of disease, death, or discontinuation of therapy for any reason.

Detailed Description

      9-ING-41 is a small molecule potent selective GSK-3β inhibitor with antitumor activity. It
      acts through downregulation of NF-κB and decreases the expression NF-κB target genes 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. 9-ING-41 may also function as an immune modulatory agent by
      decreasing checkpoint expression and enhancement of T-cell / NK-cell effector function. This
      is a phase 2, open-label, non-randomized, single institution study investigating the novel
      glycogen synthase kinase-3 beta (GSK-3β) inhibitor 9-ING-41 in combination with carboplatin
      chemotherapy in patients with incurable, recurrent or metastatic salivary gland carcinomas
      (SGC). The safety of this combination has been established in the Actuate 1801 study.
      Thirty-one evaluable patients with advanced SGC (including all histologic subtypes and
      adenoid cystic carcinoma [ACC]) will receive 9-ING-41 intravenously (IV) along with
      carboplatin IV at standard dosing together on Day 1, and 9-ING-41 alone on Day 4 of a 21-day
      cycle. Participants will be enrolled to two histologic cohorts: Cohort 1 will be comprised of
      those with ACC, and Cohort 2 will include patients with non-ACC SGC (or all other salivary
      gland cancer histologies). Treatment will continue until progression of disease, death, or
      discontinuation of therapy for any reason.

      The primary aim of the study is to assess the overall response rate (ORR) as defined by
      RECIST v1.1 in the overall study population (including both Cohorts 1 and 2). Secondary aims
      include assessing progression-free survival (PFS), overall survival (OS), determining safety
      and tolerability, measuring patient-reported quality of life metrics, and correlating
      efficacy with molecular and immunologic predictors of response. We hypothesize that the novel
      combination of a GSK-3β inhibitor with carboplatin chemotherapy will result in an ORR of 25%
      or greater in this patient population where no approved therapies have been established.
    

Trial Arms

NameTypeDescriptionInterventions
9-ING-41 plus carboplatinExperimentalPatients will receive 9-ING-41 (15 mg/kg IV on Day 1 and Day 4) in addition to carboplatin (AUC 5 IV on Day 1) each of a 21-day cycle
  • 9-ING-41
  • Carboplatin

Eligibility Criteria

        Inclusion Criteria:

          1. Participants must have histologically confirmed salivary gland carcinoma (any
             histologic subtype, including ACC) with evidence of recurrent, metastatic or advanced,
             unresectable disease.

          2. Willing to provide tumor tissue from a diagnostic biopsy or prior surgery.

          3. Age 18 years or older

          4. ECOG performance status 0-2 (see Appendix A)

          5. Participant must have organ and marrow function as defined below within 14 days prior
             to study registration:

               -  leukocytes ≥ 3,000/mcL

               -  absolute neutrophil count ≥ 500/mcL

               -  hemoglobin ≥ 8.5 g/dL

               -  platelets ≥ 75,000/mcL

               -  total bilirubin ≤ 2.0 g/dL

               -  AST(SGOT)/ALT(SGPT) ≤ 2.5× institutional upper limit of normal

               -  creatinine within normal institutional limits OR

               -  creatinine clearance ≥50 mL/min/1.73 m2 for participants with creatinine levels
                  above institutional normal

          6. Participants must have documentation of a new or progressive lesion on a radiologic
             imaging study performed within 12 months prior to study registration (progression of
             disease over any interval is allowed) and/or new or worsening disease-related symptoms
             within 12 months prior to study registration.

          7. Participants must have at least one RECIST v1.1 measurable non-CNS based lesion.

          8. Prior systemic therapy: At least 2 weeks must have elapsed since the end of prior
             chemotherapy, biological agents (3 weeks for anti-cancer monoclonal antibody
             containing regimens) or any investigational drug product, with adequate recovery of
             treatment-related toxicity to NCI CTCAE Version 5.0 grade ≤1 (or tolerable grade 2) or
             back to baseline (except for alopecia or neuropathy). Any number of prior therapies
             for recurrent/metastatic SGC are permitted (including prior carboplatin exposure).

          9. Ability to understand and the willingness to sign a written informed consent document.

         10. Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy
             test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to
             the start of study treatment.

         11. Men who are sexually active with WOCBP must agree to use any contraceptive method with
             a failure rate of less than 1% per year. Men who are sexually active with WOCBP will
             be instructed to adhere to contraception for a period of 90 days after the last dose
             of investigational product.

        Exclusion Criteria:

          1. Metastatic disease impinging on the spinal cord or threatening spinal cord
             compression. Patients that have had previous treatment of disease with impinging on
             the cord with either surgery or radiotherapy with clinical or radiographic evidence of
             response or stability are eligible.

          2. Participant has known active central nervous system (CNS) metastases and/or
             carcinomatous meningitis. Subjects with previously treated brain metastases may
             participate provided they are stable (without evidence of progression by imaging for
             at least four weeks prior to the first dose of trial treatment), and have no evidence
             of new or enlarging brain metastases.

          3. Concurrent administration of other cancer specific therapy or investigational agents
             during the course of this study is not allowed.

          4. Uncontrolled intercurrent illness including but not limited to ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac
             arrhythmia.

          5. Pregnant or lactating women.

          6. Has a known additional malignancy that is progressing or requires active treatment.
             Exceptions include: basal cell carcinoma of the skin or squamous cell carcinoma of the
             skin that has undergone potentially curative therapy or in situ cervical cancer, and
             low-risk prostate adenocarcinoma being managed with active surveillance. A history of
             another separate malignancy in remission without evidence of active disease in the
             last 2 years is permitted.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of evaluable patients with objective response as measured by RECIST version 1.1
Time Frame:3-24 months
Safety Issue:
Description:Response and progression will be evaluated in this study using the international Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1). Changes in the largest diameter (unidimensional measurement) of the tumor lesions and the shortest diameter in the case of malignant lymph nodes are used in the RECIST criteria.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Actuate Therapeutics Inc.

Trial Keywords

  • advanced
  • metastatic
  • 9-ING-41
  • carboplatin
  • refractory

Last Updated

April 8, 2021