Clinical Trials /

A Phase 2 Study of 9-ING-41Combined With Chemotherapy in Adolescents and Adults With Advanced Sarcomas

NCT04906876

Description:

9-ING-41 in combination with gemcitabine and docetaxel will lead to sustained disease control and/or increase the rates of objective response in patients with unresectable or metastatic soft tissue and bone sarcomas. This is an open label, two-stratum, phase 2 clinical trial evaluating the efficacy of 9-ING-41 in combination with gemcitabine/docetaxel in patients ≥10 years of age with advanced sarcoma. Stratum A: Patients with advanced soft tissue sarcoma previously treated with 0-3 prior lines of systemic therapy will receive 9-ING-41 twice weekly with gemcitabine on days 1 and 8 and docetaxel on day 8 of a 21-day cycle until disease progression or unacceptable toxicity. Stratum B: Patients with relapsed or refractory bone sarcoma previously treated with at least one line of systemic therapy will receive 9-ING-41 twice weekly with gemcitabine on days 1 and 8 and docetaxel on day 8 of a 21-day cycle until disease progression or unacceptable toxicity. Disease response assessment will be performed every 2 cycles (6 weeks) for the first 8 cycles (24 weeks), then every 12 weeks thereafter.

Related Conditions:
  • Angiosarcoma
  • Ewing Sarcoma
  • Leiomyosarcoma
  • Liposarcoma
  • Myxofibrosarcoma
  • Osteosarcoma
  • Rhabdomyosarcoma
  • Sarcoma, NOS
  • Spindle Cell Sarcoma
  • Synovial Sarcoma
  • Undifferentiated Pleomorphic Sarcoma
Recruiting Status:

Withdrawn

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Phase 2 Study of 9-ING-41Combined With Chemotherapy in Adolescents and Adults With Advanced Sarcomas
  • Official Title: A Phase 2 Study of 9-ING-41, a Glycogen Synthase Kinase-3 Beta (GSK-3β) Inhibitor, Combined With Chemotherapy in Adolescents and Adults With Advanced Sarcomas

Clinical Trial IDs

  • ORG STUDY ID: BrUOG 398
  • NCT ID: NCT04906876

Conditions

  • Sarcoma
  • Soft Tissue Sarcoma
  • Metastatic Sarcoma
  • Undifferentiated Pleomorphic Sarcoma
  • Myxofibrosarcoma
  • Leiomyosarcoma
  • Liposarcoma
  • Angiosarcoma
  • Synovial Sarcoma
  • Rhabdomyosarcoma
  • Spindle Cell Sarcoma
  • High Grade Sarcoma
  • Bone Sarcoma

Interventions

DrugSynonymsArms
GemcitabineStratum A: Soft Tissue Sarcoma
DocetaxelStratum A: Soft Tissue Sarcoma
9-ING-41Stratum A: Soft Tissue Sarcoma

Purpose

9-ING-41 in combination with gemcitabine and docetaxel will lead to sustained disease control and/or increase the rates of objective response in patients with unresectable or metastatic soft tissue and bone sarcomas. This is an open label, two-stratum, phase 2 clinical trial evaluating the efficacy of 9-ING-41 in combination with gemcitabine/docetaxel in patients ≥10 years of age with advanced sarcoma. Stratum A: Patients with advanced soft tissue sarcoma previously treated with 0-3 prior lines of systemic therapy will receive 9-ING-41 twice weekly with gemcitabine on days 1 and 8 and docetaxel on day 8 of a 21-day cycle until disease progression or unacceptable toxicity. Stratum B: Patients with relapsed or refractory bone sarcoma previously treated with at least one line of systemic therapy will receive 9-ING-41 twice weekly with gemcitabine on days 1 and 8 and docetaxel on day 8 of a 21-day cycle until disease progression or unacceptable toxicity. Disease response assessment will be performed every 2 cycles (6 weeks) for the first 8 cycles (24 weeks), then every 12 weeks thereafter.

Trial Arms

NameTypeDescriptionInterventions
Stratum A: Soft Tissue SarcomaExperimentalPatients with advanced soft tissue sarcoma previously treated with 0-3 prior lines of systemic therapy will receive 15 mg/kg 9-ING-41 twice weekly with 900 mg/m2 gemcitabine on days 1 and 8 and 75 mg/m2 docetaxel on day 8 of a 21-day cycle until disease progression or unacceptable toxicity.
  • Gemcitabine
  • Docetaxel
  • 9-ING-41
Stratum B: Bone SarcomaExperimentalPatients with relapsed or refractory bone sarcoma previously treated with at least one line of systemic therapy will receive 15 mg/kg 9-ING-41 twice weekly with 900 mg/m2 gemcitabine on days 1 and 8 and 75 mg/m2 docetaxel on day 8 of a 21-day cycle until disease progression or unacceptable toxicity.
  • Gemcitabine
  • Docetaxel
  • 9-ING-41

Eligibility Criteria

        Inclusion Criteria:

          -  Stratum A: Patients must have histologically confirmed grade 2 or 3 soft tissue
             sarcoma that is locally advanced and unresectable, or metastatic, consisting of one of
             the following subtypes: undifferentiated pleomorphic sarcoma (malignant fibrous
             histiocytoma), myxofibrosarcoma, leiomyosarcoma, liposarcoma (excluding
             well-differentiated), angiosarcoma, synovial sarcoma, rhabdomyosarcoma, spindle cell
             sarcoma and high-grade sarcoma NOS.

          -  Stratum B: Patients must have histologically confirmed bone sarcoma that is relapsed
             or refractory following front-line therapy consisting of one of the following
             subtypes: osteosarcoma and Ewing sarcoma.

          -  Patients must have at least one site of measurable disease by RECIST 1.1. See Section
             12 (Measurement of Effect) for the evaluation of measurable disease.

          -  Stratum A: No more than three prior lines of systemic therapy. Of note,
             anthracycline-based chemotherapy is generally considered first-line therapy.
             Previously untreated patients may be enrolled at the discretion of the treating
             investigator.

          -  Stratum B: At least one prior line of systemic therapy.

          -  Age ≥10 years.

          -  Lansky score ≥50 for patients <16 years or ECOG performance status ≤2 for patients ≥16
             years (Karnofsky ≥50%, see Appendix A).

          -  Life expectancy of greater than 12 weeks.

          -  Patients must have adequate organ and marrow function as defined below:

               -  Hemoglobin ≥8 g/dl

               -  absolute neutrophil count ≥1,000/mcL

               -  platelets ≥100,000/mcL (transfusion independent)

               -  total bilirubin ≤1.5x institutional upper limit of normal (ULN) (<3.0 mg/dL and
                  direct bilirubin <1.5 mg/dL if documented Gilbert's syndrome)

               -  AST(SGOT)/ALT(SGPT) ≤3x institutional ULN (≤ 5 x ULN if liver metastases present)

               -  creatinine ≤1.5x institutional ULN OR

               -  glomerular filtration rate (GFR) ≥50 mL/min/1.73 m2

               -  PT/INR ≤1.5x institutional ULN

               -  Amylase and lipase ≤1.5x institutional ULN

          -  Washout period prior to Cycle 1, Day 1:

               -  ≥ 21 days since last dose of chemotherapy, immunotherapy, or therapeutic
                  radiation treatment.

               -  ≥ 28 days since last tyrosine kinase inhibitor (or 5 half-lives, whichever is
                  shorter).

               -  ≥ 7 days since last focal palliative radiation treatment.

               -  ≥ 28 days since major surgical procedure.

          -  Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral
             therapy with undetectable viral load within 6 months are eligible for this trial.

          -  For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral
             load must be undetectable on suppressive therapy, if indicated.

          -  Patients with a history of hepatitis C virus (HCV) infection must have been treated
             and cured. For patients with HCV infection who are currently on treatment, they are
             eligible if they have an undetectable HCV viral load.

          -  Women of child-bearing potential must have a negative serum or urine pregnancy test at
             registration and within 7 days of first study therapy.

          -  The effects of 9-ING-41 on the developing human fetus are unknown. For this reason and
             because other therapeutic agents used in this trial are known to be teratogenic, women
             of child-bearing potential and men must agree to use adequate contraception (hormonal
             or barrier method of birth control; abstinence) prior to study entry and for the
             duration of study participation. Should a woman become pregnant or suspect she is
             pregnant while she or her partner is participating in this study, she should inform
             her treating physician immediately. Women may not be breastfeeding during study
             participation. Men treated or enrolled on this protocol must also agree to use
             adequate contraception prior to the study, for the duration of study participation,
             and 90 days after completion of 9-ING-41 administration.

          -  Patients must agree to provide tumor tissue, either fresh or archival specimen of
             primary tumor and/or metastatic lesion. If tumor tissue is not available, then discuss
             with principal investigator.

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

        Exclusion Criteria:

          -  Patients with sarcoma histologies other than those listed above will be excluded.

          -  Prior treatment with 9-ING-41, gemcitabine, or docetaxel.

          -  Patients who have not recovered from adverse events due to prior anti-cancer therapy
             (i.e., have residual toxicities > Grade 1) with the exception of alopecia.

          -  Patients who are receiving any other investigational agents for treatment of their
             sarcoma.

          -  Patients who are pregnant or lactating.

          -  Patients with untreated brain or meningeal metastases. Subjects with history of
             metastases are eligible provided they do not require ongoing steroid treatment and
             have shown clinical and radiographic stability for at least 14 days after definitive
             therapy.

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to 9-ING-41, gemcitabine, docetaxel, or other agents used in study.

          -  Patients with uncontrolled intercurrent illness including, but not limited to, ongoing
             or active infection, symptomatic congestive heart failure, unstable angina pectoris,
             cardiac arrhythmia, or psychiatric illness/social situations that would limit
             compliance with study requirements.

          -  Has had a previous (within 2 years) or has a current malignancy other than the target
             cancer with the exception of curatively treated local tumors including carcinoma in
             situ of the breast or cervix, basal or squamous cell carcinoma of the skin, or
             prostate cancer with Gleason Grade < 6 and prostate-specific antigen within normal
             range.

          -  Has any medical and/or social condition that, in the opinion of the investigator would
             preclude study participation.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:10 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Disease Control Rate
Time Frame:Approximately 24 weeks
Safety Issue:
Description:To determine the Disease Control Rate (DCR = Complete Response [CR] + Partial Response [PR] + Stable Disease [SD] at 6 months) of 9-ING-41 in combination with gemcitabine and docetaxel in advanced sarcoma.

Secondary Outcome Measures

Measure:Progression Free Survival
Time Frame:From start of protocol therapy, approximately 5 years
Safety Issue:
Description:To determine the activity of 9-ING-41 with chemotherapy by assessing progression free survival (PFS).

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Withdrawn
Lead Sponsor:Brown University

Last Updated

July 28, 2021