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

Primary Purpose

Sarcoma, Soft Tissue Sarcoma, Metastatic Sarcoma

Status
Withdrawn
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Gemcitabine
Docetaxel
9-ING-41
Sponsored by
Brown University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Sarcoma

Eligibility Criteria

10 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Hasbro Children's Hospital
  • Lifespan Cancer Insitute

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Stratum A: Soft Tissue Sarcoma

Stratum B: Bone Sarcoma

Arm Description

Patients 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.

Patients 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.

Outcomes

Primary Outcome Measures

Disease Control Rate
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

Progression Free Survival
To determine the activity of 9-ING-41 with chemotherapy by assessing progression free survival (PFS).

Full Information

First Posted
May 21, 2021
Last Updated
July 26, 2021
Sponsor
Brown University
Collaborators
Actuate Therapeutics Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT04906876
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
Study Type
Interventional

2. Study Status

Record Verification Date
July 2021
Overall Recruitment Status
Withdrawn
Why Stopped
IND withdrawn
Study Start Date
September 2021 (Anticipated)
Primary Completion Date
July 2022 (Anticipated)
Study Completion Date
July 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Brown University
Collaborators
Actuate Therapeutics Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sarcoma, Soft Tissue Sarcoma, Metastatic Sarcoma, Undifferentiated Pleomorphic Sarcoma, Myxofibrosarcoma, Leiomyosarcoma, Liposarcoma, Angiosarcoma, Synovial Sarcoma, Rhabdomyosarcoma, Spindle Cell Sarcoma, High Grade Sarcoma, Bone Sarcoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Stratum A: Soft Tissue Sarcoma
Arm Type
Experimental
Arm Description
Patients 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.
Arm Title
Stratum B: Bone Sarcoma
Arm Type
Experimental
Arm Description
Patients 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.
Intervention Type
Drug
Intervention Name(s)
Gemcitabine
Intervention Description
Gemcitabine as a 90-minute IV infusion
Intervention Type
Drug
Intervention Name(s)
Docetaxel
Intervention Description
Docetaxel as a 60-minute IV infusion
Intervention Type
Drug
Intervention Name(s)
9-ING-41
Intervention Description
9-ING-41 as an IV infusion over 1-4 hours twice weekly
Primary Outcome Measure Information:
Title
Disease Control Rate
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.
Time Frame
Approximately 24 weeks
Secondary Outcome Measure Information:
Title
Progression Free Survival
Description
To determine the activity of 9-ING-41 with chemotherapy by assessing progression free survival (PFS).
Time Frame
From start of protocol therapy, approximately 5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
10 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bradley DeNardo, MD
Organizational Affiliation
Brown University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Don S Dizon, MD
Organizational Affiliation
Lifespan Cancer Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hasbro Children's Hospital
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02903
Country
United States
Facility Name
Lifespan Cancer Insitute
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02903
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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