Phase 2 Study of 9-ING-41 With Chemotherapy in Sarcoma

NCT05116800 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: Br 398
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

Brief Summary

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. 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.

Conditions

Soft Tissue Sarcoma; Undifferentiated Pleomorphic Sarcoma; Myxofibrosarcoma; Leiomyosarcoma; Liposarcoma; Angiosarcoma; Synovial Sarcoma; Rhabdomyosarcoma; Spindle Cell Sarcoma; High Grade Sarcoma; Bone Sarcoma; Osteosarcoma; Ewing Sarcoma of Bone

Outcome Measures

Primary Outcomes (1)

• Disease Control Rate

  To determine the Disease Control Rate (DCR = Complete Response \[CR\] + Partial Response \[PR\] + Stable Disease \[SD\] at 24 weeks) of 9-ING-41 in combination with gemcitabine and docetaxel in advanced sarcoma.

  Approximately 24 weeks

Secondary Outcomes (1)

• Progression Free Survival

  From start of protocol therapy, approximately 5 years

Study Arms (2)

Stratum A: Soft Tissue Sarcoma

EXPERIMENTAL

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.

Drug: Gemcitabine; Drug: 9-ING-41; Drug: Docetaxel

Stratum B: Bone Sarcoma

EXPERIMENTAL

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.

Drug: Gemcitabine; Drug: 9-ING-41; Drug: Docetaxel

Interventions

Gemcitabine DRUG

Patients will receive 9.3 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.

Stratum A: Soft Tissue Sarcoma; Stratum B: Bone Sarcoma

9-ING-41 DRUG

Patients will receive 9.3 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.

Stratum A: Soft Tissue Sarcoma; Stratum B: Bone Sarcoma

Docetaxel DRUG

Patients will receive 9.3 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.

Stratum A: Soft Tissue Sarcoma; Stratum B: Bone Sarcoma

Eligibility Criteria

• Age: 10 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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) ≤2.5x institutional ULN (≤ 5 x ULN if liver metastases present)
• creatinine ≤1.5x institutional ULN OR

You may not qualify if:

• 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.

Sponsors & Collaborators

• Brown University: lead
• Actuate Therapeutics Inc.: collaborator

Study Sites (2)

Hasbro Children's Hospital

Providence, Rhode Island, 02903, United States

Location

Lifespan Cancer Insitute

Providence, Rhode Island, 02903, United States

Location

MeSH Terms

Conditions

Sarcoma; Histiocytoma, Malignant Fibrous; Dermatofibrosarcoma; Leiomyosarcoma; Liposarcoma; Hemangiosarcoma; Sarcoma, Synovial; Rhabdomyosarcoma; Bone Neoplasms; Osteosarcoma

Interventions

Gemcitabine; 3-(5-fluorobenzofuran-3-yl)-4-(5-methyl-5H-(1,3)dioxolo(4,5-f)indol-7-yl)-pyrrole-2,5-dione; Docetaxel

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Histiocytoma; Neoplasms, Fibrous Tissue; Neoplasms, Connective Tissue; Fibrosarcoma; Neoplasms, Muscle Tissue; Neoplasms, Adipose Tissue; Neoplasms, Vascular Tissue; Myosarcoma; Neoplasms by Site; Bone Diseases; Musculoskeletal Diseases; Neoplasms, Bone Tissue

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Bradley D DeNardo, MD

  Brown University

  PRINCIPAL INVESTIGATOR

• Galina G Lagos, MD

  Lifespan Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 2, 2021
• First Posted: November 11, 2021
• Study Start: March 1, 2022
• Primary Completion: August 1, 2025
• Study Completion (Estimated): August 1, 2030
• Last Updated: December 7, 2021

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)