Clinical Trials /

A Trial of TTI-621 in Combination With Doxorubicin in Patients With Leiomyosarcoma

NCT04996004

Description:

Multi-center, open-label, Phase I/II dose escalation and expansion trial of TTI-621 in patients with unresectable or metastatic high-grade leiomyosarcoma.

Related Conditions:
  • Angiosarcoma
  • Dedifferentiated Liposarcoma
  • Epithelioid Sarcoma
  • Leiomyosarcoma
  • Myxofibrosarcoma
  • Undifferentiated Pleomorphic Sarcoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Trial of TTI-621 in Combination With Doxorubicin in Patients With Leiomyosarcoma
  • Official Title: A Phase I/II Study of TTI-621 in Combination With Doxorubicin in Patients With Unresectable or Metastatic High-Grade Leiomyosarcoma

Clinical Trial IDs

  • ORG STUDY ID: TTI-621-03
  • NCT ID: NCT04996004

Conditions

  • Leiomyosarcoma

Interventions

DrugSynonymsArms
TTI-621Dose Escalation
DoxorubicinDose Escalation

Purpose

Multi-center, open-label, Phase I/II dose escalation and expansion trial of TTI-621 in patients with unresectable or metastatic high-grade leiomyosarcoma.

Detailed Description

      This trial will be conducted in 2 phases: Phase I (Dose Escalation of TTI-621 in combination
      with doxorubicin) and Phase II (Dose Expansion of TTI-621 in combination with doxorubicin).

      Phase I (Dose Escalation of TTI-621 in combination with doxorubicin) will enroll patients
      with soft-tissue sarcomas including leiomyosarcoma, undifferentiated pleomorphic sarcoma,
      myxofibrosarcoma, dedifferentiated liposarcoma, angiosarcoma or epithelioid sarcoma

      Phase II (Dose Expansion of TTI-621 in combination with doxorubicin) will include 2 cohorts:
      Cohort A and Cohort B. The lower selected dose of TTI-621 will be studied in Cohort A while
      the higher dose of TTI-621 will be studied in Cohort B. Patients with leiomyosarcoma will be
      enrolled.
    

Trial Arms

NameTypeDescriptionInterventions
Dose EscalationExperimental
  • TTI-621
  • Doxorubicin
Dose Expansion Low Dose (Cohort A)Experimental
  • TTI-621
  • Doxorubicin
Dose Expansion High Dose (Cohort B)Experimental
  • TTI-621
  • Doxorubicin

Eligibility Criteria

        Key Inclusion Criteria:

          1. Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1.

          2. Histologically-confirmed high-grade soft tissue sarcoma that is metastatic or locally
             advanced and not amenable to curative treatment with surgery or radiation.

               1. In the Dose Escalation phase, indications will be limited to high-grade
                  leiomyosarcoma, undifferentiated pleomorphic sarcoma, myxofibrosarcoma,
                  dedifferentiated liposarcoma, angiosarcoma and epithelioid sarcoma

               2. In the Dose Expansion phase, indications will be limited to high-grade
                  leiomyosarcoma.

          3. Objective evidence of disease progression unless disease is newly-diagnosed.

          4. Measurable disease per RECIST v1.1 (expansion cohorts).

          5. Adequate organ and hematologic function.

          6. No more than 1 prior treatment regimen for advanced disease, which is limited to
             gemcitabine with docetaxel.

          7. Anthracycline-naïve.

          8. Patients who were treated with a prior chemotherapy regimen must have completed
             treatment at least three weeks before initiation of study treatment.

          9. All adverse events from prior treatment must be NCI CTCAE v5 Grade ≤ 1, except
             alopecia and stable neuropathy, which must have resolved to Grade ≤ 2 or baseline.

         10. Radiotherapy, including palliative radiotherapy, completed at least two weeks prior to
             treatment; palliative radiation to non-target lesions while on study is allowed.

        Key Exclusion Criteria:

          1. History of acute coronary syndromes.

          2. History of or current Class II, III, or IV heart failure.

          3. History or evidence of known CNS metastases or carcinomatous meningitis.

          4. Significant bleeding disorders, vasculitis or a significant bleeding episode from the
             GI tract.

          5. History of severe hypersensitivity reactions to antibodies.

          6. Systemic steroid therapy.

          7. History or autoimmune disease that has required systemic treatment with
             disease-modifying agents, corticosteroids, or immunosuppressive drugs.

          8. Prior organ transplantation including allogenic or autologous stem cell
             transplantation

          9. Prior treatment with anti-CD47 or anti-SIRPα therapy.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase I: Characterize the safety of escalating dose levels of TTI-621 in combination with doxorubicin: type of adverse events
Time Frame:Through completion of Phase I, up to 6 months
Safety Issue:
Description:Characterize the overall safety profile as assessed by the type of adverse events.

Secondary Outcome Measures

Measure:Phase II: Characterize antitumor activity of TTI-621: progression-free survival
Time Frame:Through completion of Phase II, months 6 to 32
Safety Issue:
Description:Characterize progression-free survival (PFS) as defined by RECIST v1.1 criteria.
Measure:Phase II: Characterize antitumor activity of TTI-621: overall survival
Time Frame:Through completion of Phase II, months 6 to 32
Safety Issue:
Description:Characterize overall survival (OS), as defined by RECIST v1.1 criteria.
Measure:Phase II: Characterize antitumor activity of TTI-621: disease control rate
Time Frame:Through completion of Phase II, months 6 to 32
Safety Issue:
Description:Characterize disease control rate (DCR [CR + PR + SD]) as defined by RECIST v1.1 criteria.
Measure:Phase II: Characterize antitumor activity of TTI-621: duration of response
Time Frame:Through completion of Phase II, months 6 to 32
Safety Issue:
Description:Characterize duration of response (DOR) as defined by RECIST v1.1 criteria.
Measure:Phase II: Characterize antitumor activity of TTI-621: time to progression
Time Frame:Through completion of Phase II, months 6 to 32
Safety Issue:
Description:Characterize time to progression as defined by RECIST v1.1 criteria.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Trillium Therapeutics Inc.

Trial Keywords

  • TTI-621
  • Leiomyosarcoma
  • Pleomorphic sarcoma
  • Myxofibrosarcoma
  • Liposarcoma
  • Angiosarcoma
  • Epithelioid sarcoma
  • Doxorubicin
  • CD47
  • immune-oncology
  • chemotherapy
  • anti-SIRPα therapy

Last Updated

August 9, 2021