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

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ClinicalTrials.gov Identifier: NCT04996004
Recruitment Status : Recruiting
First Posted : August 9, 2021
Last Update Posted : August 9, 2021
Sponsor:
Information provided by (Responsible Party):
Trillium Therapeutics Inc.

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

Condition or disease Intervention/treatment Phase
Leiomyosarcoma Drug: TTI-621 Drug: Doxorubicin Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/II Study of TTI-621 in Combination With Doxorubicin in Patients With Unresectable or Metastatic High-Grade Leiomyosarcoma
Actual Study Start Date : June 25, 2021
Estimated Primary Completion Date : June 30, 2023
Estimated Study Completion Date : July 31, 2024


Arm Intervention/treatment
Experimental: Dose Escalation Drug: TTI-621
TTI-621 will be administered by intravenous infusion.

Drug: Doxorubicin
75 mg/m^2 by intravenous infusion on Day 1 of each 21-day cycle for a maximum of 6 cycles.

Experimental: Dose Expansion Low Dose (Cohort A) Drug: TTI-621
TTI-621 will be administered by intravenous infusion.

Drug: Doxorubicin
75 mg/m^2 by intravenous infusion on Day 1 of each 21-day cycle for a maximum of 6 cycles.

Experimental: Dose Expansion High Dose (Cohort B) Drug: TTI-621
TTI-621 will be administered by intravenous infusion.

Drug: Doxorubicin
75 mg/m^2 by intravenous infusion on Day 1 of each 21-day cycle for a maximum of 6 cycles.




Primary Outcome Measures :
  1. 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 ]
    Characterize the overall safety profile as assessed by the type of adverse events.

  2. Phase I: Characterize the safety of escalating dose levels of TTI-621 in combination with doxorubicin: frequency of adverse events [ Time Frame: Through completion of Phase I, up to 6 months ]
    Characterize the overall safety profile as assessed by the frequency of adverse events.

  3. Phase I: Characterize the safety of escalating dose levels of TTI-621 in combination with doxorubicin: severity of adverse events [ Time Frame: Through completion of Phase I, up to 6 months ]
    Characterize the overall safety profile as assessed by the severity of adverse events.

  4. Phase I: Characterize the safety of escalating dose levels of TTI-621 in combination with doxorubicin: timing of adverse events [ Time Frame: Through completion of Phase I, up to 6 months ]
    Characterize the overall safety profile as assessed by the timing of adverse events.

  5. Phase I: Characterize the safety of escalating dose levels of TTI-621 in combination with doxorubicin: causal relationship of adverse events [ Time Frame: Through completion of Phase I, up to 6 months ]
    Characterize the overall safety profile as assessed by the causal relationship of adverse events.

  6. Phase II: Characterize the safety of selected dose levels of TTI-621 in combination with doxorubicin: frequency of adverse events [ Time Frame: Through completion of Phase II, months 6 to 32 ]
    Characterize the overall safety profile as assessed by the frequency of adverse events.

  7. Phase II: Characterize the safety of selected dose levels of TTI-621 in combination with doxorubicin: severity of adverse events [ Time Frame: Through completion of Phase II, months 6 to 32 ]
    Characterize the overall safety profile as assessed by the severity of any adverse events.

  8. Phase II: Characterize the safety of selected dose levels of TTI-621 in combination with doxorubicin: timing of adverse events [ Time Frame: Through completion of Phase II, months 6 to 32 ]
    Characterize the overall safety profile as assessed by the timing of any adverse events.

  9. Phase II: Characterize the safety of selected dose levels of TTI-621 in combination with doxorubicin: causal relationship of adverse events [ Time Frame: Through completion of Phase II, months 6 to 32 ]
    Characterize the overall safety profile as assessed by the causal relationship of any adverse events.

  10. Phase II: Percentage of Patients with Objective Response [ Time Frame: Through completion of Phase II, months 6 to 32 ]
    Evaluation the percentage of patients with objective response (complete response [CR] + partial response [PR]) as defined by RECIST v 1.1 criteria.


Secondary Outcome Measures :
  1. Phase II: Characterize antitumor activity of TTI-621: progression-free survival [ Time Frame: Through completion of Phase II, months 6 to 32 ]
    Characterize progression-free survival (PFS) as defined by RECIST v1.1 criteria.

  2. Phase II: Characterize antitumor activity of TTI-621: overall survival [ Time Frame: Through completion of Phase II, months 6 to 32 ]
    Characterize overall survival (OS), as defined by RECIST v1.1 criteria.

  3. Phase II: Characterize antitumor activity of TTI-621: disease control rate [ Time Frame: Through completion of Phase II, months 6 to 32 ]
    Characterize disease control rate (DCR [CR + PR + SD]) as defined by RECIST v1.1 criteria.

  4. Phase II: Characterize antitumor activity of TTI-621: duration of response [ Time Frame: Through completion of Phase II, months 6 to 32 ]
    Characterize duration of response (DOR) as defined by RECIST v1.1 criteria.

  5. Phase II: Characterize antitumor activity of TTI-621: time to progression [ Time Frame: Through completion of Phase II, months 6 to 32 ]
    Characterize time to progression as defined by RECIST v1.1 criteria.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04996004


Contacts
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Contact: Karen Makhuli 857 412-7029 Clinicalinfo@TrilliumTherapeutics.com

Locations
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United States, California
Cancer Center of Southern California Recruiting
Santa Monica, California, United States, 90403
Contact: Victoria S Chua-Alcala    310-552-9999    vchua@sarcomaoncology.com   
Sponsors and Collaborators
Trillium Therapeutics Inc.
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Responsible Party: Trillium Therapeutics Inc.
ClinicalTrials.gov Identifier: NCT04996004    
Other Study ID Numbers: TTI-621-03
First Posted: August 9, 2021    Key Record Dates
Last Update Posted: August 9, 2021
Last Verified: August 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Trillium Therapeutics Inc.:
TTI-621
Leiomyosarcoma
Pleomorphic sarcoma
Myxofibrosarcoma
Liposarcoma
Angiosarcoma
Epithelioid sarcoma
Doxorubicin
CD47
immune-oncology
chemotherapy
anti-SIRPα therapy
Additional relevant MeSH terms:
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Leiomyosarcoma
Neoplasms, Muscle Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Sarcoma
Doxorubicin
Antibiotics, Antineoplastic
Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action