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.
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
Interventions
Drug | Synonyms | Arms |
---|
TTI-621 | | Dose Escalation |
Doxorubicin | | Dose 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
Name | Type | Description | Interventions |
---|
Dose Escalation | Experimental | | |
Dose Expansion Low Dose (Cohort A) | Experimental | | |
Dose Expansion High Dose (Cohort B) | Experimental | | |
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