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

Sponsor
Pfizer (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04996004
Collaborator
(none)
80
Enrollment
27
Locations
3
Arms
30.4
Anticipated Duration (Months)
3
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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
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.

Study Design

Study Type:
Interventional
Anticipated 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 :
Jun 22, 2021
Anticipated Primary Completion Date :
Nov 3, 2023
Anticipated Study Completion Date :
Jan 4, 2024

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

  1. Phase I: Characterize the safety of escalating dose levels of TTI-621 in combination with doxorubicin: type of adverse events [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [Through completion of Phase II, months 6 to 32]

    Characterize time to progression as defined by RECIST v1.1 criteria.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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.

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

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

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

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

  7. Adequate organ and hematologic function.

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

  9. Anthracycline-naïve.

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

  11. 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.

  12. 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.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Cancer Center of Southern California Santa Monica California United States 90403
2 Sarcoma Oncology Research Center Santa Monica California United States 90403
3 Cancer Center Referral Office Jacksonville Florida United States 32224
4 Moffitt Cancer Center Tampa Florida United States 33612
5 University of Iowa Hospitals and Clinics Iowa City Iowa United States 52242
6 University of Michigan Rogel Cancer Center Ann Arbor Michigan United States 48109
7 MSK Basking Ridge. Basking Ridge New Jersey United States 07920
8 MSK Monmouth Middletown New Jersey United States 07748
9 MSK Bergen Montvale New Jersey United States 07645
10 MSK Commack. Commack New York United States 11725
11 MSK Westchester Harrison New York United States 10604
12 Memorial Sloan Kettering Cancer Center - Investigational Drug Service Pharmacy Long Island City New York United States 11101
13 Memorial Sloan Kettering Cancer Center - Main Campus New York New York United States 10065
14 Memorial Sloan Kettering Cancer Center - Main Campus New York New York United States 10065
15 Memorial Sloan Kettering Cancer Center 53rd street. New York New York United States 10065
16 MSK Nassau Uniondale New York United States 11553
17 Duke Sarcoma Research Durham North Carolina United States 27710
18 University Hospitals Seidman Cancer Center Cleveland Ohio United States 44106
19 Oregon Health & Science University (OHSU) Portland Oregon United States 97239
20 Oregon Health & Science University Portland Oregon United States 97239
21 Oregon Health and Science University - Center for Health and Healing 1(CHHI) Portland Oregon United States 97239
22 Oregon Health and Science University - Center for Health and Healing 2(CHH2) Portland Oregon United States 97239
23 UPMC Cancer Center Pavilion Pittsburgh Pennsylvania United States 15232
24 Virginia Cancer Specialists Fairfax Virginia United States 22031
25 Virginia Cancer Specialists Fairfax Virginia United States 22031
26 University of Wisconsin Madison Wisconsin United States 53715
27 University of Wisconsin Clinical Science Center Madison Wisconsin United States 53792

Sponsors and Collaborators

  • Pfizer

Investigators

  • Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

None provided.
Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT04996004
Other Study ID Numbers:
  • TTI-621-03
  • C4961003
First Posted:
Aug 9, 2021
Last Update Posted:
Jul 28, 2022
Last Verified:
Jul 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Pfizer
TTI-621
Leiomyosarcoma
Pleomorphic sarcoma
Myxofibrosarcoma
Liposarcoma
Angiosarcoma
Epithelioid sarcoma
Doxorubicin
CD47
immune-oncology
chemotherapy
anti-SIRPα therapy
Additional relevant MeSH terms:
Leiomyosarcoma
Doxorubicin

Study Results

No Results Posted as of Jul 28, 2022