A Study to Learn About the Study Medicine (Called Ontorpacept or TTI-621) Given Alone and in Combination With Doxorubicin in People With Leiomyosarcoma

NCT ID: NCT04996004

Last Updated: 2024-12-11

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

76 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-06-22

Study Completion Date

2023-12-07

Brief Summary

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The purpose of this study is to learn about the safety and effects of the study medicine (called Ontorpacept or TTI-621) when given alone and when given in combination with doxorubicin for people with leiomyosarcoma. Leiomyosarcoma is a tumor of the smooth muscles.

This study is seeking participants who have:

* leiomyosarcoma that is advanced or has spread to other parts of the body (metastatic)
* not received prior treatment with anthracyclines (a drug commonly used in patients with some kinds of cancer, including leiomyosarcoma)
* not received more than one prior treatment for their leiomyosarcoma During the first 18 weeks of this study, participants will receive doxorubicin by IV infusion (given directly into a vein) at the study clinic every 3 weeks for a total of 6 doses. Participants will also receive Ontorpacept (TTI-621) by IV infusion at the study clinic on the same day as doxorubicin and again one week later for the first 18 weeks.

After the first 18 weeks, participants will stop receiving doxorubicin but will continue receiving Ontorpacept (TTI-621) as IV infusion every 14 days at the study clinic. They will keep receiving Ontorpacept (TTI-621) until their cancer is no longer responding to treatment.

We will examine the experiences of participants receiving Ontorpacept (TTI-621) in combination with doxorubicin in the first 18 weeks and then Ontorpacept (TTI-621) by itself after the doxorubicin is stopped. This will help us determine if the study medicine Ontorpacept (TTI-621) given with doxorubicin and then by itself is safe and effective.

Participants will be involved in the study for approximately one year, depending on how their cancer responds to the study treatment. They will have study visits about 12 times in the first 18 weeks (when the study medicine Ontorpacept is given with doxorubicin) and then every two weeks after the doxorubicin is stopped and the study medicine Ontorpacept (TTI-621) is given by itself.

Detailed Description

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This trial will be conducted in 2 phases: Phase I (dose escalation of Ontorpacept in combination with fixed-dose doxorubicin) and Phase II (dose expansion of Ontorpacept in combination with fixed-dose doxorubicin).

Phase I will enroll patients with soft-tissue sarcomas including leiomyosarcoma, undifferentiated pleomorphic sarcoma, myxofibrosarcoma, dedifferentiated liposarcoma, angiosarcoma or epithelioid sarcoma to evaluate escalating doses of Ontorpacept (TTI-621) administered in combination with fixed-dose doxorubicin for up to six cycles followed by Ontorpacept (TTI-621) monotherapy.

Phase II will enroll patients with high-grade leiomyosarcoma and will evaluate two dose levels of Ontorpacept (TTI-621) in combination with fixed-dose doxorubicin for up to six cycles followed by Ontorpacept (TTI-621) monotherapy.

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Conditions

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Leiomyosarcoma

Keywords

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Leiomyosarcoma Pleomorphic sarcoma Myxofibrosarcoma Liposarcoma Angiosarcoma Epithelioid sarcoma

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Dose Escalation (Ontorpacept+doxorubicin)

In the dose escalation portion of the study, participants with specific subsets of soft tissue sarcomas who have not received more than one prior line of therapy and have not received an anthracycline in any setting will be enrolled in three escalating dose cohorts to characterize the safety and tolerability of Ontorpacept (TTI-621) when administered in combination with doxorubicin for up to six cycles and followed by Ontorpacept (TTI-621) monotherapy

Group Type EXPERIMENTAL

Ontorpacept (TTI-621)

Intervention Type DRUG

Ontorpacept (TTI-621) will be administered by intravenous infusion.

Doxorubicin

Intervention Type DRUG

75 mg/m\^2 by intravenous infusion in 21-day cycles for a maximum of six cycles.

Dose Expansion Dose Level A (Cohort A)

Participants with high-grade leiomyosarcoma will receive up to six cycles of Ontorpacept (TTI-621) at a pre-specified dose level (Dose Level A) in combination with fixed-dose doxorubicin followed by Ontorpacept (TTI-621) monotherapy to further characterize safety, tolerability, and clinical activity of the treatment regimen.

Group Type EXPERIMENTAL

Ontorpacept (TTI-621)

Intervention Type DRUG

Ontorpacept (TTI-621) will be administered by intravenous infusion.

Doxorubicin

Intervention Type DRUG

75 mg/m\^2 by intravenous infusion in 21-day cycles for a maximum of six cycles.

Dose Expansion Dose Level B (Cohort B)

Participants with high-grade leiomyosarcoma will receive up to six cycles of Ontorpacept (TTI-621) at a pre-specified dose level (Dose Level B) in combination with fixed-dose doxorubicin followed by Ontorpacept (TTI-621) monotherapy to further characterize safety, tolerability, and clinical activity of the treatment regimen.

Group Type EXPERIMENTAL

Ontorpacept (TTI-621)

Intervention Type DRUG

Ontorpacept (TTI-621) will be administered by intravenous infusion.

Doxorubicin

Intervention Type DRUG

75 mg/m\^2 by intravenous infusion in 21-day cycles for a maximum of six cycles.

Dose Expansion Dose Level C (Cohort C)

Participants with high-grade leiomyosarcoma will receive up to six cycles of Ontorpacept (TTI-621) at a pre-specified dose level (Dose Level C) in combination with fixed-dose doxorubicin followed by Ontorpacept (TTI-621) monotherapy to further characterize safety, tolerability, and clinical activity of the treatment regimen.

Group Type EXPERIMENTAL

Ontorpacept (TTI-621)

Intervention Type DRUG

Ontorpacept (TTI-621) will be administered by intravenous infusion.

Doxorubicin

Intervention Type DRUG

75 mg/m\^2 by intravenous infusion in 21-day cycles for a maximum of six cycles.

Interventions

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Ontorpacept (TTI-621)

Ontorpacept (TTI-621) will be administered by intravenous infusion.

Intervention Type DRUG

Doxorubicin

75 mg/m\^2 by intravenous infusion in 21-day cycles for a maximum of six cycles.

Intervention Type DRUG

Other Intervention Names

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Ontorpacept / SIRPα-IgG1 Fc Adriamycin

Eligibility Criteria

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Inclusion Criteria

1. Eastern Co-operative Oncology Group Performance Status Performance Status (ECOG-PS) 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 Response Evaluation Criteria in Solid Tumors (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 (National Cancer Institute Common Terminology Criteria for Adverse Events) 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.

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 (central nervous system) metastases or carcinomatous meningitis.
4. Significant bleeding disorders, vasculitis or a significant bleeding episode from the GI (gastrointestinal) 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 (Cluster of Differentiation 47) or anti-signal regulatory protein alpha (SIRPα) therapy.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Pfizer

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Pfizer CT.gov Call Center

Role: STUDY_DIRECTOR

Pfizer

Locations

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Sarcoma Oncology Research Center

Santa Monica, California, United States

Site Status

Mayo Clinic Florida

Jacksonville, Florida, United States

Site Status

Moffitt Cancer Center

Tampa, Florida, United States

Site Status

University of Iowa Hospital and Clinics

Iowa City, Iowa, United States

Site Status

University of Michigan

Ann Arbor, Michigan, United States

Site Status

MSK Basking Ridge.

Basking Ridge, New Jersey, United States

Site Status

Hackensack University Medical Center

Hackensack, New Jersey, United States

Site Status

MSK Monmouth

Middletown, New Jersey, United States

Site Status

MSK Bergen

Montvale, New Jersey, United States

Site Status

MSK Commack.

Commack, New York, United States

Site Status

MSK Westchester

Harrison, New York, United States

Site Status

Memorial Sloan Kettering Cancer Center - Investigational Drug Service Pharmacy

Long Island City, New York, United States

Site Status

Memorial Sloan Kettering Cancer Center 53rd street.

New York, New York, United States

Site Status

Memorial Sloan Kettering Cancer Center - Main Campus

New York, New York, United States

Site Status

Memorial Sloan Kettering Cancer Center 53rd street.

New York, New York, United States

Site Status

MSK Nassau

Uniondale, New York, United States

Site Status

University Hospitals Cleveland Medical Center

Cleveland, Ohio, United States

Site Status

Oregon Health & Science University (OHSU)

Portland, Oregon, United States

Site Status

Oregon Health and Science University - Center for Health and Healing 1 (CHH1)

Portland, Oregon, United States

Site Status

Oregon Health and Science University - Center for Health and Healing 2(CHH2)

Portland, Oregon, United States

Site Status

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, United States

Site Status

Virginia Cancer Specialists

Fairfax, Virginia, United States

Site Status

University of Wisconsin Clinical Science Center

Madison, Wisconsin, United States

Site Status

Countries

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United States

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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https://pmiform.com/clinical-trial-info-request?StudyID=TTI-621-03

To obtain contact information for a study center near you, click here.

Other Identifiers

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C4961003

Identifier Type: OTHER

Identifier Source: secondary_id

TTI-621-03

Identifier Type: -

Identifier Source: org_study_id