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A Study to Learn About the Study Medicine (Called Ontorpacept or TTI-621) Given Alone and in Combination With Doxorubicin in People With Leiomyosarcoma (TTI-621-03)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04996004
Recruitment Status : Recruiting
First Posted : August 9, 2021
Last Update Posted : May 19, 2023
Sponsor:
Information provided by (Responsible Party):
Pfizer

Brief Summary:

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.


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

Detailed Description:

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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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 22, 2021
Estimated Primary Completion Date : February 5, 2024
Estimated Study Completion Date : February 5, 2024


Arm Intervention/treatment
Experimental: 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
Drug: Ontorpacept (TTI-621)
Ontorpacept (TTI-621) will be administered by intravenous infusion.
Other Name: Ontorpacept / SIRPα-IgG1 Fc

Drug: Doxorubicin
75 mg/m^2 by intravenous infusion in 21-day cycles for a maximum of six cycles.
Other Name: Adriamycin

Experimental: 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.
Drug: Ontorpacept (TTI-621)
Ontorpacept (TTI-621) will be administered by intravenous infusion.
Other Name: Ontorpacept / SIRPα-IgG1 Fc

Drug: Doxorubicin
75 mg/m^2 by intravenous infusion in 21-day cycles for a maximum of six cycles.
Other Name: Adriamycin

Experimental: 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.
Drug: Ontorpacept (TTI-621)
Ontorpacept (TTI-621) will be administered by intravenous infusion.
Other Name: Ontorpacept / SIRPα-IgG1 Fc

Drug: Doxorubicin
75 mg/m^2 by intravenous infusion in 21-day cycles for a maximum of six cycles.
Other Name: Adriamycin




Primary Outcome Measures :
  1. Number of participants by type of adverse events (AEs) by dose level [ Time Frame: Baseline up to 30 days after last administration of TTI-621 or doxorubicin ]
    Among patients enrolled into each dose cohort in the Phase I dose escalation portion of the study, characterize the overall safety profile as assessed by type of adverse events

  2. Number of participants by frequency of adverse events (AEs) by dose level [ Time Frame: Baseline up to 30 days after last administration of TTI-621 or doxorubicin ]
    Among patients enrolled into each dose cohort in the Phase I dose escalation portion of the study, characterize the overall safety profile as assessed by frequency of adverse events

  3. Number of participants by severity of adverse events (AEs) by dose level [ Time Frame: Baseline up to 30 days after last administration of TTI-621 or doxorubicin ]
    Among patients enrolled into each dose cohort in the Phase I dose escalation portion of the study, characterize the overall safety profile as assessed by severity of adverse events

  4. Number of participants by timing of adverse events (AEs) by dose level [ Time Frame: Baseline up to 30 days after last administration of TTI-621 or doxorubicin ]
    Among patients enrolled into each dose cohort in the Phase I dose escalation portion of the study, characterize the overall safety profile as assessed by timing of adverse events

  5. Number of participants by causality of adverse events (AEs) by dose level [ Time Frame: Baseline up to 30 days after last administration of TTI-621 or doxorubicin ]
    Among patients enrolled into each dose cohort in the Phase I dose escalation portion of the study, characterize the overall safety profile as assessed by causality of adverse events

  6. Number of participants with abnormal laboratory results [ Time Frame: Baseline up to 30 days after the last administration of TTI-621 or doxorubicin ]
    Among participants enrolled into each dose cohort in the Phase I dose escalation portion of the study, characterize the overall safety profile as assessed by abnormal laboratory results

  7. Number of participants with abnormal vital signs [ Time Frame: Baseline up to 30 days after the last administration of TTI-621 or doxorubicin ]
    Among participants enrolled into each dose cohort in the Phase I dose escalation portion of the study, characterize the overall safety profile as assessed by abnormal vital signs results

  8. Number of participants with abnormal ECGs (electrocardiograms) [ Time Frame: Baseline up to 30 days after the last administration of TTI-621 or doxorubicin ]
    Among participants enrolled into each dose cohort in the Phase I dose escalation portion of the study, characterize the overall safety profile as assessed by abnormal ECG results

  9. Number of participants with treatment delays or discontinuations [ Time Frame: Baseline up to 30 days after the last administration of TTI-621 or doxorubicin ]
    Among participants enrolled into each dose cohort in the Phase I dose escalation portion of the study, characterize the overall safety profile as assessed by treatment delays or discontinuations

  10. Percentage of patients with objective response [ Time Frame: From initiation of treatment through Month 32 ]
    Evaluate the percentage of patients with objective response (complete response [CR] + partial response [PR]) as defined by RECIST [Response Evaluation Criteria in Solid Tumors] v 1.1 criteria with respect to TTI-621 dose level


Secondary Outcome Measures :
  1. Phase II: Number of participants by type of adverse events (AEs) by dose level [ Time Frame: Baseline up to 30 days after last administration of TTI-621 or doxorubicin ]
    Among patients enrolled into each dose cohort in the Phase II dose expansion portion of the study, characterize the overall safety profile as assessed by type of adverse events

  2. Phase II: Number of participants by frequency of adverse events (AEs) by dose level [ Time Frame: Baseline up to 30 days after last administration of TTI-621 or doxorubicin ]
    Among patients enrolled into each dose cohort in the Phase II dose expansion portion of the study, characterize the overall safety profile as assessed by frequency of adverse events

  3. Phase II: Number of participants by severity of adverse events (AEs) by dose level [ Time Frame: Baseline up to 30 days after last administration of TTI-621 or doxorubicin ]
    Among patients enrolled into each dose cohort in the Phase II dose expansion portion of the study, characterize the overall safety profile as assessed by severity of adverse events

  4. Phase II: Number of participants by timing of adverse events (AEs) by dose level [ Time Frame: Baseline up to 30 days after last administration of TTI-621 or doxorubicin ]
    Among patients enrolled into each dose cohort in the Phase II dose expansion portion of the study, characterize the overall safety profile as assessed by timing of adverse events

  5. Phase II: Number of participants by causality of adverse events (AEs) by dose level [ Time Frame: Baseline up to 30 days after last administration of TTI-621 or doxorubicin ]
    Among patients enrolled into each dose cohort in the Phase II dose expansion portion of the study, characterize the overall safety profile as assessed by causality of adverse events

  6. Phase II: Number of participants with abnormal laboratory results [ Time Frame: Baseline up to 30 days after the last administration of TTI-621 or doxorubicin ]
    Among participants enrolled into each dose cohort in the Phase II dose expansion portion of the study, characterize the overall safety profile as assessed by abnormal laboratory results

  7. Phase II: Number of participants with abnormal vital signs [ Time Frame: Baseline up to 30 days after the last administration of TTI-621 or doxorubicin ]
    Among participants enrolled into each dose cohort in the Phase II dose expansion portion of the study, characterize the overall safety profile as assessed by abnormal vital signs results

  8. Phase II: Number of participants with abnormal ECGs (electrocardiograms) [ Time Frame: Baseline up to 30 days after the last administration of TTI-621 or doxorubicin ]
    Among participants enrolled into each dose cohort in the Phase II dose expansion portion of the study, characterize the overall safety profile as assessed by abnormal ECG results

  9. Phase II: Number of participants with treatment delays or discontinuations [ Time Frame: Baseline up to 30 days after the last administration of TTI-621 or doxorubicin ]
    Among participants enrolled into each dose cohort in the Phase II dose expansion portion of the study, characterize the overall safety profile as assessed by treatment delays or discontinuations

  10. Phase II: Progression-free survival (PFS) [ Time Frame: From initiation of treatment through Month 32 ]
    Among patients enrolled into each dose cohort in the Phase II dose expansion portion of the study, characterize progression-free survival (PFS) as defined by RECIST v1.1 criteria.

  11. Phase II: Overall survival [ Time Frame: From initiation of treatment until death ]
    Among patients enrolled into each dose cohort in the Phase II dose expansion portion of the study, characterize overall survival (OS)

  12. Phase II: Disease control rate (DCR) [ Time Frame: From initiation of treatment through Month 32 ]
    Among patients enrolled into each dose cohort in the Phase II dose expansion portion of the study, characterize disease control rate (DCR [CR + PR + SD (stable disease)]) as defined by RECIST v1.1 criteria.

  13. Phase II: Duration of response [ Time Frame: From initiation of treatment through Month 32 ]
    Among patients enrolled into each dose cohort in the Phase II dose expansion portion of the study, characterize duration of response (DOR) as defined by RECIST v1.1 criteria.

  14. Phase II: Time to disease progression [ Time Frame: From initiation of treatment through Month 32 ]
    Among patients enrolled into each dose cohort in the Phase II dose expansion portion of the study, characterize time to progression as defined by RECIST v1.1 criteria.

  15. Phase II: Duration of disease control [ Time Frame: From initiation of treatment through Month 32 ]
    Among patients enrolled into each dose cohort in the Phase II dose expansion portion of the study, characterize characterize duration of response (DOR) as defined by RECIST v1.1 criteria.

  16. Phase II: Time to development of new metastases [ Time Frame: From initiation of treatment through Month 32 ]
    Among patients enrolled into each dose cohort in the Phase II dose expansion portion of the study, characterize the time to develop of new metastatic lesions as defined by RECIST v1.1 criteria

  17. Phase II: Change in ECOG (Eastern Cooperative Oncology Group) Performance status [ Time Frame: From initiation of treatment through Month 32 ]
    Among patients enrolled into each dose cohort in the Phase II dose expansion portion of the study, characterize the change in performance status using the ECOG performance status scale

  18. Phase II: Change from baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (EORTC QLQ-C30) [ Time Frame: From initiation of treatment through Month 32 ]
    Among patients enrolled into each dose cohort in the Phase II dose expansion portion of the study, characterize the change of patient-reported outcomes (PRO) using the EORTC QLQ-C30 questionnaire. Scale is 0 to 100. Higher score for the functioning scales and global health status denote a better level of functioning (i.e. a better state of the patient), while higher scores on the symptom and single-item scales indicate a higher level of symptoms (i.e. a worse state of the patient)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
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 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.

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 (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.

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
Layout table for location contacts
Contact: Pfizer CT.gov Pfizer CT.gov Call Center 1-800-718-1021 ClinicalTrials.gov_Inquiries@pfizer.com

Locations
Show Show 21 study locations
Sponsors and Collaborators
Pfizer
Investigators
Layout table for investigator information
Study Director: Pfizer CT.gov Call Center Pfizer
Additional Information:
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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT04996004    
Other Study ID Numbers: TTI-621-03
C4961003 ( Other Identifier: Alias Study Number )
First Posted: August 9, 2021    Key Record Dates
Last Update Posted: May 19, 2023
Last Verified: May 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

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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 Pfizer:
Leiomyosarcoma
Pleomorphic sarcoma
Myxofibrosarcoma
Liposarcoma
Angiosarcoma
Epithelioid sarcoma
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