Back to resultsA 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)
Primary Purpose
Leiomyosarcoma
Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Ontorpacept (TTI-621)
Doxorubicin
Sponsored by
About this trial
This is an interventional treatment trial for Leiomyosarcoma focused on measuring Leiomyosarcoma, Pleomorphic sarcoma, Myxofibrosarcoma, Liposarcoma, Angiosarcoma, Epithelioid sarcoma
Eligibility Criteria
Key Inclusion Criteria:
- Eastern Co-operative Oncology Group Performance Status Performance Status (ECOG-PS) 0 or 1.
Histologically-confirmed high-grade soft tissue sarcoma that is metastatic or locally advanced and not amenable to curative treatment with surgery or radiation.
- In the Dose Escalation phase, indications will be limited to high-grade leiomyosarcoma, undifferentiated pleomorphic sarcoma, myxofibrosarcoma, dedifferentiated liposarcoma, angiosarcoma and epithelioid sarcoma
- In the Dose Expansion phase, indications will be limited to high-grade leiomyosarcoma.
- Objective evidence of disease progression unless disease is newly-diagnosed.
- Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (expansion cohorts).
- Adequate organ and hematologic function.
- No more than 1 prior treatment regimen for advanced disease, which is limited to gemcitabine with docetaxel.
- Anthracycline-naïve.
- Patients who were treated with a prior chemotherapy regimen must have completed treatment at least three weeks before initiation of study treatment.
- 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.
- 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:
- History of acute coronary syndromes.
- History of or current Class II, III, or IV heart failure.
- History or evidence of known CNS (central nervous system) metastases or carcinomatous meningitis.
- Significant bleeding disorders, vasculitis or a significant bleeding episode from the GI (gastrointestinal) tract.
- History of severe hypersensitivity reactions to antibodies.
- Systemic steroid therapy.
- History or autoimmune disease that has required systemic treatment with disease-modifying agents, corticosteroids, or immunosuppressive drugs.
- Prior organ transplantation including allogenic or autologous stem cell transplantation
- Prior treatment with anti-CD47 (Cluster of Differentiation 47) or anti-signal regulatory protein alpha (SIRPα) therapy.
Sites / Locations
- Sarcoma Oncology Research Center
- Mayo Clinic Florida
- Moffitt Cancer Center
- University of Iowa Hospital and Clinics
- University of Michigan
- MSK Basking Ridge.
- MSK Monmouth
- MSK Bergen
- MSK Commack.
- MSK Westchester
- Memorial Sloan Kettering Cancer Center - Investigational Drug Service Pharmacy
- Memorial Sloan Kettering Cancer Center - Main Campus
- Memorial Sloan Kettering Cancer Center 53rd street.
- MSK Nassau
- University Hospitals Cleveland Medical Center
- Oregon Health & Science University (OHSU)
- Oregon Health and Science University - Center for Health and Healing 1(CHHI)
- Oregon Health and Science University - Center for Health and Healing 2(CHH2)
- UPMC Hillman Cancer Center
- Virginia Cancer Specialists
- University of Wisconsin Clinical Science Center
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
Dose Escalation (Ontorpacept+doxorubicin)
Dose Expansion Dose Level A (Cohort A)
Dose Expansion Dose Level B (Cohort B)
Dose Expansion Dose Level C (Cohort C)
Arm Description
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
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.
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.
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.
Outcomes
Primary Outcome Measures
Number of Participants with Treatment Emergent Adverse Events (TEAE) and Serious Adverse Events (SAE)
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship with the study treatment.
TEAE was defined as an AE with onset date occurring during the on-treatment period.
SAE was defined as one of the following: was fatal or life-threatening; resulted in persistent or significant disability/incapacity; constituted a congenital anomaly/birth defect; was medically significant; required inpatient hospitalization or prolongation of existing hospitalization.
AEs included all SAEs and non-SAEs.
Among patients in the dose escalation portion of the study.
Mean and changes from baseline in blood pressure
Mean and changes from baseline in blood pressure will be summarized with continuous descriptive statistics.
Among patients in the dose escalation portion of the study.
Categorical summary of ECG parameters
Number of participants with notable ECG values will be summarized.
Among patients in the dose escalation portion of the study.
Number of participants with abnormal laboratory results
The number of participants with following laboratory abnormalities meeting any of the Grades 1 to 4 classified according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) toxicity grading version 5.0.
Among patients in the dose escalation portion of the study.
Number of participants with dose modifications
The number of drug administrations with dose reduction, infusion held or permanently withdrawn.
Among patients in the dose escalation portion of the study.
Percentage of patients with objective response
The percentage of patients with confirmed objective response (complete response [CR] + partial response [PR]) as defined by RECIST [Response Evaluation Criteria in Solid Tumors] v 1.1 criteria.
Confirmed responses are those that persist on repeat imaging study ≥4 weeks after initial documentation of response.
Patients in the dose escalation and dose expansion of the study.
Mean and changes from baseline in weight
Mean and changes from baseline in weight will be summarized with continuous descriptive statistics.
Among patients in the dose escalation portion of the study.
Secondary Outcome Measures
Number of Participants with Treatment Emergent Adverse Events (TEAE) and Serious Adverse Events (SAE)
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship with the study treatment.
TEAE was defined as an AE with onset date occurring during the on-treatment period.
SAE was defined as one of the following: was fatal or life-threatening; resulted in persistent or significant disability/incapacity; constituted a congenital anomaly/birth defect; was medically significant; required inpatient hospitalization or prolongation of existing hospitalization.
AEs included all SAEs and non-SAEs.
Among patients in the dose expansion portion of the study.
Mean and Changes from baseline in blood pressure
Mean and changes from baseline in blood pressure will be summarized with continuous descriptive statistics.
Among patients in the dose expansion portion of the study.
Categorical summary of ECG parameters
Number of participants with notable ECG values will be summarized.
Among patients in the dose expansion portion of the study.
Number of participants with abnormal laboratory results
The number of participants with following laboratory abnormalities meeting any of the Grades 1 to 4 classified according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) toxicity grading version 5.0.
Among patients in the dose expansion portion of the study.
Number of participants with dose modifications
The number of drug administrations with dose reduction, infusion held or permanently withdrawn.
Among patients in the dose expansion portion of the study.
Progression-free survival (PFS)
PFS is defined as time from the first dose of study treatment to the first documentation of objective tumor progression or to death due to any cause, whichever occurs first. Median PFS with 95% CI will be summarized using the Kaplan-Meier method.
Patients in the dose escalation and dose expansion of the study.
Overall Survival (OS)
OS is defined as time from the first dose of study treatment to death due to any cause. Median OS with 95% CI will be summarized using the Kaplan-Meier method.
Patients in the dose escalation and dose expansion of the study.
Disease control rate (DCR)
DCR is defined as the percent of participants with a confirmed complete response (CR), confirmed partial response (PR) or stable disease (SD).
Patients in the dose escalation and dose expansion of the study.
Duration of response (DOR)
DOR is defined for participants with an OR per RECIST version 1.1, as the time from the first documentation of objective tumor response to the first documentation of objective tumor progression or death due to any cause, whichever occurs first. Median DOR with 95% CI will be summarized using the Kaplan-Meier method.
Patients in the dose escalation and dose expansion of the study.
Time to disease progression (TTP)
TTP is defined as time from the first dose of study treatment to the first documentation of objective tumor progression. Median TTP with 95% CI will be summarized using the Kaplan-Meier method.
Patients in the dose escalation and dose expansion of the study.
Duration of disease control (DDC)
DDC is defined as the time from the first dose to the date of documented progression or death of any cause and will be calculated for patients who achieve a CR, PR or SD. Median DDC with 95% CI will be summarized using the Kaplan-Meier method.
Patients in the dose escalation and dose expansion of the study.
Time to new metastatic lesions appearance
Time to new metastases is defined as the time from the first dose to a new metastatic lesion appearance. Patients who progress or die without new metastases will be censored at their date of progression or death. Median time to event with 95% CI will be summarized using the Kaplan-Meier method.
Patients in the dose escalation and dose expansion of the study.
Number of participants with a worsening of ECOG (Eastern Cooperative Oncology Group) status from baseline
ECOG Performance Status will be assessed as described in the protocol Appendix A.
Patients in the dose escalation and dose expansion of the study.
Number of participants with a worsening of European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (EORTC QLQ-C30)
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).
Patients in the dose escalation and dose expansion of the study.
Mean and changes from baseline in weight
Mean and changes from baseline in weight will be summarized with continuous descriptive statistics.
Among patients in the dose escalation portion of the study.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04996004
Brief Title
A Study to Learn About the Study Medicine (Called Ontorpacept or TTI-621) Given Alone and in Combination With Doxorubicin in People With Leiomyosarcoma
Acronym
TTI-621-03
Official Title
A Phase I/II Study of TTI-621 in Combination With Doxorubicin in Patients With Unresectable or Metastatic High-Grade Leiomyosarcoma
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
June 22, 2021 (Actual)
Primary Completion Date
December 24, 2023 (Anticipated)
Study Completion Date
December 24, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pfizer
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
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.
.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leiomyosarcoma
Keywords
Leiomyosarcoma, Pleomorphic sarcoma, Myxofibrosarcoma, Liposarcoma, Angiosarcoma, Epithelioid sarcoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
76 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Dose Escalation (Ontorpacept+doxorubicin)
Arm Type
Experimental
Arm Description
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
Arm Title
Dose Expansion Dose Level A (Cohort A)
Arm Type
Experimental
Arm Description
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.
Arm Title
Dose Expansion Dose Level B (Cohort B)
Arm Type
Experimental
Arm Description
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.
Arm Title
Dose Expansion Dose Level C (Cohort C)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Ontorpacept (TTI-621)
Other Intervention Name(s)
Ontorpacept / SIRPα-IgG1 Fc
Intervention Description
Ontorpacept (TTI-621) will be administered by intravenous infusion.
Intervention Type
Drug
Intervention Name(s)
Doxorubicin
Other Intervention Name(s)
Adriamycin
Intervention Description
75 mg/m^2 by intravenous infusion in 21-day cycles for a maximum of six cycles.
Primary Outcome Measure Information:
Title
Number of Participants with Treatment Emergent Adverse Events (TEAE) and Serious Adverse Events (SAE)
Description
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship with the study treatment.
TEAE was defined as an AE with onset date occurring during the on-treatment period.
SAE was defined as one of the following: was fatal or life-threatening; resulted in persistent or significant disability/incapacity; constituted a congenital anomaly/birth defect; was medically significant; required inpatient hospitalization or prolongation of existing hospitalization.
AEs included all SAEs and non-SAEs.
Among patients in the dose escalation portion of the study.
Time Frame
From the first dose of study treatment through minimum (30 days + last dose of study treatment, start day of new anti-cancer drug therapy - 1 day) (Up to approximately 17 months)
Title
Mean and changes from baseline in blood pressure
Description
Mean and changes from baseline in blood pressure will be summarized with continuous descriptive statistics.
Among patients in the dose escalation portion of the study.
Time Frame
Baseline up to safety FU visit ((Up to approximately 17 months)
Title
Categorical summary of ECG parameters
Description
Number of participants with notable ECG values will be summarized.
Among patients in the dose escalation portion of the study.
Time Frame
Baseline up to safety FU visit (Up to approximately 17 months)
Title
Number of participants with abnormal laboratory results
Description
The number of participants with following laboratory abnormalities meeting any of the Grades 1 to 4 classified according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) toxicity grading version 5.0.
Among patients in the dose escalation portion of the study.
Time Frame
Baseline up to safety FU visit (Up to approximately 17 months)
Title
Number of participants with dose modifications
Description
The number of drug administrations with dose reduction, infusion held or permanently withdrawn.
Among patients in the dose escalation portion of the study.
Time Frame
First dose to last dose (Up to approximately 16 months)
Title
Percentage of patients with objective response
Description
The percentage of patients with confirmed objective response (complete response [CR] + partial response [PR]) as defined by RECIST [Response Evaluation Criteria in Solid Tumors] v 1.1 criteria.
Confirmed responses are those that persist on repeat imaging study ≥4 weeks after initial documentation of response.
Patients in the dose escalation and dose expansion of the study.
Time Frame
Initiation of treatment up to progression or initiation of new anti-cancer therapy or discontinuation from study (Up to approximately 20 months)
Title
Mean and changes from baseline in weight
Description
Mean and changes from baseline in weight will be summarized with continuous descriptive statistics.
Among patients in the dose escalation portion of the study.
Time Frame
Baseline up to safety FU visit (Up to approximately 17 months)
Secondary Outcome Measure Information:
Title
Number of Participants with Treatment Emergent Adverse Events (TEAE) and Serious Adverse Events (SAE)
Description
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship with the study treatment.
TEAE was defined as an AE with onset date occurring during the on-treatment period.
SAE was defined as one of the following: was fatal or life-threatening; resulted in persistent or significant disability/incapacity; constituted a congenital anomaly/birth defect; was medically significant; required inpatient hospitalization or prolongation of existing hospitalization.
AEs included all SAEs and non-SAEs.
Among patients in the dose expansion portion of the study.
Time Frame
From the first dose of study treatment through minimum (30 days + last dose of study treatment, start day of new anti-cancer drug therapy - 1 day) (Up to approximately 20 months)
Title
Mean and Changes from baseline in blood pressure
Description
Mean and changes from baseline in blood pressure will be summarized with continuous descriptive statistics.
Among patients in the dose expansion portion of the study.
Time Frame
Baseline up to safety FU visit (Up to approximately 20 months)
Title
Categorical summary of ECG parameters
Description
Number of participants with notable ECG values will be summarized.
Among patients in the dose expansion portion of the study.
Time Frame
Baseline up to safety FU visit (Up to approximately 20 months)
Title
Number of participants with abnormal laboratory results
Description
The number of participants with following laboratory abnormalities meeting any of the Grades 1 to 4 classified according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) toxicity grading version 5.0.
Among patients in the dose expansion portion of the study.
Time Frame
Baseline up to safety FU visit (Up to approximately 20 months)
Title
Number of participants with dose modifications
Description
The number of drug administrations with dose reduction, infusion held or permanently withdrawn.
Among patients in the dose expansion portion of the study.
Time Frame
First dose to last dose (Up to approximately 20 months)
Title
Progression-free survival (PFS)
Description
PFS is defined as time from the first dose of study treatment to the first documentation of objective tumor progression or to death due to any cause, whichever occurs first. Median PFS with 95% CI will be summarized using the Kaplan-Meier method.
Patients in the dose escalation and dose expansion of the study.
Time Frame
Initiation of treatment up to progression or initiation of new anti-cancer therapy or discontinuation from study (Up to approximately 20 months)
Title
Overall Survival (OS)
Description
OS is defined as time from the first dose of study treatment to death due to any cause. Median OS with 95% CI will be summarized using the Kaplan-Meier method.
Patients in the dose escalation and dose expansion of the study.
Time Frame
From initiation of treatment until discontinuation from study (Up to approximately 29 months)
Title
Disease control rate (DCR)
Description
DCR is defined as the percent of participants with a confirmed complete response (CR), confirmed partial response (PR) or stable disease (SD).
Patients in the dose escalation and dose expansion of the study.
Time Frame
Initiation of treatment up to progression or initiation of new anti-cancer therapy or discontinuation from study (Up to approximately 20 months)
Title
Duration of response (DOR)
Description
DOR is defined for participants with an OR per RECIST version 1.1, as the time from the first documentation of objective tumor response to the first documentation of objective tumor progression or death due to any cause, whichever occurs first. Median DOR with 95% CI will be summarized using the Kaplan-Meier method.
Patients in the dose escalation and dose expansion of the study.
Time Frame
Date of first documentation of an objective response to progression or initiation of new anti-cancer therapy or discontinuation from study (Up to approximately 20 months)
Title
Time to disease progression (TTP)
Description
TTP is defined as time from the first dose of study treatment to the first documentation of objective tumor progression. Median TTP with 95% CI will be summarized using the Kaplan-Meier method.
Patients in the dose escalation and dose expansion of the study.
Time Frame
Initiation of treatment up to progression or initiation of new anti-cancer therapy or discontinuation from study (Up to approximately 20 months)
Title
Duration of disease control (DDC)
Description
DDC is defined as the time from the first dose to the date of documented progression or death of any cause and will be calculated for patients who achieve a CR, PR or SD. Median DDC with 95% CI will be summarized using the Kaplan-Meier method.
Patients in the dose escalation and dose expansion of the study.
Time Frame
Initiation of treatment up to progression or initiation of new anti-cancer therapy or discontinuation from study (Up to approximately 20 months)
Title
Time to new metastatic lesions appearance
Description
Time to new metastases is defined as the time from the first dose to a new metastatic lesion appearance. Patients who progress or die without new metastases will be censored at their date of progression or death. Median time to event with 95% CI will be summarized using the Kaplan-Meier method.
Patients in the dose escalation and dose expansion of the study.
Time Frame
Initiation of treatment up to progression or initiation of new anti-cancer therapy or discontinuation from study (Up to approximately 20 months)
Title
Number of participants with a worsening of ECOG (Eastern Cooperative Oncology Group) status from baseline
Description
ECOG Performance Status will be assessed as described in the protocol Appendix A.
Patients in the dose escalation and dose expansion of the study.
Time Frame
Baseline up to safety FU visit (Up to approximately 20 months)
Title
Number of participants with a worsening of European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (EORTC QLQ-C30)
Description
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).
Patients in the dose escalation and dose expansion of the study.
Time Frame
Baseline up to safety FU visit (Up to approximately 20 months)
Title
Mean and changes from baseline in weight
Description
Mean and changes from baseline in weight will be summarized with continuous descriptive statistics.
Among patients in the dose escalation portion of the study.
Time Frame
Baseline up to safety FU visit (Up to approximately 20 months)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria:
Eastern Co-operative Oncology Group Performance Status Performance Status (ECOG-PS) 0 or 1.
Histologically-confirmed high-grade soft tissue sarcoma that is metastatic or locally advanced and not amenable to curative treatment with surgery or radiation.
In the Dose Escalation phase, indications will be limited to high-grade leiomyosarcoma, undifferentiated pleomorphic sarcoma, myxofibrosarcoma, dedifferentiated liposarcoma, angiosarcoma and epithelioid sarcoma
In the Dose Expansion phase, indications will be limited to high-grade leiomyosarcoma.
Objective evidence of disease progression unless disease is newly-diagnosed.
Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (expansion cohorts).
Adequate organ and hematologic function.
No more than 1 prior treatment regimen for advanced disease, which is limited to gemcitabine with docetaxel.
Anthracycline-naïve.
Patients who were treated with a prior chemotherapy regimen must have completed treatment at least three weeks before initiation of study treatment.
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.
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:
History of acute coronary syndromes.
History of or current Class II, III, or IV heart failure.
History or evidence of known CNS (central nervous system) metastases or carcinomatous meningitis.
Significant bleeding disorders, vasculitis or a significant bleeding episode from the GI (gastrointestinal) tract.
History of severe hypersensitivity reactions to antibodies.
Systemic steroid therapy.
History or autoimmune disease that has required systemic treatment with disease-modifying agents, corticosteroids, or immunosuppressive drugs.
Prior organ transplantation including allogenic or autologous stem cell transplantation
Prior treatment with anti-CD47 (Cluster of Differentiation 47) or anti-signal regulatory protein alpha (SIRPα) therapy.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pfizer CT.gov Call Center
Organizational Affiliation
Pfizer
Official's Role
Study Director
Facility Information:
Facility Name
Sarcoma Oncology Research Center
City
Santa Monica
State/Province
California
ZIP/Postal Code
90403
Country
United States
Facility Name
Mayo Clinic Florida
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32224
Country
United States
Facility Name
Moffitt Cancer Center
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
University of Iowa Hospital and Clinics
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
MSK Basking Ridge.
City
Basking Ridge
State/Province
New Jersey
ZIP/Postal Code
07920
Country
United States
Facility Name
MSK Monmouth
City
Middletown
State/Province
New Jersey
ZIP/Postal Code
07748
Country
United States
Facility Name
MSK Bergen
City
Montvale
State/Province
New Jersey
ZIP/Postal Code
07645
Country
United States
Facility Name
MSK Commack.
City
Commack
State/Province
New York
ZIP/Postal Code
11725
Country
United States
Facility Name
MSK Westchester
City
Harrison
State/Province
New York
ZIP/Postal Code
10604
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center - Investigational Drug Service Pharmacy
City
Long Island City
State/Province
New York
ZIP/Postal Code
11101
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center - Main Campus
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center 53rd street.
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
MSK Nassau
City
Uniondale
State/Province
New York
ZIP/Postal Code
11553
Country
United States
Facility Name
University Hospitals Cleveland Medical Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
Oregon Health & Science University (OHSU)
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
Oregon Health and Science University - Center for Health and Healing 1(CHHI)
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
Oregon Health and Science University - Center for Health and Healing 2(CHH2)
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
UPMC Hillman Cancer Center
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15232
Country
United States
Facility Name
Virginia Cancer Specialists
City
Fairfax
State/Province
Virginia
ZIP/Postal Code
22031
Country
United States
Facility Name
University of Wisconsin Clinical Science Center
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing 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.
IPD Sharing URL
https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests
Links:
URL
https://pmiform.com/clinical-trial-info-request?StudyID=TTI-621-03
Description
To obtain contact information for a study center near you, click here.
Learn more about this trial
A Study to Learn About the Study Medicine (Called Ontorpacept or TTI-621) Given Alone and in Combination With Doxorubicin in People With Leiomyosarcoma
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