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

Leiomyosarcoma Clinical Trial

— 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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04996004
• Other study ID #: TTI-621-03
• Secondary ID: C4961003
• Status: Terminated
• Phase: Phase 2
• Start date: June 22, 2021
• Est. completion date: December 7, 2023

Study information

• Verified date: April 2024
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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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Recruitment information / eligibility

• Status: Terminated
• Enrollment: 75
• Est. completion date: December 7, 2023
• Est. primary completion date: December 7, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 (SIRPa) therapy.

Related Conditions & MeSH terms

• Leiomyosarcoma

Intervention

Drug:
• Ontorpacept (TTI-621)
Ontorpacept (TTI-621) will be administered by intravenous infusion.
• Doxorubicin
75 mg/m^2 by intravenous infusion in 21-day cycles for a maximum of six cycles.

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan
United States	MSK Basking Ridge.	Basking Ridge	New Jersey
United States	University Hospitals Cleveland Medical Center	Cleveland	Ohio
United States	MSK Commack.	Commack	New York
United States	Virginia Cancer Specialists	Fairfax	Virginia
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	MSK Westchester	Harrison	New York
United States	University of Iowa Hospital and Clinics	Iowa City	Iowa
United States	Mayo Clinic Florida	Jacksonville	Florida
United States	Memorial Sloan Kettering Cancer Center - Investigational Drug Service Pharmacy	Long Island City	New York
United States	University of Wisconsin Clinical Science Center	Madison	Wisconsin
United States	MSK Monmouth	Middletown	New Jersey
United States	MSK Bergen	Montvale	New Jersey
United States	Memorial Sloan Kettering Cancer Center - Main Campus	New York	New York
United States	Memorial Sloan Kettering Cancer Center 53rd street.	New York	New York
United States	Memorial Sloan Kettering Cancer Center 53rd street.	New York	New York
United States	UPMC Hillman Cancer Center	Pittsburgh	Pennsylvania
United States	Oregon Health & Science University (OHSU)	Portland	Oregon
United States	Oregon Health and Science University - Center for Health and Healing 1 (CHH1)	Portland	Oregon
United States	Oregon Health and Science University - Center for Health and Healing 2(CHH2)	Portland	Oregon
United States	Sarcoma Oncology Research Center	Santa Monica	California
United States	Moffitt Cancer Center	Tampa	Florida
United States	MSK Nassau	Uniondale	New York

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	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)
Primary	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.	Baseline up to safety FU visit ((Up to approximately 17 months)
Primary	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.	Baseline up to safety FU visit (Up to approximately 17 months)
Primary	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.	Baseline up to safety FU visit (Up to approximately 17 months)
Primary	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.	First dose to last dose (Up to approximately 16 months)
Primary	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.	Initiation of treatment up to progression or initiation of new anti-cancer therapy or discontinuation from study (Up to approximately 20 months)
Primary	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.	Baseline up to safety FU visit (Up to approximately 17 months)
Secondary	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.	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)
Secondary	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.	Baseline up to safety FU visit (Up to approximately 20 months)
Secondary	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.	Baseline up to safety FU visit (Up to approximately 20 months)
Secondary	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.	Baseline up to safety FU visit (Up to approximately 20 months)
Secondary	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.	First dose to last dose (Up to approximately 20 months)
Secondary	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.	Initiation of treatment up to progression or initiation of new anti-cancer therapy or discontinuation from study (Up to approximately 20 months)
Secondary	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.	From initiation of treatment until discontinuation from study (Up to approximately 29 months)
Secondary	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.	Initiation of treatment up to progression or initiation of new anti-cancer therapy or discontinuation from study (Up to approximately 20 months)
Secondary	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.	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)
Secondary	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.	Initiation of treatment up to progression or initiation of new anti-cancer therapy or discontinuation from study (Up to approximately 20 months)
Secondary	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.	Initiation of treatment up to progression or initiation of new anti-cancer therapy or discontinuation from study (Up to approximately 20 months)
Secondary	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.	Initiation of treatment up to progression or initiation of new anti-cancer therapy or discontinuation from study (Up to approximately 20 months)
Secondary	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.	Baseline up to safety FU visit (Up to approximately 20 months)
Secondary	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.	Baseline up to safety FU visit (Up to approximately 20 months)
Secondary	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.	Baseline up to safety FU visit (Up to approximately 20 months)

External Links

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