A phase I/IIa, multicenter, open-label Investigator Initiated Trial of anti-periostin antibody PT0101 in patients with advanced solid cancers and HER2-negative recurrent or metastatic breast cancer.

JRCT ID: jRCT2051240263

Registered date:06/02/2025

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Advanced solid cancers, HER2-negative recurrent or metastatic breast cancer
• Date of first enrollment: 06/02/2025
• Target sample size: 80
• Study type: Interventional

Intervention(s)

<Phase I monotherapy part>
PT0101 will be administered twice every 14 days. In principle, 4 weeks (28 days) will be regarded as 1 cycle. PT0101 will be administered for a maximum of 6 cycles, unless patients meet the criteria for discontinuation.

<Phase I combination therapy part>
PT0101 (at a dose of 10 or 3mg/kg) will be administered in combination with paclitaxel, twice every 14 days. In principle, 1cycle is defined as 28 days, and this will be administered for a maximum of 6 cycles unless patients meet the criteria for discontinuation.

<Phase IIa part>
PT0101(The recommended dose determined in the Phase I combination part) will be administered in combination with paclitaxel every 14 days. PT0101 will be administered on Day 1 and Day 15, and paclitaxel will be administered on Day 1, Day 8, and Day 15. In principle, 1cycle is defined as 28 days, and this will be administered for a maximum of 6 cycles unless patients meet the criteria for discontinuation.

Outcome(s)

Primary Outcome

<Phase I monotherapy part>
-Adverse events and their frequencies that occurred with each dose when PT0101 is administered as a single agent.
-DLT of PT0101 administered as a single agent
-MTD of PT0101 administered as a single agent

<Phase I combination part>
-Adverse events and their frequencies that occurred with each dose when PT0101 is administered in combination with paclitaxel.
-DLT of PT0101 administered in combination with paclitaxel
-MTD of PT0101 administered in combination with paclitaxel

<Phase IIa part>
-Response rate of PT0101 in combination with paclitaxel as assessed by the physician acccording to RECIST v1.1. (complete response:CR, partial response:PR)

Secondary Outcome

<Phase I monotherapy part and Phase I combination part>
-Overall survival and its rate
-Progression-free survival
Response ratio (CR, PR) assessed by the physician according to RECIST v1.1.
-Disease control rate (CR, PR, stabe disease:SD) assessed by the physician according to RECIST v1.1.
-Changes in blood concentration of PT0101 by dose
-Changes in blood Periostin concentration by dose
-Changes in tumor marker by dose (Change from baseline)
-Changes in pharmacodynamic markers by dose (Change from baseline)

<Phase IIa part>
-Disease control rate (CR, PR, SD) assessed by the physician according to RECIST v1.1.
-Overall survival and its rate
-Progression-free survival
-Changes in blood concentration of PT0101 by dose
-Changes in blood Periostin concentration by dose
-Changes in tumor marker by dose (Change from baseline)
-Changes in pharmacodynamic markers by dose (Change from baseline)

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

<Phase I monotherapy part>
1. Patients who have voluntarily provided written informed consent for participation in the study
2. Patients aged 18 years or older at the time of providing informed consent
3. No standard treatment or completed standard treatment (refractory or intolerant to standard treatment)
4. Patients with pathologically (histologically or cytologically) diagnosed as solid tumor, also with unresectable local lesion or metastatic lesion
5. Patients with Eastern Cooperative Oncology Group (ECOG) performance status(PS) 0 or 1
6. 21 days or more have passed since the last dose of anti-tumor agents at the time of enrollment
7. 21 days or more have passed since the last irradiation of radiation therapy at the time of enrollment
8. Patients who have AEs due to previous anticancer therapies must have recovered to Grade <=1 (except for alopecia Grade2 peripheral neuropathy) according to CTCAE v5.0
9. Patients must have following adequate bone marrow functions:
-Neutrophil count >= 1,500/mm3 (growth factor independent)
-Platelets >= 100,000/mm3 (growth factor or transfusion independent)
-Hemoglobin >= 9g/dL (growth factor or transfusion independent)
10. Patients must have following adequate liver function:
-Bilirubin <= 2.25mg/dL
-ALT and AST <= 75 U/L (if liver metastases are present, <=150 U/L)
-Serum albumin >= 3.0 g/dL
11. Patients must have following adequate kidney function:
-eGFR>=40 mL/min/1.73 m2
12. Patients can be taken intervenous accesses (including central venous catheter ports) suitable for the collection of blood samples required for the study, including for pharmacokinetic evaluation

<Phase I combination therapy part>
1. Patients who have voluntarily provided written informed consent for participation in the study
2. Patients aged 18 years or older at the time of providing informed consent
3. No standard treatment or completed standard treatment(refractory or intolerant to standard treatment)
4. Patients with pathologically (histologically or cytologically) diagnosed as solid tumor, also with unresectable local lesion or metastatic lesion
5. Patient with ECOG PS 0 or 1
6. 21 days or more have passed since the last dose of anti-tumor agents at the time of enrollment
7. 21 days or more have passed since the last irradiation of radiation therapy at the time of enrollment
8. Patients who have AEs due to previous anticancer therapies must have recovered to Grade <=1 (except for alopecia) according to CTCAE v5.0
9. Patients must have following adequate bone marrow function:
-Neutrophil count >= 1,500/mm3 (growth factor independent)
-Platelets >= 100,000/mm3 (growth factor or transfusion independent)
-Hemoglobin >= 9g/dL (growth factor or transfusion independent)
10. Patients must have following adequate liver function:
-Bilirubin <= 2.25mg/dL
-ALT and AST <= 75 U/L (if liver metastases are present, <=150 U/L)
-Serum albumin >= 3.0 g/dL
11. Patients must have following adequate kidney function:
-eGFR>=40 mL/min/1.73 m2
12. Patients can be taken intervenous accesses (including central venous catheter ports) suitable for the collection of blood samples required for the study, including for pharmacokinetic evaluation

<Phase IIa part>
1. Patients who have voluntarily provided written informed consent for participation in the study
2. Patients aged 18 years or older at the time of providing informed consent
3. Patients who have been received more than one regimen of chemotherapy for HER2-negative metastatic or recurrent breast cancer (excluding patients who have been received any taxanes (PTX, nab-PTX, DTX) as treatment for metastasis or recurrent breast cancer. If taxanes were used during neoadjuvant or adjuvant therapy and recurrence occurred within 12 months after the completion of the neoadjuvant or adjuvant therapy, it is considered to be the use of taxanes for metastasis or recurrent breast cancer)
4. Patients who have been pathologically (histologically or cytologically) diagnosed with HER2-negative breast cancer
5. Patients with unresectable local lesion or distant metastatic lesion, and with measurable lesion according to RECIST v.1.1
6. Patients with ECOG PS 0 or 1
7. 21 days or more have passed since the last dose of anti-tumor agents at the time of enrollment
8. 21 days or more have passed since the last irradiation of radiation therapy at the time of enrollment
9. Patients who have AEs due to previous anticancer therapies must have recovered to Grade <=1 (except for alopecia) according to CTCAE v5.0
10. Patients must have following adequate bone marrow function:
-Neutrophil count >= 1,500/mm3 (growth factor independent)
-Platelets >= 100,000/mm3 (growth factor or transfusion independent)
-Hemoglobin >= 9g/dL (growth factor or transfusion independent)
11. Patients must have following adequate liver function:
-Bilirubin <= 2.25mg/dL
-ALT and AST <= 75 U/L (or <=150 U/L if due to liver involvement by tumor)
-Serum albumin >= 3.0 g/dL
12. Patients must have following adequate kidney function:
-eGFR>=40 mL/min/1.73 m2
13. Patients can be taken intervenous accesses (including central venous catheter ports) suitable for the collection of blood samples required for the study, including for pharmacokinetic evaluation

Exclude criteria

<Phase I monotherapy part>
1. Patients with interstitial lung disease/pneumonitis (including radiation pneumonitis)
2. Patients with primary brain tumors or central nervous system metastases, either active or inactive
3. Patients with multiple cancers (simultaneous or metachronous with disease-free interval of 2 years or less from the registration date), except for carcinoma in situ and non-invasive cancers
4. Patients with active infection requiring systemic treatment
5. Patients who are positive for HBV, HCV, or HIV
6. Patients with heart failure Class II -IV according to NYHA Classification, or history of heart failure Class III or IV according to NYHA Classification
7. Patients who have a history or complication of ischemic heart disease, arrhythmias requiring treatment
8. Patients who have a history or complication of cerebrovascular or cardiovascular impairment, thromboembolism, or sudden cardiac arrest, requiring treatment
9. Patients with uncontrolled diabetes mellitus
10. Patients with uncontrolled hypertension (over systolic blood pressure 160mmHg and diastolic blood pressure 100mmHg)
11. Patients with pleural effusion, ascites, or pericardial effusion requiring regular drainage
12. Women of childbearing potential (i.e., those who have not undergone permanent sterilization and are premenopausal) who intend to become pregnant, pregnancy, lactation. Patients judged to be pregnant by investigator are ineligible because it is possible that a pregnancy test may not show a positive result in early pregnancy.
13. Patients with a history of hypersensitivity to PT0101
14. Used any investigational product within 90 days prior to informed consent
15. Patients with highly invasive surgical intervention within 14 days prior to entry
16. Patients who are receiving any investigational study or interventional clinical study, or who are planning to join any other study during this study
17. Patients who are deemed by the investigator to be inappropriate to participate in this study

<Phase I combination therapy part>
1. Patients with interstitial lung disease/pneumonitis (including radiation pneumonitis)
2. Patients with primary brain tumors or central nervous system metastases, either active or inactive
3. Patients with multiple cancers (simultaneous or metachronous with disease-free interval of 2 years or less from the registration date), except for carcinoma in situ and non-invasive cancers
4. Patients with active infection requiring systemic treatment
5. Patients who are positive for HBV, HCV, or HIV
6. Patients with heart failure Class II -IV according to NYHA Classification, or history of heart failure Class III or IV according to NYHA Classification
7. Patients who have a history or complication of ischemic heart disease, arrhythmias requiring treatment
8. Patients who have a history or complication of cerebrovascular or cardiovascular impairment, thromboembolism, or sudden cardiac arrest, requiring treatment
9. Patients with uncontrolled diabetes mellitus
10. Patients with uncontrolled hypertension (over systolic blood pressure 160mmHg and diastolic blood pressure 100mmHg)
11. Patients with pleural effusion, ascites, or pericardial effusion requiring regular drainage
12. Women of childbearing potential (i.e., those who have not undergone permanent sterilization and are premenopausal) who intend to become pregnant, pregnancy, lactation. Patients judged to be pregnant by investigator are ineligible because it is possible that a pregnancy test may not show a positive result in early pregnancy.
13. Used any investigational product within 90 days prior to informed consent
14. Patients with highly invasive surgical intervention within 14 days prior to entry
15. Patients who are receiving any investigational study or interventional clinical study, or who are planning to join any other study during this study
16. Patients with a history of allergy to PT0101, PTX or other taxanes
17. Patients with alcohol intolerance (Excluding skin hypersensitivity reactions)
18. Patients who are deemed by the investigator to be inappropriate to participate in this study

<Phase IIa part>
1. Patients with interstitial lung disease/pneumonitis (including radiation pneumonitis)
2. Patients with central nervous system metastases, either active or inactive
3. Patients with multiple cancers (simultaneous or metachronous with disease-free interval of 2 years or less from the registration date), except for carcinoma in situ and non-invasive cancers
4. Patients with active infection requiring systemic treatment
5. Patients who are positive for HBV, HCV, or HIV
6. Patients with heart failure Class II -IV according to NYHA Classification, or history of heart failure Class III or IV according to NYHA Classification
7. Patients who have a history or complication of ischemic heart disease, arrhythmias requiring treatment
8. Patients who have a history or complication of cerebrovascular or cardiovascular impairment, thromboembolism, or sudden cardiac arrest, requiring treatment
9. Patients with uncontrolled diabetes mellitus
10. Patients with uncontrolled hypertension (over systolic blood pressure 160mmHg and diastolic blood pressure 100mmHg)
11. Patients with pleural effusion, ascites, or pericardial effusion requiring regular drainage
12. Women of childbearing potential (i.e., those who have not undergone permanent sterilization and are premenopausal) who intend to become pregnant, pregnancy, lactation. Patients judged to be pregnant by investigator are ineligible because it is possible that a pregnancy test may not show a positive result in early pregnancy.
13. Used any investigational product within 90 days prior to informed consent
14. Patients with highly invasive surgical intervention within 14 days prior to entry
15. Patients who are receiving any investigational study or interventional clinical study, or who are planning to join any other study during this study
16. Patients with a history of allergy to PT0101, PTX or other taxanes
17. Patients with alcohol intolerance (Excluding skin hypersensitivity reactions)
18. Patients who are deemed by the investigator to be inappropriate to participate in this study

Related Information

• Primary Sponsor: Shimazu Kenzo
• Source(s) of Monetary Support: Periotherapia Co.,Ltd,Japan Agency for Medical Research and Development