TEMENOS2

JRCT ID: jRCT2031210436

Registered date:21/11/2021

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: HER2-positive advanced paget disease affecting scrotum and Penis
• Date of first enrollment: 16/05/2022
• Target sample size: 14
• Study type: Interventional
• Intervention(s): Eligible patients receive trastuzumab emtansine 3.6mg/kg Q3W. The treatment period will continue every 21 days for up to 2 years as long as subjects are receiving benefit from treatment and have not had disease progression or met any criteria for study withdrawal. Study participants will be assessed for a tumour response every 6 or 9 week by imaging. Each patient will be followed up on safety until 4 weeks after the end of treatment, or until 15 days after the day of the study withdrawal, or until start of other treatment.

Outcome(s)

Primary Outcome

Response rate (central judgment)
Evaluation according to RECIST Guidelines 1.1 version

Secondary Outcome

1) Efficacy evaluation items
/ Response rate (judgment by a doctor at the medical institution) Evaluation according to RECIST Guidelines 1.1 version
/ Response rate at 6 months, 1 year, and 2 years
/ Progression-free survival
/ Overall survival
/ Disease control rate
/ Rate of change in tumor size
/ Response duration
/ Time to response
/ Full treatment period
/ Number of treatment cycles
2) Safety evaluation items
/ Type, frequency and severity of adverse events (CTCAE ver. 5. 0)
/ Type, frequency and severity of side effects (CTCAE ver. 5.0)

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: <= 80age old
• Gender: Both

Include criteria

(1) Patients who have received sufficient explanation about the content of the trial and have obtained written consent.
(2) Patients whose age at the time of obtaining consent is 20 to 80 years old.
(3) Patients with Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 to 1.
(4) Patients who have histologically confirmed as extramamary Paget's disease.
(5) Patients who have HER2-positive (IHC 3+ or ISH-positive) tumor tissue (primary, recurrent or metastatic lesion) confirmed by central pathological review and ISH analysis.
(6) Patients who have unresectable or metastatic extramammary Paget's disease
(7) Patients who have one or more measurable lesions (excluding primary lesions) defined in RECIST Guidelines Version 1.1 by imaging within 14 days prior to enr ollment
(8) Patients who have laboratory parameters within Protocol-defined range. The screening laboratory tests below must be done within 14 days before registration.
-Neutrophil count >= 1,500/mm3
-Platelets >= 100,000/mm3
-Hemoglobin >= 9.0g/dl
-Aspartate aminotransferase (AST), alanine aminotransferase (ALT) <= 2.5X upper limit of normal (ULN)
-Alkaline phosphatase (ALP) v2.5X upper limit of normal (ULN)
-Total bilirubin <= 1.5X ULN
-Serum creatinine <= 1.5mg/dl
-Prothrombin (INR) and APTT <= 1.5X ULN
(9) Patients who have not been treated with HER2 inhibitors including trastuzumab emtansine.

Exclude criteria

(1) Patients who have clinically significant cardiac disease as follows:
- Grade 3 (CTCAE 5.0) or worse cardiac dysfunction or that specified in New York Heart Association (NYHA) classification class II to IV
- unstable angina pectoris, cardiac failure, myocardial infarction, or ventricular arrhythmia requiring medical treatment within the 6 months prior to registration
(2) Patients who have uncontrolled hypertension at the time of registration.
(3) Patients who have left ventricular ejection fraction (LVEF) of less than 50% by echocardiography within 28 days prior to registration.
(4) Patients who had been taken cumulative doxorubicin doses exceeding 500 mg/m2, or patients who had been other anthracycline drugs exceeding the equal cumulative dose (epirubicin: 900 mg / m2 or less, aclarubi cin: 600 mg or less, daunorubicin: 25 mg / kg or less, pirarubicin: 950 mg / m2 or less, mitoxantrone: 160 mg / m2 or less).
(5) Patients who have a history of hypersensitivity to the ingredients or additives of the study drug (sodium succinate, sucrose, polysorbate 20).
(6) Patients who have brain metastasis which meet any of the following conditions.
- Have untreated or treatment-required brain metastases at the time of registration.
- Have clinical symptoms within 60 days before registration
- Have a history of treatment for brain metastases (including corticosteroids) within 60 days before registration.
- Have clinical deteriorarion or disease progression confirmed by imaging even after lesional therapy for brain metastases.
(7) Patients who require continuous oxygen therapy.
(8) Patients who have interstitial lung disease (pneumonitis, interstitial pneumonia, etc.) or a history of them.
(9) Patients who have Grade 3 or worse peripheral neuropathy.
(10) Patients taking bisphosphonates for malignant paraneoplastic hypercalcemia (excluding the use of that for other reasons such as osteopor osis and bone metastasis)
(11) Patients who received chemotherapy, hormone therapy, radia
tion therapy, immunotherapy or biological therapy for extramammary Paget's disease within 3 weeks prior to registration.
(12) Patients whose toxicity associated with palliative radiation therapy has not recovered to the grade before radiation therapy within 2 weeks before registration.
(13) Patients who received other investigational or clinical study drugs within 4 weeks prior to registration.
(14) Patients who have not recovered from adverse effects of surgical treatment (excluding biopsy) or significant trauma within 4 weeks prior to enrollment or who require surgical treatment during the study period.
(15) Additional malignancy that is progressing or requires active treatment. Exceptions include cancers that have not recurred for at least 5 years before enrollment on study and early-stage cancers (carcinoma in situ) treated with curative intent, basal cell carcinoma of the skin that has undergone potentially curative therapy.
(16) Pregnant women, breastfeeding woman and woman with a positive for pregnancy test. Patients who are not willing to use contraceptives during the study period and 7 months the last dose of the study drug.
(17) Seropositive for hepatitis B antigen, or hepatitis C antibody.
Even if negative for HBs antigen, patients who are positive for HBs antibody or HBc antibody and amount of HBV-DNA exceed detection sensitivity are excluded from the study.
(18) Patients who have known history of HIV.
(19) Be determined as being an inappropriate study case by the trial responsibility physicians or trial allotment physicians.

Related Information

• Primary Sponsor: Funakoshi Takeru
• Source(s) of Monetary Support: Japan Agency for Medical Research and Development