A Study of Trastuzumab and Pyrotinib in HER2 Positive Locally Advanced or Metastatic Urothelial Carcinoma

Sponsor

Chinese Academy of Medical Sciences (Other)

Overall Status

Recruiting

CT.gov ID

NCT05318339

Collaborator

(none)

Enrollment

Location

Arm

33.1

Anticipated Duration (Months)

0.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

A open-label, single-arm, phase II trial to study was designed to evaluate the effectiveness and safety of trastuzumab and pyrotinib in treating HER2 positive patients who have previously treated, locally advanced, or metastatic urothelial carcinoma.

Condition or Disease	Intervention/Treatment	Phase
Carcinoma, Transitional Cell HER-2 Gene Amplification	Drug: Trastuzumab	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Open-label, Single-arm Phase II Study of Trastuzumab and Pyrotinib Combination Regimen in HER2 Positive Locally Advanced or Metastatic Urothelial Carcinoma Refractory to Standard Therapies

Actual Study Start Date :

Mar 10, 2022

Anticipated Primary Completion Date :

Mar 10, 2024

Anticipated Study Completion Date :

Dec 10, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Trastuzumab + Pyrotinib Patients receive a loading dose of trastuzumab IV over 90 minutes on day 1 of week 1. For all subsequent doses, patients receive trastuzumab IV over 30 minutes every three weeks. Meanwhile, patients also receive pyrotinib 400mg PO daily. Treatment may continue till unacceptable toxicity or disease progression occurs.	Drug: Trastuzumab A loading dose of trastuzumab 8mg/kg IV over 90 minutes will be administrated on day 1 of week 1. For all subsequent doses, trastuzumab 6mg/kg IV over 30 minutes will be administrated every three weeks. Pyrotinib 400mg PO daily will be administrated at the same time. Other Names: Pyrotinib

Arm

Intervention/Treatment

Experimental: Trastuzumab + Pyrotinib

Patients receive a loading dose of trastuzumab IV over 90 minutes on day 1 of week 1. For all subsequent doses, patients receive trastuzumab IV over 30 minutes every three weeks. Meanwhile, patients also receive pyrotinib 400mg PO daily. Treatment may continue till unacceptable toxicity or disease progression occurs.

Drug: Trastuzumab

A loading dose of trastuzumab 8mg/kg IV over 90 minutes will be administrated on day 1 of week 1. For all subsequent doses, trastuzumab 6mg/kg IV over 30 minutes will be administrated every three weeks. Pyrotinib 400mg PO daily will be administrated at the same time.

Other Names:

Pyrotinib

Outcome Measures

Primary Outcome Measures

ORR [1 year]
Objective response rate as assessed by RECIST criteria

Secondary Outcome Measures

OS [From date of initiation of treatment to date of death due to any cause, assessed up to 2 years]
Overall survival
PFS [From date of initiation of treatment to date of progression or death due to any cause, whichever occurs first, assessed up to 2 years]
Progression free survival

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Sign the informed consent form
Locally advanced or metastatic histologically confirmed transitional cell carcinoma of the urothelium, including the bladder, urethra, ureter, or renal pelvis
18 years and older
HER2 expression (3+ or 2+) as determined by immunohistochemistry or gene amplification by fluorescent in situ hybridization
Relapsed from or failed at least one prior standard systemic chemotherapy regimen, including immunotherapy, HER2 ADC durgs, and chemothearpy containing cisplatin, carboplatin, paclitaxel, docetaxel, or gemcitabine
At least 1 measurable lesion could be evaluated by RECIST v1.1
Performance status: ECOG 0-1
Life expectancy more than 12 weeks
Ejection fraction at least 50% (or lower limit of normal) by echocardiogram
Good organ function:

Blood routine: hemoglobin ≥80g/L, neutrophil ≥1.5×10^{9/L, platelet ≥75×10}9/L; Renal function: creatinine≤1.5×upper limit of normal (UNL) or creatinine clearance ≥50ml/min; Liver function: total bilirubin (TBIL)≤1.5×upper limit of normal (UNL); ALT≤2.5×UNL, AST≤2.5×UNL, ALT≤5×UNL and AST≤5×UNL for patients with liver metastasis

Exclusion Criteria:

Have received trastuzumab or pyrotinib treatment in the past
Known to have allergic reactions to any ingredients or excipients of experimental drugs
Radiotherapy, RFA, interventional therapy or surgery were performed within 28 days before the first medication (except for previous diagnostic biopsy)
Other active malignant tumors, excluding those who have been disease free for more than 5 years or in situ cancer considered to have been cured by adequate treatment
Clinically significant ascites
Brain metastasis or meningeal metastasis with neurological symptoms
Diabetes was not controlled, defined as HbA1c > 7.5% after anti-diabetic drugs or hypertension was not controlled, defined as systolic / diastolic blood pressure > 140 / 90 mmHg after antihypertensive drug
Myocardial infarction, severe/unstable angina, New York Heart Association (NYHA) class III or IV congestive heart failure in the past 12 months
Known to be infected with human immunodeficiency virus (HIV), have acquired immunodeficiency syndrome (AIDS) related diseases, have active hepatitis B or hepatitis C
Pregnant or nursing
May increase the risk associated with participation in the study or administration of the study drug or mental illness that may interfere with the interpretation of research results
There are other serious diseases that the researchers believe patients cannot be included in the study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College	Beijing		China

Sponsors and Collaborators

Chinese Academy of Medical Sciences

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Aiping Zhou, Vice director of Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences

ClinicalTrials.gov Identifier:

NCT05318339

Other Study ID Numbers: