An Exploratory Basket Study of Pyrotinib Maleate Tablets in HER2 Mutated or Amplified of Metastatic Solid Tumors

A single arm, open-label Phase II clinical study.The subjects were patients with lung, gastric and colorectal cancers.

Study Overview

• Status: Not yet recruiting
• Conditions: Solid Tumor
• Intervention / Treatment: Drug: Pyrotinib Maleate; Other: standard regimen

Detailed Description

Object: 1.The main purpose: T To observe and evaluate the efficacy of pyrotinib in patients with HER2-mutated/amplified metastatic solid tumors after failure of standard therapy; 2. Secondary objectives: To observe and evaluate the safety of pyrotinib in patients in HER2 mutated or amplified metastatic solid tumors after failure of standard treatment.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Li Xiao, Phd; Phone Number: 13906036392; Email: xiaolibohan@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age:18-75 years old, regardless of gender;
2. Disease progression during the previous standard treatment or disease progression within 6 months after the end of treatment, patients with gastric and gastroesophageal junction adenocarcinoma requires previous use of trastuzumab, and other tumors must have received at least first-line standard chemotherapy ± targeted therapy.
3. Two or more grade IV hematological toxicity or non-hematological toxicity ≥ grade III or damage to the heart, liver, kidney and other major organs of grade ≥ II occurred during the standard treatment process; Patients who have been confirmed by the doctor to no longer receive standard treatment can be included in the group.
4. HER2 mutated non-small cell lung cancer , gastric and gastroesophageal junction adenocarcinoma or Adenocarcinoma of the colon has been confirmed by Pathology.
5. Cancer tissue pathology is clearly HER2 positive: including IHC2+/ISH+, IHC 3+ or HER2 mutations (the results obtained by NGS method, PCR method, Sanger method, mass spectrometry sequencing and other measurement methods are all acceptable).
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1;
7. For recurrent or metastatic tumours, according to the RECIST 1.1 standard, the subject has at least one measurable target disease.
8. Life expectancy greater than or equal to 12 months;
9. The functional level of organs must meet the following requirements:

(1) Blood routine: ANC ≥ 1.5×10^9/L; PLT ≥ 90×10^9/L; Hb ≥ 90 g/L; (2) Blood biochemistry: TBIL<=1.5×ULN; ALT and AST<=2×ULN; for subjects with liver metastases, ALT and AST<=5×ULN; BUN and Cr<=1.5×ULN and creatinine clearance ≥50mL/min (Cockcroft-Gault formula); (3) Heart color Doppler ultrasound: LVEF≥50%; (4) 12-lead electrocardiogram: The QT interval (QTcF) corrected by Fridericia's method is <450ms for males and <470ms for females.

10. Have sufficient bone marrow, liver and kidney functions. 11. Women of childbearing age and their spouses are willing to contraception during treatment and within 1 year after the last medication.

Volunteer to join the study, sign an informed consent form, have good compliance and are willing to cooperate with follow-up.

Exclusion Criteria:

• 1. Left ventricular ejection fraction (LVEF) < 50% at baseline (measured by echocardiography or MUGA); 2. Patients who have received systemic therapy including immunotherapy, biotherapy and any clinical trial drugs in the past 2 weeks; 3. Patients with uncontrollable central metastases, brain tumor lesions confirmed by brain CT or MRI and need dehydration treatment or radiotherapy (except for patients with stable brain metastases after 1 month of radiotherapy); 4. With > grade 1 unresolved toxicity due to any previous treatment / procedure (ctc-ae, except alopecia, anemia, and hypothyroidism); 5. Severe infection and other serious systemic diseases; 6. Patients receiving long-term or high-dose corticosteroid treatment (inhaled steroids or short-term oral steroids are allowed to resist vomiting or promote appetite); 7. Evidence or history of coagulation disorders such as bleeding events with grade ≥ 3 (ctc-ae); 8. Patients whom intestinal obstruction and other factors affecting oral administration or absorption of drugs; After the comprehensive judgment of the disease, the researcher thought that it was not suitable to participate in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: A single arm, open-label Phase II clinical study.; All subjects enrolled will receive the following treatment：Pyrotinib±standard treatment. Pyrotinib 400 mg/ D (once a day, at the same time each day) until the progression of disease; Chemotherapy regimens follow the programme cycle recommended by the guidelines or as determined by the investigator. The dosage can be adjusted according to the protocol according to the adverse reactions of subjects. Subjects will continue to take medication until completion of the prescribed course of treatment, disease progression, toxicity intolerance, withdrawal of Informed Consent Form, or termination in the investigator's judgment.

Drug: Pyrotinib Maleate; Pyrotinib ± standard regimen Pyrotinib: 400 mg/day (once a day, orally at the same time every day), continued until disease progression; Other: standard regimen; standard regimen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate	Defined as proportion of complete response and partial response according to RECIST 1.1 criteria.	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Defined as the time from the date of informed consent until to the date of death, regardless of the cause of death.	24 months
Disease control rate	the proportion of patients whose tumors shrink or remain stable for a certain period of time, including complete remission (CR), partial remission (PR) and stable (SD) cases	24 months
Progression-free survival	Defined as the time from the date of informed consent to first documented disease progression (PD) using Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) or death from any cause, whichever occurred first.	24 months

Collaborators and Investigators

• Sponsor: Zhongshan Hospital Xiamen University
• Investigators: Principal Investigator: li xiao, Zhongshan Hospital Affiliated to Xiamen University

Study record dates

Study Major Dates

• Study Start (Anticipated): March 4, 2022
• Primary Completion (Anticipated): March 15, 2022
• Study Completion (Anticipated): March 15, 2024

Study Registration Dates

• First Submitted: March 2, 2022
• First Submitted That Met QC Criteria: March 9, 2022
• First Posted (Actual): March 10, 2022

Study Record Updates

• Last Update Posted (Actual): March 10, 2022
• Last Update Submitted That Met QC Criteria: March 9, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: HER2 mutation or amplification,Pyrotinib
• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Maleic acid
• Other Study ID Numbers: 2022-228

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No