Pyrotinib Plus Thalidomide in Advanced NSCLC Patients Harboring HER2 Exon 20 Insertions

NCT04382300 | Unknown Phase 2

• 1 other identifier: MA-NSCLC-II-005
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

Brief Summary

Various driver gene mutations have been identified in lung cancer. Among them, human epidermal growth factor 2 (HER2) was identified in approximately 2% of non-small-cell lung cancers. Pyrotinib is an oral tyrosine kinase inhibitor targeting both HER-1 and HER-2 receptors. This is a prospective, single-arm, open-label phase II study, designed to evaluate the efficacy and safety of pyrotinib combined with thalidomide in advanced non-small-cell lung cancer patients with HER2 exon 20 insertions.

Conditions

Non-small-cell Lung Cancer

Keywords

Pyrotinib; HER2; Non-small-cell Lung Cancer; Phase II; Thalidomide

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate

  The proportion of patients with complete response or partial response.

  24 months

Secondary Outcomes (6)

• Progression-free Survival

  24 months

• Overall Survival

  24 months

• Disease Control Rate

  24 months

• Incidence of Adverse Events

  24 months

• Changes in Scores of European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30)

  24 months

Study Arms (1)

Treatment arm

EXPERIMENTAL

pyrotinib 400mg p.o. qd, combined with thalidomide 200mg p.o. qd

Drug: pyrotinib combined with thalidomide

Interventions

pyrotinib combined with thalidomide DRUG

Single Group Assignment

Treatment arm

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 18-80 years.
• ECOG performance status 0-1.
• Life expectancy ≥12 weeks.
• At least one measurable lesion according to RECIST 1.1.
• Histologically or cytologically confirmed advanced (IIIB or IV) non-small-cell lung cancer according to the 7th edition of TNM classification and staging system for lung cancer published by IASLC.
• HER2 exon 20 insertions confirmed by next generation sequencing or polymerase chain reaction (if blood samples are used, the mutation abundance should be ≥10%).
• Disease progression during or after platinum-based chemotherapy, or refusing chemotherapy (patients are allowed to have prior therapy with PD-1/PD-L1 inhibitors and/or antiangiogenic agents).
• No more than two prior chemotherapy regimens (a. replacing platinum drug due to toxicity is considered as a new regimen; b. adjuvant chemotherapy is not considered as a prior regimen if disease recurrence occurred at more than 6 months after the last dose).
• No radiotherapy within 3 months, or prior radiotherapy with radiation area \<25% of bone marrow area at least 4 weeks before enrollment.
• Required laboratory values including following parameters:
• ANC: ≥ 1.5 × 10\^9/L, Platelet count: ≥ 90 × 10\^9/L, Hemoglobin: ≥ 90 g/L, INR: ≤1.5, APTT: ≤1.5 × ULN, Total bilirubin: ≤ 1.5 × ULN, ALT and AST: ≤ 2 × ULN for liver metastases, BUN and creatine: ≤ 1.5 × ULN, creatine clearance rate: ≥ 50 mL/min, LVEF: ≥ 50%, QTcF: \< 470 ms for female, \< 450 ms for male.
• Willingness to use highly effective contraception from the start of the study to 90 days after the last dose of study drug.
• Written informed consent.

You may not qualify if:

• Prior HER2-targeting therapies.
• Other gene alterations with available targeted drugs, such as EGFR mutations, T790M resistance mutations, ALK fusions, ROS1 fusions, RET rearrangements, BRAF V600E mutations, NTRK fusions, and MET exon 14 skipping.
• Factors influencing the oral administration of drugs, such as inability to swallow, chronic diarrhea, intestinal obstruction, or other gastrointestinal diseases or abnormalities.
• With third space effusion that can not be controlled by drainage or other methods.
• Radiotherapy, chemotherapy, surgery, or other targeted therapy for non-small-cell lung adenocarcinoma within 4 weeks.
• Active brain metastases, meningeal metastases, spinal compression, or CT or MRI revealing brain or leptomeningeal diseases at screening (patients with symptomatically stable brain metastases can be enrolled if no cerebral hemorrhage is found by brain MRI, CT or venography).
• Uncontrolled hypokalemia or hypomagnesemia.
• Allergy history to the components of study drug.
• History of immunodeficiency disease (including positive test of human immunodeficiency virus, active hepatitis B/C, or other acquired or congenital immunodeficiency disease) or organ transplantation.
• History of cardiac diseases, including angina, arrhythmia requiring drug therapy or of clinical significance, myocardial infarction, heart failure, and other cardiac diseases unsuitable for this trial as judged by the investigator.
• Patients with thrombotic disease or previous history of thrombosis.
• Other malignancies within 5 years, except for cured cervical cancer in situ, skin basal cell cancer, and skin squamous cell cancer.
• History of neurological or mental disorders, such as epilepsy and dementia.
• Respiratory syndrome (dyspnea ≥grade 2 using NCI CTCAE 5.0).
• Coagulation disorders (INR \>1.5, prothrombin time \>ULN + 4 s, or APTT \>1.5×ULN), with bleeding tendency or receiving thrombolytic or anticoagulant therapy.

Sponsors & Collaborators

• Shanghai Chest Hospital: lead

Study Sites (1)

Department of Oncology, Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University

Shanghai, 200030, China

RECRUITING

Related Publications (1)

• Ai X, Song Z, Jian H, Zhou Z, Chen Z, Yu Y, Li Z, Lu S. Pyrotinib combined with thalidomide in advanced non-small-cell lung cancer patients harboring HER2 exon 20 insertions (PRIDE): protocol of an open-label, single-arm phase II trial. BMC Cancer. 2021 Sep 16;21(1):1033. doi: 10.1186/s12885-021-08759-8.

  PMID: 34530760 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Thalidomide

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Central Study Contacts

Shun Lu

CONTACT

86-21-22200000; shunlu@sjtu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of the Oncology department

Study Record Dates

• First Submitted: April 30, 2020
• First Posted: May 11, 2020
• Study Start: June 30, 2020
• Primary Completion: October 1, 2022
• Study Completion: April 1, 2023
• Last Updated: January 28, 2021

Record last verified: 2021-01

Locations

CN (1)