SafetyPhase 2APPEARNCT04785729
Almonertinib Combined With Pyrotinib in the Treatment of Advanced NSCLC Patients With HER-2 Amplification/Mutation After EGFR-TKI Resistance
A Phase 2 study testing Almonertinib combine with Pyrrolitinib in people with Safety, run by Sun Yat-sen University at 1 site in China.
Trial summary
This is a multicenter, open, phase II clinical trial to evaluate the safety and efficacy of almonertinib combined with pyrrolitinib in locally advanced or metastatic NSCLC patients with her-2 variants detected after first-line EGFR-TKI treatment resistance. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Safety
- What is being tested?
- Almonertinib combine with Pyrrolitinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 1 siteChina
- Study dates
- 31 Dec 2020to Dec 2023
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 1. 18 ≤ age ≤75, regardless of gender. 2. Non-squamous NSCLC (including stage IIIB-IV patients who relapsed after previous surgical treatment or were newly diagnosed). According to AJCC edition 8 lung cancer Staging Criteria) 3. Previous treatment with EGFR-TKI (not limited to algebra) and radiographic disease progression were permitted with less than or equal to first-line chemotherapy.
- 4. Before inclusion in this study (after the last treatment), tumor tissues or blood samples were detected with EGFR-sensitive 19 exon deletion or L858R mutation (with or without T790M), and her-2 mutation (including sensitive mutation or amplification, in which amplification should be confirmed by FISH).
- 5. The Eastern Tumor Tissue Cooperative Group (ECOG) physical status score was 0 or 1 and did not deteriorate in the previous 2 weeks, with a minimum expected survival of 12 weeks.
- 6. The patient had at least one tumor lesion that had not received previous local treatment such as irradiation, nor had he received biopsy during the screening period, and it could be accurately measured at baseline, with the longest diameter ≥ 10mm at baseline (short diameter ≥ 15mm for lymph nodes). The measurement method chosen is suitable for accurate repeated measurements and can be computed tomography (CT) or magnetic resonance imaging (MRI). If there is only one measurable lesion and no previous local treatment such as irradiation, it may be accepted as the target lesion, and a baseline evaluation of the tumor lesion shall be conducted at least 14 days after the diagnostic biopsy.
- 7. For fertile women, appropriate contraception should be used and breastfeeding should not be performed for 3 months from screening to discontinuation of study treatment. A pregnancy test is negative before administration, or there is no proven risk of pregnancy if one of the following criteria is met: A. Postmenopause is defined as amenorrhea over the age of 50 and at least 12 months after cessation of all exogenous hormone replacement therapy.
- Women younger than 50 years of age may also be considered postmenopausal if they stop all exogenous hormone therapy for 12 months or more and their luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels are within the laboratory post-menopausal reference range.
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- Has undergone irreversible sterilization, including hysterectomy, bilateral oophorectomy or bilateral salpingectomy, except for bilateral tubal ligation.
- 8. Male patients should use barrier contraception (i.e., condoms) from screening until 3 months after treatment is discontinued.
- 9. The subject is willing to participate and sign the informed consent in person.
Who cannot join
- 1. Received any of the following treatments: A. Patients had undergone major surgery within 4 weeks before the first administration of the study drug; B. Received more than 30% of bone marrow irradiation or extensive radiotherapy within 4 weeks before the first administration of the drug; C. Within 7 days before the first administration of the study drug, CYP3A4 inhibitory agent, inducer or drug with narrow therapeutic window for CYP3A4 sensitive substrate was used.
- 2. Patients with other malignancies requiring standard treatment or major surgery within 2 years of the first administration of the treatment under study.
- 3. At the time of initiation of treatment, there was residual toxicity from previous treatment that was not alleviated, greater than CTCAE level 1, except for hair loss and level 2 neurotoxicity caused by previous chemotherapy.
- 4. Spinal cord compression or brain metastases, unless asymptomatic, stable, and not requiring steroid therapy at least 2 weeks prior to the first administration of the study treatment.
- 5. At the investigator's discretion, there were any serious or poorly controlled systemic diseases, such as poorly controlled hypertension, active bleeding constitutions, or active infections. There is no need to screen for chronic diseases.
- 6. Refractory nausea, vomiting, or chronic gastrointestinal disease, inability to swallow research drugs, or a history of extensive bowel resection, may interfere with adequate absorption of amitinib.
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- 7. Meet any of the following cardiac examination results: A. mean correction of QT interval (QTc) > 470 msec obtained by 3 electrocardiogram (ECG) examinations in resting state, and QT interval correction (QTcF) was performed using Fridericia formula; B. The resting ECG indicated a variety of clinically significant rhythms and morphological abnormalities in the conduction or ECG (such as complete left bundle branch block, degree 3 atrioventricular block, degree 2 atrioventricular block, and PR interval > 250 msec).
- Presence of any factor that increases the risk of prolonged QTc or arrhythmia events, such as heart failure, hypokalemia, congenital long QT syndrome, a family history of long QT syndrome, or sudden unexplained death in immediate family members under 40 years of age, or any combination of medications that prolong the QT interval; D. Left ventricular ejection fraction (LVEF) ≤40%. 8. A history of interstitial lung disease, a history of drug-induced interstitial lung disease, a history of radiation pneumonia requiring steroid treatment, or any evidence of clinically active interstitial lung disease.
- 9. Insufficient bone marrow reserve or organ function to achieve the following laboratory limits: A. Absolute neutrophil count <1.5×109 / L; B. Platelet count <100×109 / L; C. Hemoglobin <90 g/L (<9 g/dL); D. If there is no clear liver metastasis, the upper limit (ULN) of alanine aminotransferase > is 2.5 times normal; If there is liver metastasis, alanine aminotransferase > 5×ULN; E. If there is no definite liver metastasis, aspartate aminotransferase > 2.5×ULN; If there is liver metastasis, aspartic acid aminotransferase > 5×ULN; F. If there is no definite liver metastasis, total bilirubin > 1.5×ULN; Gilbert syndrome (unbound hyperbilirubinemia) or liver metastasis, total bilirubin > 3×ULN; G. Creatinine > 1.5×ULN and creatinine clearance <50 mL/min (calculated by Cockcroft - Gault formula); Confirmation of creatinine clearance is required only if creatinine > 1.5×ULN.
- 10. Women during lactation or in the study who had positive blood or urine pregnancy test results within 3 days before the first administration of treatment.
- 11. A history of hypersensitivity to any active or inactive component of amitinib or to drugs chemically similar to or similar to amitinib.
- 12. A history of hypersensitivity to any active or inactive component of pyrrolitinib or to drugs chemically similar to or similar to pyrrolitinib.
- 13. Any serious or uncontrolled ocular lesions that may, in the judgment of the physician, increase the patient's safety risk.
- 14. Patients identified by the investigator as likely to have poor compliance with study procedures and requirements.
- 15. Patients identified by the investigator as having any condition that jeopardizes patient safety or interferes with study evaluation.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Sun Yat-sen University Cancer Center
Guangzhou, Guangdong
Feng Wen Fang, MD., +86-15322302066
About this study
Official title: To Evaluate the Safety and Efficacy of Almonertinib Combined With Pyrotinib in the Treatment of Advanced NSCLC Patients With HER-2 Amplification/Mutation After EGFR-TKI Resistance: a Multicenter, Open-label Trial
This is a multicenter, open, phase II clinical trial to evaluate the safety and efficacy of almonertinib combined with pyrrolitinib in locally advanced or metastatic NSCLC patients with her-2 variants detected after first-line EGFR-TKI treatment resistance. Patients with first-line EGFR-TKI resistance showed HER-2 variation (including mutation and amplification) in tissue or blood tests, and the treatment regimen of metinil combined with pyrrolitinib was performed to evaluate the safety and efficacy of the treatment regimen. To determine the optimal dose of pyrrolitinib, three dose groups of 240mg, 320mg, and 400mg were set, and the "3+3" study design principle was adopted. About 27-36 people will be included in the study (depending on the progress of the study)
- Conditions
- Safety
- Being tested
- Almonertinib combine with Pyrrolitinib
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Almonertinib combine with PyrrolitinibDrug
110mg,qd Almonertinib+（240mg/320mg/400mg）,qd Pyrrolitinib
| Study group | Role | What they receive |
|---|---|---|
| almonertinib | Experimental | Not described Receives: Drug: Almonertinib combine with Pyrrolitinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Security of Almonertinib combined with Pyrotinib in the treatment of advanced NSCLC patients with HER-2 amplification/mutation after EGFR-TKI resistance
Measured: 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Mar 2021
- Study start31 Dec 2020
- Primary completionDec 2023 (estimated)
- Study completionDec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SafetyStudies of the same condition, open and under way.
- More trials run by Sun Yat-sen UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 36 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sun Yat-sen University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Li Zhang, MD, Sun Yat-sen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04785729
- Sponsor's protocol ID
- YX-L-202009/MA-NSCLC-II-014
- Acronym
- APPEAR
- Status last verified
- Mar 2021
- First submitted
- 25 Jan 2021
- Last updated
- 8 Mar 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- To Evaluate the Safety and Efficacy of Almonertinib Combined With Pyrotinib in the Treatment of Advanced NSCLC Patients With HER-2 Amplification/Mutation After EGFR-TKI Resistance: a Multicenter, Open-label Trial
- ClinicalTrials.gov ID
- NCT04785729
- Acronym / sponsor ID
- APPEAR / YX-L-202009/MA-NSCLC-II-014
- Conditions
- Safety
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 36 participants (estimated)
- Lead sponsor
- Sun Yat-sen UniversityUniversity, hospital or other
- Study start
- 31 Dec 2020 (actual)
- Primary completion
- Dec 2023 (estimated)
- Study completion
- Dec 2023 (estimated)
- First posted
- 8 Mar 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a multicenter, open, phase II clinical trial to evaluate the safety and efficacy of almonertinib combined with pyrrolitinib in locally advanced or metastatic NSCLC patients with her-2 variants detected after first-line EGFR-TKI treatment resistance. Patients with first-line EGFR-TKI resistance showed HER-2 variation (including mutation and amplification) in tissue or blood tests, and the treatment regimen of metinil combined with pyrrolitinib was performed to evaluate the safety and efficacy of the treatment regimen. To determine the optimal dose of pyrrolitinib, three dose groups of 240mg, 320mg, and 400mg were set, and the "3+3" study design principle was adopted. About 27-36 people will be included in the study (depending on the progress of the study)
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| almonertinib | Experimental | Drug: Almonertinib combine with Pyrrolitinib |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 1. 18 ≤ age ≤75, regardless of gender. 2. Non-squamous NSCLC (including stage IIIB-IV patients who relapsed after previous surgical treatment or were newly diagnosed). According to AJCC edition 8 lung cancer Staging Criteria) 3. Previous treatment with EGFR-TKI (not limited to algebra) and radiographic disease progression were permitted with less than or equal to first-line chemotherapy.
- 4. Before inclusion in this study (after the last treatment), tumor tissues or blood samples were detected with EGFR-sensitive 19 exon deletion or L858R mutation (with or without T790M), and her-2 mutation (including sensitive mutation or amplification, in which amplification should be confirmed by FISH).
- 5. The Eastern Tumor Tissue Cooperative Group (ECOG) physical status score was 0 or 1 and did not deteriorate in the previous 2 weeks, with a minimum expected survival of 12 weeks.
- 6. The patient had at least one tumor lesion that had not received previous local treatment such as irradiation, nor had he received biopsy during the screening period, and it could be accurately measured at baseline, with the longest diameter ≥ 10mm at baseline (short diameter ≥ 15mm for lymph nodes). The measurement method chosen is suitable for accurate repeated measurements and can be computed tomography (CT) or magnetic resonance imaging (MRI). If there is only one measurable lesion and no previous local treatment such as irradiation, it may be accepted as the target lesion, and a baseline evaluation of the tumor lesion shall be conducted at least 14 days after the diagnostic biopsy.
- 7. For fertile women, appropriate contraception should be used and breastfeeding should not be performed for 3 months from screening to discontinuation of study treatment. A pregnancy test is negative before administration, or there is no proven risk of pregnancy if one of the following criteria is met: A. Postmenopause is defined as amenorrhea over the age of 50 and at least 12 months after cessation of all exogenous hormone replacement therapy.
Key exclusion criteria (15 listed)
- 1. Received any of the following treatments: A. Patients had undergone major surgery within 4 weeks before the first administration of the study drug; B. Received more than 30% of bone marrow irradiation or extensive radiotherapy within 4 weeks before the first administration of the drug; C. Within 7 days before the first administration of the study drug, CYP3A4 inhibitory agent, inducer or drug with narrow therapeutic window for CYP3A4 sensitive substrate was used.
- 2. Patients with other malignancies requiring standard treatment or major surgery within 2 years of the first administration of the treatment under study.
- 3. At the time of initiation of treatment, there was residual toxicity from previous treatment that was not alleviated, greater than CTCAE level 1, except for hair loss and level 2 neurotoxicity caused by previous chemotherapy.
- 4. Spinal cord compression or brain metastases, unless asymptomatic, stable, and not requiring steroid therapy at least 2 weeks prior to the first administration of the study treatment.
- 5. At the investigator's discretion, there were any serious or poorly controlled systemic diseases, such as poorly controlled hypertension, active bleeding constitutions, or active infections. There is no need to screen for chronic diseases.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Almonertinib combine with Pyrrolitinib110mg,qd Almonertinib+（240mg/320mg/400mg）,qd Pyrrolitinib | Drug | almonertinib |
Primary outcome
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time frame: 36 months
Security of Almonertinib combined with Pyrotinib in the treatment of advanced NSCLC patients with HER-2 amplification/mutation after EGFR-TKI resistance
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Mar 2021.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Almonertinib combine with Pyrrolitinib in people with Safety, run by Sun Yat-sen University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 8 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Feng Wen Fang, MD. (+86-15322302066, fangwf@sysucc.org.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 (time frame: 36 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Mar 2021.