Non-Small Cell Lung Cancer Stage IIIAPhase 2ANSWERNCT04455594
Almonertinib Vs. Erlotinib/Chemotherapy for Neo-adjuVant Treatment of Stage IIIA-N2 EGFR-mutated NSCLC
A Phase 2 study testing Almonertinib, Erlotinib and Cisplatin in people with Non-Small Cell Lung Cancer Stage IIIA, run by The First Affiliated Hospital of Guangzhou Medical University at 1 site in China.
Trial summary
This is a multicenter, randomized, controlled, phase II study assessing the efficacy and safety of Almonertinib compared Erlotinib or platinum doublet chemotherapy (carboplatin or cisplatin + pemetrexed) as neoadjuvant therapy to EGFRm+ IIIA-N2 NSCLC patients. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Non-Small Cell Lung Cancer Stage IIIA
- What is being tested?
- Almonertinib, Erlotinib and Cisplatin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 168 participants
- Where
- 1 siteChina
- Study dates
- Oct 2020to Oct 2025
- 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
- Male or female, age at least 18 years, no more than 75 years.
- Previously untreated, histologically documented NSCLC with completely or potentially resectable IIIA-N2 nonsquamous NSCLC(according to Version 8 of AJCC staging). N2 is defined as as radiologically and pathologically confirmed, nonbulky metastases to single-station mediastinal lymph nodes (lymph nodes < 2 cm in short axis) that are expected to be completely resectable.
- Tumor tissue samples or blood samples are confirmed as EGFR sensitive mutations by central laboratory tests (including Ex19del or L858R, both alone or with other EGFR mutations). If the tumor tissue is accessible, the tumor tissue is recommended to be submitted for examination. If tumor tissue is not accessible or patient cannot undergo tissue biopsy, blood sample is also allowed.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 with no deterioration over the previous 2 weeks and a minimum life expectancy of 12 weeks.
- At least 1 lesion that has not previously been irradiated, that has not been chosen for biopsy during the study screening period, and that can be accurately measured at Baseline as >= 10 mm in the longest diameter (except lymph nodes, which must have short axis >= 15mm) with computerized tomography (CT) or magnetic resonance imaging (MRI), whichever is suitable for accurately repeated measurements. If only one measurable lesion exists, it is acceptable to be used (as a target lesion) as long as it has not been previously irradiated and baseline tumour assessment scans are done at least 14days afar the screening biopsy is performed.
- Women of childbearing potential must use a contraception method during the study treatment and for at least 3 months after the treatment is completed; must have a negative pregnancy test prior to starting treatment or proved no risk of pregancy by meeting one of the following criteria:
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- Postmenopausal defined as age more than 50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments.
- Women under 50 years old would be considered postmenopausal if they have been amenorrheic for 12 months or more, following cessation of exogenous hormonal treatments, and with luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels in the postmenopausal range for the laboratory.
- Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy, but not by tubal ligation.
- Male patients should be willing to use barrier contraception (i.e., condoms) during the study treatment and for at least 3 months after the treatment is completed.
- Signed and dated informed consent form.
Who cannot join
- Treatment with any of the following:
- Prior surgical resection of lung cancer.
- Prior treatment with any EGFR TKI.
- Prior treatment with any chemotherapy for NSCLC
- Prior treatment with any radiotherapy for NSCLC
- Major surgery (excluding placement of vascular access) within 4 weeks of the first dose of study drug.
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- Medications that are predominantly CYP3A4 strong inhibitors or inducers or sensitive substrates of CYP3A4 with a narrow therapeutic range within 7 days of the first dose of study drug.
- Any concurrent and/or other active malignancy that has required treatment within 2 years of first dose of study drug.
- Any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 at the time of starting study treatment, with the exception of alopecia and Grade 2 prior platinum-therapy related neuropathy.
- Patients with malignant pleural effusion. [only exception: pleural effusion on CT scan (not visible on CXR) or considered too small and pericardial effusion]
- Patients who received yellow-fever vaccine or other attenuated live vaccine during pemetrexed treatment.
- Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension or active bleeding diatheses, which, in the Investigator's opinion, makes it undesirable for the patient to participate in the trial OR which would jeopardize compliance with the protocol such as active infection. Screening for chronic conditions is not required.
- Refractory nausea, vomiting, or chronic gastrointestinal diseases, inability to swallow the study drug, or previous significant bowel resection that would preclude adequate absorption of Almonertinib.
- Any of the following cardiac criteria:
- Mean resting corrected QT interval (QTc) > 470 ms obtained from 3 electrocardiograms (ECGs), using the screening clinic's ECG machine and Fridericia's formula for QT interval correction (QTcF).
- Any clinically important abnormalities in rhythm, conduction, or morphology of the resting ECG (e.g., complete left bundle branch block, third-degree heart block, second-degree heart block, PR interval > 250 ms).
- Any factors that increase the risk of QTc prolongation or risk of arrhythmic events, such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death under 40 years of age in first degree relatives or any concomitant medication known to prolong the QT interval.
- Left ventricular ejection fraction (LVEF) <= 40%.
- History of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis that required steroid treatment, or any evidence of clinically active interstitial lung disease.
- Inadequate bone marrow reserve or organ function, as demonstrated by any of the following laboratory values:
- Absolute neutrophil count (ANC) < 1.5 x 10^9 / L;
- Platelet count <100 x 10^9 / L;
- Hemoglobin < 90 g/L (<9 g/dL);
- Alanine aminotransferase > 2.5 x upper limit of normal (ULN).
- Aspartate aminotransferase (AST) > 2.5 x ULN.
- Total bilirubin (TBL) > 1.5 x ULN or > 3 x ULN in the presence of documented Gilbert's Syndrome (unconjugated hyperbilirubinemia).
- Creatinine > 1.5 x ULN concurrent with creatinine clearance < 50 mL/min (measured or calculated by the Cockcroft-Gault equation); confirmation of creatinine clearance is only required when creatinine is > 1.5 x ULN.
- Women at breastfeeding or have a negative serum or urine pregnancy test in the 3 days prior to the start of the treatment..
- History of hypersensitivity to any active or inactive ingredient of Almonertinib, or to drugs with a similar chemical structure or class to Almonertinib.
- History of hypersensitivity to any active or inactive ingredient of Erlotinib, or to drugs with a similar chemical structure or class to Erlotinib.
- With lactose in the tablets, patients with rare genetic disease like galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption should not use use erlotinib.
- Patients who are allergic to pemetrexed or any other component of the preparation, carboplatin or cisplatin.
- Patients with contraindications of pemetrexed and carboplatin or cisplatin.
- Any severe and uncontrolled ocular disease that may, in the ophthalmologist's opinion, present a specific risk to the patient's safety.
- Judgment by the Investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions, and requirements.
- Any disease or condition that, in the opinion of the Investigator, would compromise the safety of the patient or interfere with study assessments.
Trial locations and contacts
1 site in 1 country.
China1 site
The First Affiliated Hospital of Guangzhou Medical University
Guangzhou
Wenhua Liang, 13710249454, Liangwh1987@163.com
About this study
Official title: Almonertinib Vs. Erlotinib/Chemotherapy for Neo-adjuVant Treatment of Stage IIIA-N2 EGFR-mutated NSCLC: a Multicenter, Open-label, Phase II Randomized Controlled Trial
This is a multicenter, randomized, controlled, phase II study assessing the efficacy and safety of Almonertinib compared Erlotinib or platinum doublet chemotherapy (carboplatin or cisplatin + pemetrexed) as neoadjuvant therapy to EGFRm+ IIIA-N2 NSCLC patients.
- Conditions
- Non-Small Cell Lung Cancer Stage IIIA
- Being tested
- Almonertinib, Erlotinib, Cisplatin, Carboplatin, Pemetrexed
- Keywords
- resectable NSCLC, IIIA-N2 NSCLC
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AlmonertinibDrug
Also called HS-10296
Oral, 110mg QD
ErlotinibDrug
Oral, 150mg QD
CisplatinDrug
Cisplatin(75mg/m2) be administered with pemetrexed (500mg/m2) on Day 1 of every 3-week cycle for 3 cycles
CarboplatinDrug
Carboplatin (AUC=5) to be administered with pemetrexed (500mg/m2) on Day 1 of every 3-week cycle for 3 cycles
PemetrexedDrug
Pemetrexed (500mg/m2) to be administered with Cisplatin(75mg/m2) or Carboplatin (AUC=5) on Day 1 of every 3-week cycle for 3 cycles
| Study group | Role | What they receive |
|---|---|---|
| Almonertinib | Experimental | Almonertinib 110mg QD Receives: Drug: Almonertinib |
| Investigator-choice therapy (Erlotinib or Chemotherapy) | Active comparator | Erlotinib 150mg QD or Cisplatin(75mg/m2) or Carboplatin (AUC=5) to be administered with pemetrexed (500mg/m2) on Day 1 of every 3-week cycle for 3 cycles Receives: Drug: Erlotinib; Drug: Cisplatin; Drug: Carboplatin; Drug: Pemetrexed |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective response rate (ORR)
Objective Response Rate (ORR) is defined as participants who had complete response (CR) or partial response(PR) divided by the total number of patients.
Measured: From date of randomization to an average of 6 weeks after the first dose
Secondary outcomes (8)
Pathological complete response (pCR)
Defined as absence of any residual cancer cells in the surgical specimen assessed post-surgery
Measured: From date of randomization to an average of 12 weeks after the first dose
Major Pathological Response (MPR)
Defined as ≤10% residual cancer cells in the surgical specimen, as assessed per central pathology laboratory post-surgery
Measured: From date of randomization to an average of 12 weeks after the first dose
Disease free survival (DFS)
DFS is defined as the time from the date of surgery until the first date of disease recurrence (local or distant) or date of death due to any cause, whichever occurs first.
If there is residual disease after surgery (eg. positive margins), the DFS event is the date of surgery.
Measured: From date of randomization up to approximately 18 months after date of resection
Overall Survival (OS)
Patients will be followed up to approximately 5.5 years after they are randomized.
Measured: Up to approximately 5.5 years after the last patient is randomized
R0 resection rate
Measured: Up to 1 week after surgery
Downstaging rate
Measured using lymph node staging
Measured: From date of randomization to an average of 12 weeks after the first dose
Concordance of EGFRm status between plasma-derived ctDNA
Measured: Baseline, up to 1 week before surgery and up to 1 week after surgery
Incidence of Adverse Events (AEs)
According to CTCAE4.0
Measured: Up to 80 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jul 2020
- Study startOct 2020 (estimated)
- Primary completionJan 2023 (estimated)
- Study completionOct 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-Small Cell Lung Cancer Stage IIIAStudies of the same condition, open and under way.
- More trials run by The First Affiliated Hospital of Guangzhou Medical 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 168 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jianxing He, The First Affiliated Hospital of Guangzhou Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04455594
- Sponsor's protocol ID
- HS-LK-2020-005
- Acronym
- ANSWER
- Status last verified
- Jun 2020
- First submitted
- 19 Jun 2020
- Last updated
- 2 Jul 2020
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Almonertinib Vs. Erlotinib/Chemotherapy for Neo-adjuVant Treatment of Stage IIIA-N2 EGFR-mutated NSCLC: a Multicenter, Open-label, Phase II Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT04455594
- Acronym / sponsor ID
- ANSWER / HS-LK-2020-005
- Conditions
- Non-Small Cell Lung Cancer Stage IIIA
- Keywords
- resectable NSCLC, IIIA-N2 NSCLC
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 168 participants (estimated)
- Lead sponsor
- The First Affiliated Hospital of Guangzhou Medical UniversityUniversity, hospital or other
- Study start
- Oct 2020 (estimated)
- Primary completion
- Jan 2023 (estimated)
- Study completion
- Oct 2025 (estimated)
- First posted
- 2 Jul 2020 (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, randomized, controlled, phase II study assessing the efficacy and safety of Almonertinib compared Erlotinib or platinum doublet chemotherapy (carboplatin or cisplatin + pemetrexed) as neoadjuvant therapy to EGFRm+ IIIA-N2 NSCLC patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Almonertinib | Experimental | Drug: AlmonertinibAlmonertinib 110mg QD |
| Investigator-choice therapy (Erlotinib or Chemotherapy) | Active comparator | Drug: Erlotinib, Drug: Cisplatin, Drug: Carboplatin, Drug: PemetrexedErlotinib 150mg QD or Cisplatin(75mg/m2) or Carboplatin (AUC=5) to be administered with pemetrexed (500mg/m2) on Day 1 of every 3-week cycle for 3 cycles |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Male or female, age at least 18 years, no more than 75 years.
- Previously untreated, histologically documented NSCLC with completely or potentially resectable IIIA-N2 nonsquamous NSCLC(according to Version 8 of AJCC staging). N2 is defined as as radiologically and pathologically confirmed, nonbulky metastases to single-station mediastinal lymph nodes (lymph nodes < 2 cm in short axis) that are expected to be completely resectable.
- Tumor tissue samples or blood samples are confirmed as EGFR sensitive mutations by central laboratory tests (including Ex19del or L858R, both alone or with other EGFR mutations). If the tumor tissue is accessible, the tumor tissue is recommended to be submitted for examination. If tumor tissue is not accessible or patient cannot undergo tissue biopsy, blood sample is also allowed.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 with no deterioration over the previous 2 weeks and a minimum life expectancy of 12 weeks.
- At least 1 lesion that has not previously been irradiated, that has not been chosen for biopsy during the study screening period, and that can be accurately measured at Baseline as >= 10 mm in the longest diameter (except lymph nodes, which must have short axis >= 15mm) with computerized tomography (CT) or magnetic resonance imaging (MRI), whichever is suitable for accurately repeated measurements. If only one measurable lesion exists, it is acceptable to be used (as a target lesion) as long as it has not been previously irradiated and baseline tumour assessment scans are done at least 14days afar the screening biopsy is performed.
Key exclusion criteria (36 listed)
- Treatment with any of the following:
- Any concurrent and/or other active malignancy that has required treatment within 2 years of first dose of study drug.
- Any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 at the time of starting study treatment, with the exception of alopecia and Grade 2 prior platinum-therapy related neuropathy.
- Patients with malignant pleural effusion. [only exception: pleural effusion on CT scan (not visible on CXR) or considered too small and pericardial effusion]
- Patients who received yellow-fever vaccine or other attenuated live vaccine during pemetrexed treatment.
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 |
|---|---|---|
| AlmonertinibAlso: HS-10296Oral, 110mg QD | Drug | Almonertinib |
| ErlotinibOral, 150mg QD | Drug | Investigator-choice therapy (Erlotinib or Chemotherapy) |
| CisplatinCisplatin(75mg/m2) be administered with pemetrexed (500mg/m2) on Day 1 of every 3-week cycle for 3 cycles | Drug | Investigator-choice therapy (Erlotinib or Chemotherapy) |
| CarboplatinCarboplatin (AUC=5) to be administered with pemetrexed (500mg/m2) on Day 1 of every 3-week cycle for 3 cycles | Drug | Investigator-choice therapy (Erlotinib or Chemotherapy) |
| PemetrexedPemetrexed (500mg/m2) to be administered with Cisplatin(75mg/m2) or Carboplatin (AUC=5) on Day 1 of every 3-week cycle for 3 cycles | Drug | Investigator-choice therapy (Erlotinib or Chemotherapy) |
Primary outcome
Objective response rate (ORR)
Time frame: From date of randomization to an average of 6 weeks after the first dose
Objective Response Rate (ORR) is defined as participants who had complete response (CR) or partial response(PR) divided by the total number of patients.
8 secondary outcomes
Pathological complete response (pCR)
Time frame: From date of randomization to an average of 12 weeks after the first dose
Major Pathological Response (MPR)
Time frame: From date of randomization to an average of 12 weeks after the first dose
Disease free survival (DFS)
Time frame: From date of randomization up to approximately 18 months after date of resection
Overall Survival (OS)
Time frame: Up to approximately 5.5 years after the last patient is randomized
R0 resection rate
Time frame: Up to 1 week after surgery
Downstaging rate
Time frame: From date of randomization to an average of 12 weeks after the first dose
Concordance of EGFRm status between plasma-derived ctDNA
Time frame: Baseline, up to 1 week before surgery and up to 1 week after surgery
Incidence of Adverse Events (AEs)
Time frame: Up to 80 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2020.
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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, Erlotinib and Cisplatin in people with Non-Small Cell Lung Cancer Stage IIIA, run by The First Affiliated Hospital of Guangzhou Medical 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 11 inclusion and 36 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 2 Jul 2020. 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 Wenhua Liang (13710249454, Liangwh1987@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective response rate (ORR) (time frame: From date of randomization to an average of 6 weeks after the first dose). 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 2 Jul 2020.