Almonertinib Vs. Erlotinib/Chemotherapy for Neo-adjuVant Treatment of Stage IIIA-N2 EGFR-mutated NSCLC

NCT04455594 | Unknown Phase 2

• 1 other identifier: HS-LK-2020-005
• Study Type: interventional
• Target: 168
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Non-Small Cell Lung Cancer Stage IIIA

Keywords

resectable NSCLC, IIIA-N2 NSCLC

Outcome Measures

Primary Outcomes (1)

• 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.

  From date of randomization to an average of 6 weeks after the first dose

Secondary Outcomes (8)

• Pathological complete response (pCR)

  From date of randomization to an average of 12 weeks after the first dose

• Major Pathological Response (MPR)

  From date of randomization to an average of 12 weeks after the first dose

• Disease free survival (DFS)

  From date of randomization up to approximately 18 months after date of resection

• Overall Survival (OS)

  Up to approximately 5.5 years after the last patient is randomized

• R0 resection rate

  Up to 1 week after surgery

Study Arms (2)

Almonertinib

EXPERIMENTAL

Almonertinib 110mg QD

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

Drug: Erlotinib; Drug: Cisplatin; Drug: Carboplatin; Drug: Pemetrexed

Interventions

Almonertinib DRUG

Oral, 110mg QD

Also known as: HS-10296

Almonertinib

Erlotinib DRUG

Oral, 150mg QD

Investigator-choice therapy (Erlotinib or Chemotherapy)

Cisplatin DRUG

Cisplatin(75mg/m2) be administered with pemetrexed (500mg/m2) on Day 1 of every 3-week cycle for 3 cycles

Investigator-choice therapy (Erlotinib or Chemotherapy)

Carboplatin DRUG

Carboplatin (AUC=5) to be administered with pemetrexed (500mg/m2) on Day 1 of every 3-week cycle for 3 cycles

Investigator-choice therapy (Erlotinib or Chemotherapy)

Pemetrexed DRUG

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

Investigator-choice therapy (Erlotinib or Chemotherapy)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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.

You may not qualify if:

• 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.
• 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).

Sponsors & Collaborators

• The First Affiliated Hospital of Guangzhou Medical University: lead

Study Sites (1)

The First Affiliated Hospital of Guangzhou Medical University

Guangzhou, China

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

aumolertinib; Erlotinib Hydrochloride; Cisplatin; Carboplatin; Pemetrexed

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)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Organic Chemicals; Guanine; Hypoxanthines; Purinones; Purines; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic

Central Study Contacts

Wenhua Liang

CONTACT

13710249454; Liangwh1987@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Surgeon

Study Record Dates

• First Submitted: June 19, 2020
• First Posted: July 2, 2020
• Study Start: October 1, 2020
• Primary Completion: January 1, 2023
• Study Completion: October 1, 2025
• Last Updated: July 2, 2020

Record last verified: 2020-06

Locations

CN (1)