Almonertinib as First-line Treatment in Patients With EGFR+ Positive Pulmonary Adenosquamous Carcinoma or Combined Adenocarcinoma and Squamous Cell Carcinoma

NCT04354961 | Unknown Phase 2

• 1 other identifier: HS-LK-2020-003
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 18

Brief Summary

This is a prospective, multi-center, single-arm clinical trial.

Conditions

Pulmonary Adenosquamous Carcinoma

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  To assess the efficacy of Almonertinib as first line therapy to EGFRm+, locally advanced or metastatic Pulmonary Adenosquamous Carcinoma patients by assessment of progression free survival (PFS) using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).

  From baseline, then every 6 weeks, until disease progression or discontinuation from study. From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months.

Secondary Outcomes (9)

• Assess the anti-tumor activity: OS

  Start of study drug to Survival Endpoint through study completion, an average of 4 years.

• Assess the anti-tumor activity: ORR

  From baseline, then every 6 weeks, until disease progression or discontinuation from study. ORR is defined as the percentage of patients who have at least 1 response of CR or PR prior to any evidence of progression assessed up to 24 months.

• Assess the anti-tumor activity: DCR

  From baseline, then every 6 weeks, until disease progression or discontinuation from study. The DCR is defined as the proportion of patients with a best overall response of CR, PR, or SD assessed up to 24 months.

• Assess the anti-tumor activity: DoR

  DoR is defined as the time from the date of first documented response until the date of documented progression or death in the absence of disease progression assessed up to 24 months.

• Assess the safety of Almonertinib : Number of AEs/SAEs

  Continuously throughout the study until 28 days after Termination of the treatment

Study Arms (1)

Almonertinib 110mg PO once daily

EXPERIMENTAL

Drug: Almonertinib

Interventions

Almonertinib DRUG

Almonertinib 110mg PO once daily. A cycle of treatment is defined as 21 days of once daily treatment. Number of Cycles: as long as patients are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria.

Also known as: Investigational Product

Almonertinib 110mg PO once daily

Eligibility Criteria

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

You may qualify if:

• Provision of informed consent prior to any study specific procedures, sampling and analyses.
• Male or female, age at least 18 years.
• Pathologically confirmed locally advanced or metastatic pulmonary adenosquamous carcinoma. Patients must be treatment-naïve for locally advanced or metastatic pulmonary adenosquamous carcinoma. provided all other entry criteria are satisfied.
• Prior adjuvant and neo-adjuvant therapy is permitted (chemotherapy, radiotherapy, investigational agents) if 6 months or more have passed since completion of therapy.
• The tumour harbours EGFR genes mutations assessed by central testing using tissue, blood, pleural effusion, peritoneal effusion, and cerebrospinal fluid samples..
• A WHO performance status equal to 0-2 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.
• Females should be using adequate contraceptive measures throughout the study; should not be breastfeeding at the time of screening, during the study and until 3 months after completion of the study; and must have a negative pregnancy test prior to start of dosing if of childbearing potential or must have evidence of non-childbearing potential by fulfilling 1 of the following criteria at Screening:
• 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).

You may not qualify if:

• Treatment with any of the following:
• Prior treatment with an EGFR TKI.
• Major surgery (excluding placement of vascular access) within 4 weeks of the first dose of study drug.
• Radiotherapy with a limited field of radiation for palliation within 4 week of the first dose of study drug, with the exception of patients receiving radiation to \> 30% of the bone marrow or with a wide field of radiation 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.
• Patients with other malignancies requiring standard treatment or major surgery within 2 years after the first dose of study treatment, except basal cell carcinoma and carcinoma in situ.
• 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.
• 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 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%.
• Past medical 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.

Sponsors & Collaborators

• Fujian Cancer Hospital: lead
• Jiangsu Hansoh Pharmaceutical Co., Ltd.: collaborator

Study Sites (18)

Beijing Cancer Hospital

Beijing, China

NOT YET RECRUITING

Beijing Chest Hospital, Capital Medical University

Beijing, China

RECRUITING

Cancer Hospital Chinese Academy of Medical Sciences

Beijing, China

NOT YET RECRUITING

Hunan Cancer Hospital

Changsha, China

NOT YET RECRUITING

The Second Xiangya Hospital of Central South University

Changsha, China

NOT YET RECRUITING

Xinqiao Hospital, Army Medical University

Chongqing, China

NOT YET RECRUITING

Fujian Cancer Hospital

Fuzhou, China

RECRUITING

Fujian Provincial Hospital

Fuzhou, China

NOT YET RECRUITING

Sir Run Run Shaw Hospital

Hangzhou, China

NOT YET RECRUITING

The second Affiliated Hospital of Kunming Medical University

Kunming, China

NOT YET RECRUITING

The second Affiliated Hospital of Nanchang University

Nanchang, China

RECRUITING

Jiangsu Province Hospital

Nanjing, China

NOT YET RECRUITING

Shanghai Chest Hospital

Shanghai, China

RECRUITING

Tianjin Medical University Cancer Institute & Hospital

Tianjin, China

RECRUITING

Tongji Hospital of Tongji Medical College,Huazhong University of Science and Technology

Wuhan, China

RECRUITING

Air Force Medical University of PLA (the Fourth Military Medical University)

Xi'an, China

NOT YET RECRUITING

Henan Cancer Hospital

Zhengzhou, China

NOT YET RECRUITING

Henan Provincial People's Hospital

Zhengzhou, China

NOT YET RECRUITING

MeSH Terms

Interventions

aumolertinib

Central Study Contacts

Gen Lin

CONTACT

86+0591-62002057; lingen197505@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 17, 2020
• First Posted: April 21, 2020
• Study Start: May 7, 2021
• Primary Completion: December 31, 2023
• Study Completion: June 30, 2025
• Last Updated: November 8, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (18)