Almonertinib With Bevacizumab for EGFR-Mutant NSCLC Patients With Leptomeningeal Metastasis (ATTRACT)

June 26, 2021 updated by: Second Affiliated Hospital of Nanchang University

Almonertinib Combined With Bevacizumab for EGFR-Mutant NSCLC Patients With Leptomeningeal Metastasis: A Prospective, Open-label, Multi-center, Single-arm Study

A prospective, open-label, multi-center, single-arm study of Almonertinib combined With Bevacizumab for EGFR-mutant NSCLC patients with leptomeningeal metastasis.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

This is a prospective, open-label, multi-center, single-arm study to evaluate the efficacy and safety of Almonertinib combined with Bevacizumab for EGFR-mutant NSCLC patients with leptomeningeal metastasis. ALL patients were treated with Almonertinib 110mg oral daily and Bevacizumab 15mg/kg intravenous every 3 weeks. Study therapy continued until disease progression, unacceptable adverse event, or withdrawal of consent.

Study Type

Interventional

Enrollment (Anticipated)

69

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Jiangxi
      • Nanchang, Jiangxi, China, 330006
        • The Second Afiliated Hospital of Nanchang University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Male or female, age in 18-75 years.
  2. The Eastern Cooperative Oncology Group (ECOG) physical status score is 0-2 and has not deteriorated in the previous 2 weeks, with a minimum expected survival of 12 weeks.
  3. Histologically confirmed patients with NSCLC leptomeningeal metastasis by positive cerebrospinal fluid cytological examination.
  4. Tumor tissue samples or blood are confirmed to be EGFR sensitive mutations (including exon 19 deletion or L858R).
  5. There must be at least one measurable extracranial lesion that has not been locally treated at the time of enrollment.
  6. 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: a) Postmenopausal defined as age more than 50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments. b) 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. c) Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy, but not by tubal ligation.
  7. Male patients should be willing to use barrier contraception (i.e., condoms).
  8. For inclusion in study, patient must provide a written informed consent.

Exclusion Criteria:

  1. Treatment with any of the following: a) Prior treatment with systemic anti-cancer therapy for locally advancer or metastatic NSCLC including chemotherapy, biologic therapy, immunotherapy, or any investigational drug. b) Prior treatment with an EGFR TKI. c) Major surgery (excluding placement of vascular access) within 4 weeks of the first dose of study drug. d) 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. e) 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.
  2. Patients with other malignancies, except basal cell carcinoma and carcinoma in situ.
  3. 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.
  4. 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..
  5. 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.
  6. Any of the following cardiac criteria: a) 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). b) 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). c) 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. d) Left ventricular ejection fraction (LVEF)< 50%.
  7. Inadequate bone marrow reserve or organ function, as demonstrated by any of the following laboratory values: a) Absolute neutrophil count (ANC) <1.5×10^9 / L. b) Platelet count <100×10^9 / L. c) Hemoglobin <90 g/L (<9 g/dL). d) Alanine aminotransferase > 2.5 × upper limit of normal (ULN) if no demonstrable liver metastases or > 5 × ULN in the presence of liver metastases. e) Aspartate aminotransferase (AST) > 2.5 × ULN if no demonstrable liver metastases or > 5 × ULN in the presence of liver metastases. f) Total bilirubin (TBL) > 1.5 × ULN if no liver metastases or > 3 × ULN in the presence of documented Gilbert's Syndrome (unconjugated hyperbilirubinemia) or liver metastases. g) Creatinine > 1.5 × 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 × ULN. h) ALB <28 g/L.
  8. 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.
  9. Women who are breastfeeding or have a positive urine or serum pregnancy test at the Screening Visit.
  10. History of hypersensitivity to any active or inactive ingredient of Almonertinib, or to drugs with a similar chemical structure or class to Almonertinib.
  11. 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.
  12. Any severe and uncontrolled ocular disease that may, in the ophthalmologist's opinion, present a specific risk to the patient's safety.
  13. Any disease or condition that, in the opinion of the Investigator, would compromise the safety of the patient or interfere with study assessments.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Almonertinib With Bevacizumab
Almonertinib 110 mg oral once daily with Bevacizumab 15 mg/kg intravenous on Day 1 of 21 day cycles (every 3 weeks)
Drug: Almonertinib
110 mg oral once daily
Drug: Bevacizumab
15 mg/kg intravenous on Day 1 of 21 day cycles (every 3 weeks)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival (OS)
Time Frame: From date of enrollment until the date of death, up to 2 years
OS is the time from the date of enrollment until death due to any cause
From date of enrollment until the date of death, up to 2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to Symptom Resolution
Time Frame: From baseline, then every 3 weeks, up to 2 years
Time to symptom resolution is the time from first drug dosage date (C1D1) until the date of symptom resolution
From baseline, then every 3 weeks, up to 2 years
Progression Free Survival (PFS)
Time Frame: From baseline, then every 6 weeks, up to 2 years
PFS is the time from date of enrollment until the date of PD (by investigator assessment) or death
From baseline, then every 6 weeks, up to 2 years
Objective Response Rate (ORR)
Time Frame: From baseline, then every 6 weeks, up to 2 years
ORR is the proportion of patients with a best overall response of complete response or partial response (CR+PR)
From baseline, then every 6 weeks, up to 2 years
Disease Control Rate (DCR)
Time Frame: From baseline, then every 6 weeks, up to 2 years
DCR is the proportion of patients with a best overall response of complete response, partial response or stable disease(CR+PR+SD)
From baseline, then every 6 weeks, up to 2 years
Duration of Response (DoR)
Time Frame: From baseline, then every 6 weeks, up to 2 years
DoR is the time from date of first documented response until the date of PD (by investigator assessment) or death
From baseline, then every 6 weeks, up to 2 years
Intracranial Progression Free Survival (iPFS)
Time Frame: From baseline, then every 6 weeks, up to 2 years
Intracranial progression-free survival
From baseline, then every 6 weeks, up to 2 years
Intracranial Objective Response Rate (iORR)
Time Frame: From baseline, then every 6 weeks, up to 2 years
Intracranial objective response rate
From baseline, then every 6 weeks, up to 2 years
Intracranial Disease Control Rate (iDCR)
Time Frame: From baseline, then every 6 weeks, up to 2 years
Intracranial disease control rate
From baseline, then every 6 weeks, up to 2 years
Intracranial Duration of Response (iDoR)
Time Frame: From baseline, then every 6 weeks, up to 2 years
Intracranial duration of response
From baseline, then every 6 weeks, up to 2 years
Extracranial Progression Free Survival (ePFS)
Time Frame: From baseline, then every 6 weeks, up to 2 years
Extracranial progression-free survival
From baseline, then every 6 weeks, up to 2 years
Extracranial Objective Response Rate (eORR)
Time Frame: From baseline, then every 6 weeks, up to 2 years
Extracranial objective response rate
From baseline, then every 6 weeks, up to 2 years
Extracranial Disease Control Rate (eDCR)
Time Frame: From baseline, then every 6 weeks, up to 2 years
Extracranial disease control rate
From baseline, then every 6 weeks, up to 2 years
Extracranial Duration of Response (eDoR)
Time Frame: From baseline, then every 6 weeks, up to 2 years
Extracranial duration of response
From baseline, then every 6 weeks, up to 2 years
Assess the safety of Almonertinib Combined With Bevacizumab
Time Frame: From baseline, then every 3 weeks, up to 2 years
Number of adverse events (AEs)/serious adverse events (SAEs)
From baseline, then every 3 weeks, up to 2 years

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Evaluate the correlation between the results of CSF genetic testing and drug resistance mechanisms
Time Frame: CSF samples will be collected on Cycle 1 Day 1, Cycle 2 Day 1 and within one week after disease progression (each cycle is 21 days)
Evaluate the correlation between the results of CSF genetic testing and drug resistance mechanisms
CSF samples will be collected on Cycle 1 Day 1, Cycle 2 Day 1 and within one week after disease progression (each cycle is 21 days)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Second Affiliated Hospital of Nanchang University

Collaborators

Jiangsu Hansoh Pharmaceutical Co., Ltd.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

July 1, 2021

Primary Completion (Anticipated)

March 1, 2024

Study Completion (Anticipated)

March 1, 2025

Study Registration Dates

First Submitted

May 26, 2021

First Submitted That Met QC Criteria

June 26, 2021

First Posted (Actual)

June 29, 2021

Study Record Updates

Last Update Posted (Actual)

June 29, 2021

Last Update Submitted That Met QC Criteria

June 26, 2021

Last Verified

May 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HSM-10296-A016

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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