First-line Treatment With Dacomitinib Plus Anlotinib for Patients With Advanced NSCLC With EGFR 21L858R Mutations

April 18, 2023 updated by: Baohui Han, Shanghai Chest Hospital

An Open Label, Multicenter, Phase I/IIB Study of Dacomitinib Plus Anlotinib for Advanced Non-Small Cell Lung Cancer (NSCLC) Harboring Epidermal Growth Factor Receptor (EGFR) 21-L858R Mutations.

This is a multicenter, open label, Phase I/IIB study investigating the efficacy and safety of treatment with dacomitinib plus anlotinib as first-line therapy for patients with advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) 21-L858R mutations. This study comprises two parts: 1. A dose escalation Phase I study to determine the recommended phase II dose. 2. a multi-center, open label, randomized controlled, Phase IIB study.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

140

Phase

  • Phase 2
  • Phase 1

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
    • Shanghai
      • Shanghai, Shanghai, China, 200000
        • Recruiting
        • Shanghai Chest Hospital
        • Contact:
          • Baohui Han, M.D

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

Description

Inclusion Criteria:

  1. ≥18 years of age and ≤75 years;
  2. Provision of a voluntarily given, personally signed and dated, written informed consent document;
  3. Histologically documented, unresectable, inoperable, locally advanced, recurrent or metastatic stage IIIB or IV non-small cell lung cancer (NSCLC);
  4. It is acceptable for subjects with the presence of EGFR activating mutation (exon 19 deletion and the L858R mutation in exon 21) to be included in this Phase I study; Only subjects with the L858R mutation in exon 21 to be included in this Phase IIb;
  5. At least one measurable disease by RECIST criteria version 1.1;
  6. Patients with controlled or stable brain metastases;
  7. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1, and life expectancy of at least 3 months;
  8. No prior treatment with systemic therapy for advanced NSCLC, including TCM treatments;
  9. Able to comply with required protocol procedures and able to receive oral medications;
  10. Adequate organ function, including:

(1) Adequate bone marrow function Hemoglobin≥90g/L, absolute neutrophil count (ANC) should be ≥ 1.5x109/L, platelets should be ≥ 80x109/L; (2) Adequate liver function Total bilirubin ≤ 1.5 x upper normal limit (ULN), Aspartate Aminotransferase (AST) (SGOT) ≤ 2.5 x ULN (≤ 5.0 x ULN if hepatic metastases), Alanine Aminotransferase (ALT) (SGPT) ≤ 2.5 x ULN (≤ 5.0 x ULN if hepatic metastases), Creatinine≤ 1.5 x upper normal limit (ULN), or ≥ 60 mL/min; (3) Cardiac function: LVEF≥50% assessed by Doppler ultrasound；

Exclusion Criteria:

  1. Small cell lung cancer (including mixed small cell and non-small cell lung cancer) and squamous cell carcinoma with cavitation;
  2. Patients with concurrent EGFR T790M mutation or unknown mutation status or other mutation types;
  3. Diagnosis of any other malignancy during the last 5 years, or with other malignancies at present;
  4. Patients with pre-existing meningeal metastases;
  5. Patients who have concurrent other malignant tumors;
  6. Any history of hemoptysis, hematochezia, bloody sputum;
  7. Tumor invasion or adjacent major vessels;
  8. Patients with uncontrolled or significant systematic disease, including: active infection, thyroid dysfunction, uncontrolled hypertension, unstable angina pectoris, congestive heart failure, or myocardial infarction within 6 months, or severe arrhythmia requiring medication;
  9. A history of other diseases, or metabolic dysfunction, or physical examination or laboratory results suggestive of a disease or condition that precludes the use of an investigational drug, or may affect the interpretation of the study results, or expose the patient to a high risk of treatment complications;
  10. Any astrointestinal disorders resulting in inability to take medications orally, or requiring intravenous (IV) nutrition, or previous surgery impair drug absorption;
  11. Pregnant or lactating females;
  12. Patients allergic to any pharmaceutical ingredient.

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: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Combined treatment group
Dacomitinib+Anlotinib: Patients will be treated with combined Dacomitinib and Anlotinib.
Drug: Dacomitinib+Anlotinib
The dose of each drug in the combination Decomitinib and Anlotinib will be escalated or de-escalated until the recommended phase II dose (RP2D) is reached. Patients will then be treated with RP2D orally once a day.
Active Comparator: Dacomitinib monotherapy group
Dacomitinib: Patients will be treated with Dacomitinib.
Drug: Dacomitinib
Dacomitinib orally on a continuous daily basis at a starting dose of 45 mg once a day until progressive disease.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall safety profile
Time Frame: Day 21 of Cycle 1, every 6 weeks until disease progression or death due to any cause, whichever occurred first (up to 22 months)
Overall safety profile of combined Dacomitinib plus Anlotinib in Escalation Phase, including adverse events (AE), as defined and graded by the National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE 4.03], and first cycle Dose Limiting Toxicities (DLTs).
Day 21 of Cycle 1, every 6 weeks until disease progression or death due to any cause, whichever occurred first (up to 22 months)
Progression Free Survival (PFS)
Time Frame: Day 21 of Cycle 1, every 6 weeks until disease progression or death due to any cause, whichever occurred first (up to 22 months)
Progression Free Survival (PFS) is defined as the time from start of treatment to the date of disease progression as defined by RECIST v1.1 per investigator review or death due to any cause, whichever occurred first.
Day 21 of Cycle 1, every 6 weeks until disease progression or death due to any cause, whichever occurred first (up to 22 months)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival (OS)
Time Frame: 48 months
Overall Survival is defined as the time from start of treatment to the date of death for any cause. In the absence of confirmation of death, survival time will be censored at the last date the subject is known to be alive.
48 months
Best Overall Response (BOR)
Time Frame: From baseline until disease progression, up to 48 months
Best overall response is best response from start of treatment until disease progression, and will calculated as the percentage of participants with an objective response (CR or PR) or stable disease, based on the RECIST v1.1, relative to the total number of participants enrolled in the cohort.
From baseline until disease progression, up to 48 months

Collaborators and Investigators

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

Sponsor

Shanghai Chest Hospital

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 (Actual)

October 13, 2022

Primary Completion (Anticipated)

January 1, 2025

Study Completion (Anticipated)

May 1, 2027

Study Registration Dates

First Submitted

February 28, 2022

First Submitted That Met QC Criteria

February 28, 2022

First Posted (Actual)

March 9, 2022

Study Record Updates

Last Update Posted (Actual)

April 19, 2023

Last Update Submitted That Met QC Criteria

April 18, 2023

Last Verified

April 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IS22001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

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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