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

NCT ID: NCT05271916

Last Updated: 2023-04-19

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 140 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-10-13
• Study Completion Date: 2027-05-01

Brief Summary

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.

Conditions

Non-Small Cell Lung Cancer (NSCLC)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Combined treatment group

Dacomitinib+Anlotinib: Patients will be treated with combined Dacomitinib and Anlotinib.

Group Type: EXPERIMENTAL

Dacomitinib+Anlotinib

Intervention Type: DRUG

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.

Dacomitinib monotherapy group

Dacomitinib: Patients will be treated with Dacomitinib.

Group Type: ACTIVE_COMPARATOR

Dacomitinib

Intervention Type: DRUG

Dacomitinib orally on a continuous daily basis at a starting dose of 45 mg once a day until progressive disease.

Interventions

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.

Intervention Type: DRUG

Dacomitinib

Dacomitinib orally on a continuous daily basis at a starting dose of 45 mg once a day until progressive disease.

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shanghai Chest Hospital

OTHER

Sponsor Role: lead

Responsible Party

Baohui Han

Director of Respiratory Department

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Shanghai Chest Hospital

Shanghai, Shanghai Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Bo Zhang, MD

Role: CONTACT

zb1063253078@163.com

15800386291

Facility Contacts

Baohui Han, M.D

Role: primary

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Other Identifiers

IS22001

Identifier Type: -

Identifier Source: org_study_id