Almonertinib/Pemetrexed/Carboplatin in EGFR T790M+ Advanced Lung Cancer (APPEAL)

Almonertinib Plus Pemetrexed and Carboplatin Versus Almonertinib Alone in Advanced NSCLC With EGFR T790M After First- or Second-generation TKIs Therapy: a Randomized, Controlled, Open-label, Phase 2 Study

Almonertinib Plus Pemetrexed and Carboplatin Versus Almonertinib Alone in Advanced NSCLC With EGFR T790M After First- or Second-generation TKIs Therapy: a Randomized, Controlled, Open-label, Phase 2 Study

Study Overview

• Status: Unknown
• Conditions: Lung Cancer, Non-small Cell; EGFR Gene Mutation; EGFR T790M
• Intervention / Treatment: Drug: Almonertinib; Drug: Pemetrexed; Drug: Carboplatin

• Study Type: Interventional
• Enrollment (Anticipated): 226
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Cancer hospital Fudan University

Participation Criteria

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. Between 18 and 75 years old (including 18 and 75 years old);
2. Histologically or cytologically confirmed locally advanced or metastatic (STAGE IIIB-IV) NSCLC does not accept simple sputum smear-based diagnosis;
3. Previous genetic tests confirmed egFR-sensitive mutations, and received one or two generations of EGFR TKI treatment. After drug resistance, it was confirmed to be positive for EGFR T790M mutation by biopsy or free DNA test.
4. The patient has at least one tumor lesion that has not received local treatment such as radiation or biopsy in the screening stage, and can be accurately measured at baseline, with the longest diameter ≥ 10mm at baseline (short diameter ≥ 15mm if lymph nodes are involved).The measurement method chosen is suitable for accurate repeated measurements and can be computed tomography (CT) or magnetic resonance imaging (MRI).If there is only one measurable lesion and no previous local treatment such as irradiation, it can be accepted as the target lesion for baseline evaluation of tumor lesions after at least 14 days of diagnostic biopsy.
5. Life expectancy is at least 3 months;
6. ECOG score: 0-1, with no significant clinical deterioration in the past 2 weeks;
7. The main organs function normally, that is, they meet the following standards:

blood routine examination standards must be in accordance with no blood transfusion and adjuvant therapies (14 days) : A. Hemoglobin (HB) ≥90 g/L; B. Absolute value of neutrophils (ANC) ≥1.5×109/L; C. Platelet (PLT) ≥100×109/L; D. Total bilirubin (TBIL) <1.5 times the upper limit of normal value (ULN); E. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <2.5×ULN, if accompanied by liver metastasis, ALT and AST< 5×ULN; F. Serum Cr<1.25×ULN or endogenous creatinine clearance rate (CCr) > 45 ml/min (Cockcroft-Gault formula);

Exclusion Criteria:

1. Patients who have received three generations of EGFR-TKI treatment;
2. Patients with mixed small cell lung cancer components;
3. Patients with advanced or metastatic disease who have received palliative chemotherapy, or patients with tumor recurrence and metastasis within 6 months after radical surgery with adjuvant chemotherapy;
4. Patients with symptomatic brain metastasis, meningeal metastasis or spinal cord compression;
5. Patients with previous diagnosis of interstitial pneumonia;
6. Uncontrolled hypertension (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg, despite the best medication);
7. with severe cardiovascular disease: Ⅱ magnitude of myocardial ischemia and myocardial infarction, poor control of cardiac arrhythmias (including QTc interphase male 450, female 470 ms or ms or higher);According to NYHA standard, Ⅲ ~ Ⅳ cardiac insufficiency, or heart colour to exceed revealed left ventricular ejection fraction (LVEF) < 50%;
8. abnormal coagulation function (INR >1.5 or prothrombin time (PT) > ULN+4 seconds or APTT > 1.5uln), bleeding tendency or receiving thrombolytic or anticoagulant therapy; Note: Under the condition that the international standard ratio of prothrombin time (INR) ≤1.5, low-dose heparin (daily dosage for adults ranges from 66,000 to 12,000 U) or low-dose aspirin (daily dosage ≤100 mg) is allowed for preventive purposes.
9. Peripheral neuropathy ≥CTCAE 2 is present, except for trauma;
10. Respiratory syndrome (≥CTCAE level 2 dyspnea), uncontrolled serous cavity effusion (including pleural effusion, ascites and pericardial effusion);
11. A wound or fracture that has not been healed for a long time;
12. Severe infections requiring systemic antibiotics;
13. Decompensated diabetes mellitus or other contraindications of high-dose glucocorticoid therapy;
14. Active hepatitis C and/or hepatitis B infection (hepatitis B: HBsAg positive with HBV DNA≥500IU/mL;Hepatitis C: HCV RNA positive);
15. Factors that significantly affect oral drug absorption, such as inability to swallow, chronic diarrhea, and intestinal obstruction;
16. Had major surgery or severe traumatic injury, fracture or ulcer within the first 4 weeks;
17. Any contraindications for platinum (carboplatin) and cytotoxic drug (Pemetrexed) treatment;
18. Other conditions deemed inappropriate by the researcher for inclusion in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Combinational therapy	Drug: Almonertinib; the standard therapy of single agent almonertinib; Drug: Pemetrexed; standard dose; Drug: Carboplatin; AUC=5
Active Comparator: Single TKI	Drug: Almonertinib; the standard therapy of single agent almonertinib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS	progression free survival	from the first cycle of treatment (day one) to two month after the last cycle (each cycle is 21 days)

Collaborators and Investigators

• Sponsor: Fudan University

Study record dates

Study Major Dates

• Study Start (Anticipated): October 9, 2020
• Primary Completion (Anticipated): December 31, 2021
• Study Completion (Anticipated): June 30, 2022

Study Registration Dates

• First Submitted: September 22, 2020
• First Submitted That Met QC Criteria: October 15, 2020
• First Posted (Actual): October 19, 2020

Study Record Updates

• Last Update Posted (Actual): October 19, 2020
• Last Update Submitted That Met QC Criteria: October 15, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: lung cancer; EGFR; Combination therapy; Almonertinib
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Folic Acid Antagonists; Carboplatin; Pemetrexed
• Other Study ID Numbers: ALMO-PEME-CAR-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: based on preliminary results

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No