Phase II Randomized Study on EGFR-TKI Sequencing with Dacomitinib and Osimertinib in Advanced EGFR-Mutant NSCLC
- Trial ID
- 2024-518223-29-00
- Protocol
- CAPLAND
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to assess the optimal sequencing of **epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs)** in patients with advanced or metastatic non-small-cell lung cancer (NSCLC) harboring EGFR mutations. This investigation aims to determine the efficacy of dacomitinib or osimertinib in patients with classical or uncommon activating EGFR mutations. The study includes patients with asymptomatic or controlled brain metastases, allowing for the evaluation of dacomitinib's efficacy in this specific population. Clinically, this is significant as it may inform treatment strategies to improve patient outcomes in this subset of NSCLC.
Secondary objectives include evaluating overall survival (OS) in patients treated with osimertinib first followed by dacomitinib, and vice versa. Progression-free survival (PFS) at the time of second-line therapy failure (PFS2) and PFS in patients treated with either osimertinib or dacomitinib first are also assessed. The study further examines response rate (RR) with each drug, as well as RR, PFS, and OS in patients with uncommon activating EGFR mutations. Additionally, the study evaluates intracranial RR and PFS, and the safety and incidence of adverse events (AEs) in patients treated with the sequence of osimertinib followed by dacomitinib, or the reverse.
Participants
The clinical trial involves participants diagnosed with **advanced or metastatic untreated EGFR mutation positive non-small cell lung cancer (NSCLC)**. The study population includes both male and female patients aged 18 years and older. Participants are required to have a histologically or cytologically confirmed diagnosis of stage IIIB/IV NSCLC with evidence of activating EGFR mutations. The trial does not include a vulnerable population. Participants must have a performance status of 0-1 according to the ECOG scale, indicating they are fully active or restricted in physically strenuous activity but ambulatory. The trial population was selected based on specific inclusion criteria, such as the absence of significant comorbidities that could interfere with trial participation, and the ability to comply with trial procedures. Lifestyle considerations, such as diet and physical activity, are not specified. The sponsor has not provided information regarding the total number of participants in the study.
Plans and Procedures
The clinical trial is a **randomized**, non-comparative, phase II study designed to evaluate the optimal sequence of epidermal growth factor receptor tyrosine kinase inhibitors (**EGFR-TKIs**) in patients with advanced or metastatic non-small-cell lung cancer (**NSCLC**) harboring EGFR mutations. The trial involves two investigational products: Vizimpro (dacomitinib) and TAGRISSO (osimertinib), both administered orally in the form of film-coated tablets. The primary objective is to assess overall survival (OS) in patients treated with either osimertinib or dacomitinib as the initial therapy. Secondary endpoints include progression-free survival (PFS) and response rate (RR) with different sequencing of the two drugs.
The trial is expected to last until July 31, 2025, with participant recruitment having commenced on June 16, 2020. Participants will be involved in the study for a maximum treatment period of 36 months. The study design includes an initial screening visit to confirm eligibility based on specific inclusion criteria, such as confirmed diagnosis of stage IIIB/IV NSCLC with activating EGFR mutations, and adequate organ function. Following the screening, participants will be randomized to receive either dacomitinib or osimertinib as the first-line treatment. Subsequent follow-up visits will be scheduled to monitor treatment efficacy and safety, with assessments conducted according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
The end-of-study visit will occur after the completion of the treatment period or upon early termination. Conditions that may lead to early termination from the study include significant adverse events, disease progression, or withdrawal of consent. Participants with asymptomatic or controlled brain metastases are eligible, provided they meet the stability criteria. The trial excludes individuals with previous EGFR-TKI therapy or significant comorbidities that could interfere with participation. The study aims to provide insights into the efficacy of dacomitinib and osimertinib in this patient population, including those with specific EGFR mutations and brain metastases.
Treatment
The clinical trial involves the administration of **Vizimpro** 15 mg film-coated tablets, which contain the active substance **dacomitinib**. Dacomitinib is a chemical compound classified under the ATC code L01EB07. The pharmaceutical form of the medication is a film-coated tablet, and it is administered orally. The maximum daily dose is 45 mg, with a total treatment period not exceeding 36 months. The medication is manufactured by Pfizer Europe MA EEIG and is not a pediatric formulation. Participants are required to adhere to the dosing schedule, and compliance will be monitored throughout the study.
Additionally, the trial includes the use of **TAGRISSO** 80 mg film-coated tablets, containing the active substance **osimertinib**. Osimertinib is also a chemical compound, categorized under the ATC code L01EB04. This medication is provided in the form of film-coated tablets and is administered orally. The maximum daily dose is 80 mg, with a treatment duration of up to 36 months. The product is manufactured by AstraZeneca AB and is not intended for pediatric use. Participant adherence to the dosing regimen will be closely monitored to ensure compliance.
Both medications are used in the context of a randomized, non-comparative, phase II study aimed at determining the optimal sequence of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in patients with advanced or metastatic non-small-cell lung cancer (NSCLC) harboring EGFR mutations. The study includes patients with classical or uncommon activating EGFR mutations and those with asymptomatic or controlled brain metastases, allowing for the evaluation of the efficacy of dacomitinib and osimertinib in these specific populations.
Efficacy
The efficacy of the clinical trial will be assessed through several primary and secondary endpoints. The primary endpoint is the overall survival (OS) in patients treated with either **osimertinib** or **dacomitinib** as the initial therapy. Secondary endpoints include OS in patients who receive osimertinib followed by dacomitinib and vice versa, progression-free survival (PFS) at the time of second-line therapy failure (PFS2), PFS in patients treated with either drug first, and the response rate (RR) with each drug. Additionally, the study will evaluate RR, PFS, and OS in patients undergoing the sequence of osimertinib followed by dacomitinib or the reverse.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Written informed consent; 2) Male or female patient aged =18 years; 3) Histologically/cytologically confirmed diagnosis of stage IIIB/IV NSCLC with evidence of activating EGFR mutations including exon 19 deletion, exon 21 L858R or other activating/sensitizing EGFR mutations such as exon 21 L861Q, exon 18 G719S, G719A, G719C, exon 20 S768I and V769L; co-occurrence of de novo T790M is not an exclusion criterion; EGFR status assessed in circulating DNA is allowed; 4) Patients eligible and candidate to receive osimertinib as first- or second-line treatment according to clinical practice and study design, as decided by Investigator regardless study participation; 5) Patients with brain metastases are allowed provided they are asymptomatic and stable (i.e. without evidence of progression by imaging for at least two weeks prior to the first dose of trial treatment and without deterioration of any neurologic symptoms); 6) No evidence of concomitant drivers including KRAS mutations, HER2 mutations, ALK or ROS1 rearrangements, MET mutations, BRAF mutations; 7) No previous EGFR-TKI therapy; Previous palliative radiotherapy or surgery allowed. Prior brain radiotherapy and Stereotactic Radiosurgery (SRS) are allowed. Previous neo/adjuvant chemotherapy is allowed as long as therapy was completed at least 6 months before diagnosis of advanced or metastatic NSCLC; 8) At least one radiological measurable disease according to RECIST criteria version 1.1; 9) Performance status 0-1 (ECOG PS); 10) Patient compliance to trial procedures; 11) Adequate bone marrow function (ANC = 1.5x109/L, platelets =100x109/L, haemoglobin >9 g/dl); 12) Adequate liver function (AST (SGOT)/ALT (SGPT) =2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be =5x ULN, bilirubin < grade 2, transaminases no more than 3xULN/<5xULN in presence of liver metastases); 13) Normal level of alkaline phosphatase, and creatinine; 14) Female patients should be using adequate contraceptive measures and should not be breastfeeding, until 4 months after the last dose, and must have a negative pregnancy test (serum or urine) prior to first dose of study drug (within 72 hours); or female patients must have an evidence of non-child-bearing potential by fulfilling one of the following criteria at screening: • Post-menopausal defined as aged 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 consider 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 post-menopausal range for the institution. • Documentation of irreversible surgical by hysterectomy, bilateraloophorectomy, or bilateral salpingectomy but not tubal ligation. 15) Male patients should be willing to use barrier contraception, i.e. condoms; 16) No significant comorbidity that according to the investigator would hamper the participation on the trial;
Exclusion Criteria
- Previous therapy with any EGFR-TKI; 2) Previous systemic anti-cancer therapy for advanced/metastatic NSCLC including chemotherapy, biologic therapy, immunotherapy, or any investigational drug; 3) Absence of measurable lesions; 4) Concomitant radiotherapy or chemotherapy; 5) Symptomatic or immediately requiring therapy brain metastases or carcinomatous meningitis. Subjects with asymptomatic and stable or treated brain metastases may participate; 6) Diagnosis of any other malignancy during the last 3 years, except for in situ carcinoma of cervix uteri and squamous cell carcinoma of the skin; 7) History of extensive disseminated/bilateral or known presence of Grade 3 or 4 interstitial fibrosis or interstitial lung disease including a history of pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia, interstitial lung disease, obliterative bronchiolitis and pulmonary fibrosis (but not history of prior radiation pneumonitis); 8) Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses, or active infection; 9) Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption of the study drugs; 10) Any of the following cardiac criteria: • Mean resting corrected QT interval (QTc) >470 msec, obtained from 3 ECGs using local clinic ECG machine-derived QTcF value; • Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG, e.g., complete left bundle branch block, third-degree heart block, seconddegree heart block, PR interval >250 msec or history of episodes of bradycardia (<50 BPM); • Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, 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; • Abnormal cardiac function: LVEF < 50% (assessed by MUGA or ECHO) 11) Pregnancy or lactating female; 12) Other serious illness or medical condition potentially interfering with the study. E.4.EN - Principal exclusion criteria (up to 4000 characters) (Criteri di esclusione principali, in inglese)
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Italy | Not Recruiting | 16 Jun 2020 | 163 |
 Spain | Not Yet Recruiting | 16 Jun 2020 | 26 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Vizimpro 15 mg film-coated tablets | Test | FILM-COATED TABLETS | ORAL | 45 | 36 | PRD7209574 |
TAGRISSO 80 mg film-coated tablets | Comparator | FILM-COATED TABLETS | ORAL | 80 | 36 | PRD3702398 |