Study of Safety and Efficacy of Brigatinib Plus Chemotherapy or Brigatinib Only in Advanced ALK-Positive Lung Cancer (MASTERPROTOCOL ALK)

  • STATUS
    Recruiting
  • End date
    Oct 10, 2028
  • participants needed
    110
  • sponsor
    Intergroupe Francophone de Cancerologie Thoracique
Updated on 4 October 2022
brigatinib
lipase
serum bilirubin level
progressive disease
pemetrexed
neutrophil count
carboplatin
cancer chemotherapy
kidney function test
lung carcinoma

Summary

This is a phase II randomized, open-labelled, non-comparative multicenter study in which ALK+ NSCLC patients who are naïve of treatment for advanced disease will be randomized to receive brigatinib monotherapy (Arm A) or brigatinib and carboplatin-pemetrexed therapy (Arm B). An estimated 110 patients (55 in Arm A, 55 in Arm B) will be enrolled at approximately 30 centers. A safety phase will evaluate the safety of brigatinib with carboplatin and pemetrexed treatment combination (Arm B). The first twenty-six patients enrolled in Arm B will represent the population of the safety phase. Patients will be treated until they experience progressive disease, intolerable toxicity, or another discontinuation criterion is met. Continuation of brigatinib beyond progression is permitted, at the investigator's discretion, if there is evidence of continued clinical benefit. The null hypothesis is progression free survival at 12 months ≤ 69% for Arm B, which is considered not sufficiently clinically meaningful to warrant further study. The alternative hypothesis is that 86% or more of patients in Arm B would achieve progression free survival at 12 months.

Details
Condition Non Small Cell Lung Cancer, ALK Gene Mutation
Treatment carboplatin, Pemetrexed, Brigatinib 180 MG
Clinical Study IdentifierNCT05200481
SponsorIntergroupe Francophone de Cancerologie Thoracique
Last Modified on4 October 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Subjects must have signed and dated an IRB/IEC approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol related procedures that are not part of normal subject care. Subjects must be willing and able to comply with scheduled visits, treatment schedule, and laboratory testing
Patients diagnosed with histologically or cytologically confirmed locally advanced not eligible to a local treatment or metastatic NSCLC (Stage IIIB, IIIC or IV accordingly to 8th classification TNM, UICC 2015)
Patients are eligible for trial entry on the basis of locally determined ALK testing. ALK Immunohistochemistry (IHC) assay (3+ only), DNA-based or RNA-based next generation sequencing (NGS) assay or nCounter Nanostring assay performed locally are accepted ALK testing assays after review by the promotor. If ALK rearrangement diagnostic is performed using IHC and the result is + or 2+, a confirmation with a second method performed locally (DNA-based or RNA-based next generation sequencing (NGS) assay, nCounter Nanostring assay or ALK FISH performed) is required
All Patients must have at least one measurable target lesion according to RECIST v1.1 per investigator assessment. The radiological assessment has to be done within the timelines indicated
Patients with asymptomatic and neurologically stable CNS metastases (including patients controlled with less than 10mg/day of methylprednisolone within the last week prior to study entry) will be eligible
Tumor Sample Requirement: sufficient tumor tissue for central analysis should be available (tumor block or a minimum of 10 unstained slides of 4 µm of analyzable tissue)
Age ≥18 years
Life expectancy of at least 12 weeks, in the opinion of the Investigator
Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1
Adequate Bone Marrow Function, including: Absolute Neutrophil Count (ANC) ≥1.5 x 109/L; Platelets ≥100 x 109/L; Hemoglobin ≥9 g/dL
Adequate Pancreatic Function, including: Serum lipase ≤1.5 ULN
Adequate Renal Function, including: Estimated creatinine clearance ≥45 mL/min as calculated using the standard method of the institution
Adequate Liver Function, including: Total serum bilirubin ≤1.5 x ULN (<3.0 × ULN for patients with Gilbert syndrome); Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤2.5 x ULN; ≤5.0 x ULN if there is liver metastases involvement
Participants must have recovered from toxicities related to prior anticancer therapy to CTCAE Grade ≤ 1
Participants must have recovered from effects of any major surgery, or significant traumatic injury, at least 35 days before the first dose of treatment
Have normal QT interval on screening ECG evaluation, defined as QT interval corrected (Fridericia) (QTcF) of ≤450 milliseconds (msec) in males or ≤470 msec in females
Female patients who: are postmenopausal for at least 1 year before the screening visit, OR are surgically sterile, OR if they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, one of them being nonhormonal, from the time of signing the informed consent through 6 months after the last dose of study drug, or agree to completely abstain from heterosexual intercourse
Male patients, even if surgically sterilized (i.e., status post-vasectomy), who: agree to practice effective barrier contraception during the entire study treatment period and through 6 months after the last dose of study drug, or agree to completely abstain from heterosexual intercourse
Willingness and ability to comply with the study scheduled visits, treatment plans, laboratory tests and other procedure
Participant has national health insurance coverage

Exclusion Criteria

Previously received an investigational antineoplastic agent for NSCLC
Previously received any prior TKI, including ALK-targeted TKIs
Known molecular co-alteration i.e. activating EGFR/BRAF/KRAS/MET mutation and ROS1/RET/NTRK fusion
Previously received neo-adjuvant or adjuvant systemic chemotherapy or consolidation immunotherapy if completion of (neo) adjuvant/consolidation therapy occurred <12 months prior to randomization
Patients who have leptomeningeal disease (LM) or carcinomatous meningitis (CM) according to MRI data and/or in case of documented cerebral spinal fluid (CSF) positive cytology
Spinal cord compression
Patients with symptomatic or neurologically instable CNS metastases
Major surgery within 30 days of study entry. Minor surgical procedures (e.g., port insertion, mediastinoscopy, surgical procedure for re-sampling) are not excluded, but sufficient time at investigator discretion should have passed for wound healing
Radiation therapy within 2 weeks of study entry. Stereotactic or small field brain irradiation must have completed at least 2 weeks prior to study entry. Whole brain radiation must have completed at least 4 weeks prior to study entry
Active and clinically significant bacterial, fungal, or viral infection including hepatitis B (HBV), hepatitis C (HCV), known human immunodeficiency virus (HIV), or acquired immunodeficiency syndrome (AIDS)-related illness
Have significant, uncontrolled, or active cardiovascular disease, specifically including, but not restricted to: a) myocardial infarction within 6 months prior to the first dose of study drug; b) unstable angina within 6 months prior to the first dose of study drug; c) congestive heart failure within 6 months prior to the first dose of study drug; d) any history of ventricular arrhythmia; e) history of clinically significant atrial arrhythmia or clinically significant bradyarrhythmia as determined by the treating physician; f) cerebrovascular accident or transient ischemic attack within 6 months prior to the first dose of study drug
Have uncontrolled hypertension. Patients with hypertension should be under treatment on study entry to control blood pressure
History of grade 3 or 4 of interstitial fibrosis or interstitial lung disease including a history of pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia, interstitial lung disease, obliterative bronchiolitis, pulmonary fibrosis and radiation pneumonitis
Presence of interstitial fibrosis of any grade at baseline
Other severe acute or chronic medical or psychiatric condition, including recent (within the past year) or active suicidal ideation or behavior, or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study
Evidence of active malignancy (other than current NSCLC, non-melanoma skin cancer, in situ cervical cancer, papillary thyroid cancer, DCIS of the breast or localized and presumed cured prostate cancer) within the last 3 years
Active inflammatory gastrointestinal disease, malabsorption syndrome, chronic diarrhea, symptomatic diverticular disease or previous gastric resection or lap band
Current use or anticipated need for food or drugs prohibited
Patients presenting with abnormal Left Ventricular Ejection Fraction (LVEF) by echocardiogram or Multi-Gated Acquisition Scan (MUGA) according to institutional lower limits
Have a known or suspected hypersensitivity to brigatinib, carboplatin or pemetrexed or their excipients
Female patients who are both lactating and breastfeeding or have a positive serum pregnancy test during the screening period or a positive urine pregnancy test on Day 1 before first dose of study drug
Received systemic treatment with strong cytochrome p-450 (cyp)3a inhibitors, strong cyp3a inducers, or moderate cyp3a inducers within 14 days before enrolment
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