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Ceritinib and Docetaxel in Treating Patients with Stage IIIB / IV ALK-Negative and EGFR Wild-Type Non-small Cell Lung Cancer

Trial Status: Active

This phase I trial studies the best dose and side effects of ceritinib and docetaxel in treating patients with stage IIIB / IV ALK-negative and EGFR wild-type non-small cell lung cancer. Ceritinib and docetaxel may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving ceritinib and docetaxel may work better in treating patients with non-small cell lung cancer.

Inclusion Criteria

  • Ability to understand and provide informed consent
  • Willingness and ability to comply with scheduled study visits and procedures
  • Histologic or cytologic diagnosis of advanced/metastatic non-small cell lung cancer (NSCLC) (stage IIIB/IV)
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • No more than three prior regimens for stage IIIB/IV disease, with at least one prior regimen (for any stage) containing a platinum-based agent. Prior PD-1 or PD-L1 antibody-based regimen are allowable and counts as a prior regimen. Prior therapy with a taxane is allowed. Patients progressing within 6 months of platinum-based chemotherapy for stage I-IIIA disease are allowed
  • Patients enrolled on the phase 1b expansion portion of the trial must be willing and able to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion. Newly-obtained is defined as a specimen obtained up to 3 months prior to initiation of treatment on day 1, and must be obtained after most recent tumor progression. Subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen only upon agreement from the sponsor
  • Prior radiation is allowed if patients have recovered from side effects
  • Patients with a prior history of brain metastases are eligible, provided: * The brain metastases have been treated * The patient is asymptomatic from the brain metastases * Corticosteroids prescribed for the management of brain metastases have been discontinued at least 7 days before registration to study * The brain metastases are stable on pre-registration imaging * There is no evidence of leptomeningeal disease
  • Measurable metastatic disease according to Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 criteria
  • Life expectancy > 3 months
  • Absolute neutrophil count (ANC) >= 1.5 x 10^9/L
  • Hemoglobin >= 90 g/L (or >= 9 g/dL)
  • Platelets >= 100 x 10^9/L
  • Calculated creatinine clearance of > 50 mL/min using Cockcroft Gault equation
  • Total bilirubin =< 1.5 institutional upper limit of normal
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal * If Alkaline phosphatase >= 2.5 x institutional upper limit of normal, then AST and ALT must be =< 1.5 x institutional upper limit of normal
  • Serum amylase and lipase =< 2 x institutional upper limit of normal
  • Fridericia's corrected QT interval (QTcF) =< 470 msec (using Fridericia’s correction on the screening electrocardiogram [ECG] as mean of triplicate ECGs)
  • Potassium at or above the lower institutional limits of normal, or have the values corrected with supplements to be at or above the lower normal limits before the first dose of ceritinib
  • Magnesium at or above the lower institutional limits of normal, or have the values corrected with supplements to be at or above the lower normal limits before the first dose of ceritinib
  • Phosphorus at or above the lower institutional limits of normal, or have the values corrected with supplements to be at or above the lower normal limits before the first dose of ceritinib
  • Total calcium (corrected for serum albumin) at or above the lower institutional limits of normal, or have the values corrected with supplements to be at or above the lower normal limits before the first dose of ceritinib
  • Patients of child bearing age must not be pregnant and must use established contraceptive strategies: * Female subjects of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required * Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year * Male subjects should agree to use an adequate method of barrier contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy

Exclusion Criteria

  • Rearrangements in ALK
  • Activating mutations in EGFR
  • Patients with active malignancies other than NSCLC, or prior curatively treated malignancy at high risk of relapse during the study period with the exception of localized squamous or basal cell skin cancers
  • Pregnant or breast feeding
  • Known hypersensitivity to ceritinib, docetaxel, or any of their excipients
  • Serious uncontrolled medical disorder, psychiatric condition or laboratory abnormalities that, in the opinion of the investigator, may increase the risk associated with study participation or may interfere with the interpretation of study results
  • Patient has had major surgery (e.g., intra-thoracic, intra-abdominal or intra-pelvic) within 4 weeks prior to starting study treatment or has not recovered from side effects of such procedure. Video-assisted thoracic surgery (VATS) and mediastinoscopy are exceptions and patients can receive study treatment >= 1 week after these procedures
  • Patient has history of clinically significant noninfectious interstitial pneumonitis (i.e., limiting activities of daily living or requiring therapeutic intervention), including clinically significant radiation pneumonitis
  • Residual toxicity from prior anticancer therapy of grade 3 or greater (Common Terminology Criteria for Adverse Events [CTCAE] v 5.0), with the exception of alopecia
  • Concurrent use of other anticancer approved or investigational agents (including radiation therapy) within 2 weeks of the first dose of study treatment
  • In taxane pretreated patents, any history of dose-limiting toxicity with prior taxane therapy
  • Patients with clinically significant, uncontrolled heart disease and/or recent cardiac event (within 6 months), such as: * Unstable angina within 6 months prior to screening * Myocardial infarction within 6 months prior to screening * History of documented congestive heart failure (New York Heart Association functional classification III-IV) * Cardiac arrhythmias not controlled with medication
  • Uncontrolled diabetes mellitus, defined as fasting plasma glucose > 200 mg/dL
  • Impaired gastrointestinal (GI) function or GI disease that may alter absorption of ceritinib, or inability to swallow capsules
  • Receiving medications that meet one of the following criteria and that cannot be discontinued at least 1 week prior to the start of treatment with ceritinib and for the duration of participation * Medication with a known risk of prolonging QT interval or inducing Torsades de Pointes * Strong inhibitors or strong inducers of CYP3A4/5 * Medications with a low therapeutic index that are primarily metabolized by CYP3A4/5, and/or CYP2C9 * Therapeutic doses of warfarin sodium (Coumadin) or any other coumadin-derived anti-coagulant. Anticoagulants not derived from warfarin are allowed (e.g., dabigatran, rivaroxaban, apixaban) * Enzyme-inducing anticonvulsive agents * Herbal medications, including, but not limited to: St. John’s wort, Kava, ephedra (mahuang), gingko biloba, dehydroepiandrosterone (DHEA), yohimbe, saw palmetto, and ginseng


AdventHealth Orlando
Status: ACTIVE
Contact: Mark Anthony Socinski
Phone: 407-200-2901
Moffitt Cancer Center
Status: ACTIVE
Contact: Andreas Saltos
Phone: 813-745-5373


I. To determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of concurrent administration of ceritinib and docetaxel, and describe adverse event profile. (Phase I)

II. To estimate response rates of patients treated with ceritinib and docetaxel. (Phase Ib)


I. To examine potential predictive markers in the tumors of clinical responders.

II. To determine the overall survival (OS), disease control rate (DCR), and progression-free survival (PFS) of patients treated with ceritinib and docetaxel. (Phase Ib)

OUTLINE: This is a phase I, dose-escalation study followed by a phase Ib study.

Patients receive ceritinib orally (PO) on days 1-21 and docetaxel intravenously (IV) on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days, every 3 months for 1 year, and then every 6 months for up to 5 years.

Trial Phase Phase I

Trial Type Treatment

Lead Organization
Moffitt Cancer Center

Principal Investigator
Andreas Saltos

  • Primary ID MCC-19656
  • Secondary IDs NCI-2018-02598
  • ID NCT03611738