Nonsquamous NSCLC that is Stage IIIB, Stage IV, or recurrent MedDRA version: 17.1 Level: PT Classification code 10029522 Term: Non-small cell lung cancer stage IV System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 17.1 Level: PT Classification code 10029521 Term: Non-small cell lung cancer stage IIIB System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 17.1 Level: PT C
Conditions
Interventions
Trade Name: Jakafi
Product Name: ruxolitinib
Product Code: INCB018424
Pharmaceutical Form: Tablet
INN or Proposed INN: ruxolitinib
CAS Number: N/A
Current Sponsor code: INCB018424
Other descriptive na
Sponsors
Incyte Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: •Men or women aged 18 or older. •Histologically or cytologically confirmed diagnosis of nonsquamous NSCLC that is Stage IIIB, Stage IV, or recurrent after prior definitive intervention (radiation, surgery, or chemoradiation therapy, with or without adjuvant or neoadjuvant chemotherapy). ? Subjects who have recurrent NSCLC after prior surgery or radiation therapy are allowed to enter. At least 4 weeks must have elapsed between prior radiation therapy and screening, and all radiation therapy–related toxicities must have resolved. ? Subjects who have received radiation to the spine, pelvis, ribs, or femur should be discussed with the sponsor, as extensive radiation to marrow-forming region may compromise a subject's ability to tolerate myelosuppressive chemotherapy. ? Subjects must not have received prior chemotherapy for advanced or metastatic disease. •An mGPS of 1 or 2 as defined below: Criteria Score C-reactive protein > 10 mg/L AND albumin = 35 g/L 1 C-reactive protein > 10 mg/L AND albumin 1.5 × ULN, then direct bilirubin must be = 1.5 × ULN. ? Creatinine clearance = 50 mL/min measured or calculated by Cockroft-Gault equation, or glomerular filtration rate = 50 mL/min/1.73 m2 as calculated using the Modification of Diet in Renal Disease formula. •Female subjects of childbearing potential must have a negative serum pregnancy test at screening. All female subjects of childbearing potential must agree to take appropriate precautions to avoid pregnancy (with at least 99% certainty) from screening to follow-up. •Male subjects must agree to take appropriate precautions to avoid fathering children (with at least 99% certainty) from screening through follow-up. Permitted methods that are at least 99% effective in preventing pregnancy should be communicated to the subject and their understanding confirmed. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 85 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 91
Exclusion criteria
Exclusion criteria: •Squamous or mixed histology (eg, adenosquamous) NSCLC •Previous systemic therapy for advanced or metastatic disease. (Subjects who completed a platinum-containing regimen as adjuvant, neoadjuvant, or part of a course of chemoradiation therapy within the 6 months before screening are also excluded.) •Known active (untreated) central nervous system (CNS) metastases. Subjects with CNS metastases who have completed a course of therapy would be eligible for the study provided they are clinically stable for at least 4 weeks before study entry, defined as: •No evidence of new or enlarging CNS metastasis or new neurological symptoms attributable to CNS metastases. •Asymptomatic and receiving either no or stable doses of anticonvulsants and/or corticosteroids for the 4 weeks prior to study entry. •Current or previous other malignancy within 2 years of study entry, except cured basal or squamous cell skin cancer, superficial bladder cancer, prostate intraepithelial neoplasm, carcinoma in situ of the cervix, or other noninvasive or indolent malignancy without sponsor approval. •Current uncontrolled cardiac disease such as angina or myocardial infarction, congestive heart failure including New York Heart Association functional classification of 3, or arrhythmia requiring treatment. •Uncontrolled concomitant medical conditions, including, but not limited to, renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, neurological, cerebral, or psychiatric diseases. •Known hypersensitivity to any of the active substances or any of their excipients, including ruxolitinib, cisplatin, or pemetrexed. •Inability to take brief courses of dexamethasone each month. •Unwillingness or inability to take vitamin B12 and folic acid supplements. •Chronic or current active infectious disease requiring systemic antibiotics, antifungals, or antivirals. •Known HIV-positive status. •Hepatitis B virus (HBV) or hepatitis C virus (HCV) viremia or at risk for HBV reactivation. HBV DNA and testing for HCV RNA must be undetectable. At risk for HBV reactivation is defined as hepatitis B surface antigen positive or anti-hepatitis B core antibody positive. •Pregnant or breastfeeding women. •Unwillingness to be transfused with blood components •Prior treatment with any JAK inhibitor.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: •Part 1: To evaluate the safety and tolerability of ruxolitinib in combination with pemetrexed/cisplatin and select a dose for further evaluation •Part 2: To evaluate and compare the OS of subjects with nonsquamous NSCLC that is Stage IIIB, Stage IV, or recurrent when treated with ruxolitinib or placebo in combination with pemetrexed/cisplatin and subsequently pemetrexed maintenance ;Secondary Objective: •To evaluate and compare the efficacy of the 2 treatment arms with respect to PFS •To evaluate and compare the efficacy of the 2 treatment arms with respect to overall tumor response and duration of response •To evaluate and compare the safety and tolerability of ruxolitinib in combination with pemetrexed/cisplatin versus pemetrexed/cisplatin alone ;Primary end point(s): •Part 1: Determination of the dose of ruxolitinib that is safe and tolerable in combination with pemetrexed/cisplatin. •Part 2: Overall survival as determined from the date of randomization until death due to any cause. ;Timepoint(s) of evaluation of this end point: The primary endpoint is OS, defined as number of days from randomization to death. This analysis will be based on the intent-to-treat population, according to treatment assignment. Survival data will be analyzed by the Kaplan-Meier method stratified by mGPS score, treating subjects with no observed death as censored at their last date known to be alive. The Arm1/Arm2 HR and its 80% CI will be estimated using Cox regression model with mGPS score as covariate. The OS will also be analyzed based on per-protocol population as sensitivity analysis. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •Progression-free survival as determined from the randomization date until the earliest date of disease progression, as measured by investigator assessment of objective radiographic disease assessments per RECIST (v1.1), or death due to any cause if earlier. •Objective response rate and duration of response determined by radiographic disease assessments per RECIST (v1.1). •Safety and tolerability of the treatment regimens assessed by monitoring the frequency, duration, and severity of AEs; performing physical examinations; and evaluating change in vital signs and laboratory results. ;Timepoint(s) of evaluation of this end point: Progression-free survival will be determined from the randomization date until the earliest date of disease progression, as measured by investigator assessment of objective radiographic disease assessments per RECIST (v1.1), or death due to any cause if earlier. The rates of responders will be compared with Cochran–Mantel–Haenszel test stratified by mGPS score. The duration of response is defined as the difference of the end of response and the start of response for subjects who have at least one response measurement. The start of a response will be the first visit where the subject achieves PR or better based on RECIST v1.1 criteria. The end of response will be the first visit after PD based on RECIST v1.1 criteria. | — |
Countries
Denmark, Hong Kong, Italy, Korea, Republic of, Malaysia, Netherlands, Portugal, Spain, United States
Contacts
Public ContactInformation Centre
Incyte Corporation
Outcome results
None listed