A Randomized, Double-Blind Phase 2 Study of Ruxolitinib or Placebo in Combination With Pemetrexed/Cisplatin and Pemetrexed Maintenance for Initial Treatment of Subjects With Nonsquamous Non-Small Cell Lung Cancer That Is Stage IIIB, Stage IV, or Recurrent
- Conditions
- niet-squamous, niet-kleincellig longcarcinoomlungcancer
- Registration Number
- NL-OMON41950
- Lead Sponsor
- Incyte Corporation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 25
•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 Cycle 1 Day 1, 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: C-reactive protein > 10 mg/L AND albumin >= 35 g/L Score: 1
Criteria: C-reactive protein > 10 mg/L AND albumin < 35 g/L Score: 2
•Radiographically measurable or evaluable disease.
*- Measurable lesions may be in the field of prior radiation; however, there must be at least a 4 week period between the last radiation treatment and demonstration of interval progression of the lesion compared with the baseline scan documenting disease status for the lesion to be considered measurable.
•Life expectancy of at least 12 weeks.
•Tumor without activating driver mutations for which there is an available therapy (eg, tumor without mutations in EGFR or anaplastic lymphoma kinase).
•ECOG performance status of 0 to 1.
•Adequate renal, hepatic, and bone marrow function demonstrated by protocol-specified laboratory parameters at the screening visit:
- Absolute neutrophil count >= 1.5 × 109/L.
- Platelet count >= 100 × 109/L.
- Hemoglobin >= 85 g/L (transfusion support to maintain this hemoglobin level is acceptable).
- Alanine aminotransferase and aspartate aminotransferase <= 2.5 × upper limit of laboratory normal (ULN) or <= 5 × ULN in the presence of liver metastases.
- Total bilirubin <= 1.5 × ULN; if total bilirubin is > 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 (defined as women who have not undergone surgical sterilization with a hysterectomy and/or bilateral oophorectomy, and are not postmenopausal, defined as >=12 months of amenorrhea) 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. Permitted methods that are at least 99% effective in preventing pregnancy should be communicated to the subject and their understanding confirmed.
•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.
•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 (eg, packed red blood cells, platelets).
•Prior treatment with any JAK inhibitor.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary Endpoints:<br /><br>• Part 1: Determination of the dose of ruxolitinib that is safe and tolerable<br /><br>in combination with pemetrexed/cisplatin.<br /><br>• Part 2: Overall survival as determined from the date of randomization until<br /><br>death due to any cause.</p><br>
- Secondary Outcome Measures
Name Time Method <p>Secondary Endpoints:<br /><br>• Progression-free survival as determined from the randomization date until the<br /><br>earliest date of disease progression, as measured by investigator assessment of<br /><br>objective radiographic disease assessments per RECIST (v1.1), or death due to<br /><br>any cause if earlier.<br /><br>• Objective response rate and duration of response determined by radiographic<br /><br>disease assessments per RECIST (v1.1).<br /><br>• Safety and tolerability of the treatment regimens assessed by monitoring the<br /><br>frequency, duration and severity of AEs; performing physical examinations; and<br /><br>evaluating change in vital signs and laboratory results.</p><br>