A Randomized, Placebo-Controlled Phase 2b Study of Tamibarotene Plus Paclitaxel and Carboplatin Versus Placebo Plus Paclitaxel and Carboplatin as First Line Treatment for Subjects With Advanced Non-Small Cell Lung Cancer
Overview
- Phase
- Phase 2
- Intervention
- Tamibarotene
- Conditions
- Stage IIIB Non-small Cell Lung Cancer With Pleural Effusion
- Sponsor
- CytRx
- Enrollment
- 140
- Locations
- 26
- Primary Endpoint
- Progression-free survival
- Status
- Terminated
- Last Updated
- 12 years ago
Overview
Brief Summary
The goal of this study is to determine the progression-free survival and objective response rate in subjects with either stage IIIB with pleural effusion NSCLC or stage IV NSCLC who are treated with up to six cycles of paclitaxel plus carboplatin and either tamibarotene or placebo. Subjects will be randomly assigned to receive tamibarotene, 6 mg/m2, divided as twice daily orally, or an equal number of matching placebo tablets, starting 1 week before chemotherapy and continuing through all 6 cycles and beyond. Subjects will be assessed for response on Day 50, Day 113, then every other month using the Response Evaluation Criteria in Solid Tumors (RECIST 1.1).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Subjects must be at least 18 years of age
- •Subjects must have pathological findings consistent with primary non-small cell lung cancer of any histology.
- •Subjects must have either stage IIIB with pleural effusion or IV NSCLC with radiographically measurable disease (RECIST 1.1 criteria). Women non-smokers with stage IV NSCLC should be screened for EGFR mutation and if positive be excluded from the study and placed on an EGFR kinase inhibitor.
- •Subjects must have an ECOG Performance Status ≤
- •If corticosteroids are required for controlling cerebral edema, subjects must be on a stable dose for at least 1 week.
- •Subjects must have recovered from any toxicity of prior therapies.
- •Subjects must be at least 4 weeks removed from surgery or radiation therapy.
- •Subjects must have a life expectancy of at least 12 weeks.
- •Subjects must have adequate bone marrow function (defined as an absolute neutrophil count of ≥1500 cells/mm3 and platelet count ≥100,000 cells/mm3), liver function with total bilirubin ≤2.0 mg/dL, and serum creatinine ≤1.5 x institutional ULN.
- •Subjects must be able to understand and be willing to sign a written informed consent document.
Exclusion Criteria
- •Subjects who have received or are currently receiving chemotherapy or antibody therapy, or are enrolled in another treatment clinical trial.
- •Subjects with a coagulopathy or bleeding disorder.
- •Clinically evident congestive heart failure \>class II of the New York Heart Association (NYHA) guidelines.
- •Serious, clinically significant cardiac arrhythmias, defined as the existence of an absolute arrhythmia or ventricular arrhythmias classified as Lown III, IV or V.
- •History or signs of active coronary artery disease with or without angina pectoris (i.e. myocardial infarction with 6 months prior to enrollment, uncontrolled angina, electrocardiographic evidence of acute ischemia).
- •Subjects who have a serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol or may not be able to comply with the safety monitoring requirements of the study.
- •HIV-positive subjects; however, subjects will not be routinely screened for HIV.
- •Subjects who are allergic to any of the intended chemotherapies.
- •Female subjects who are pregnant or breast-feeding.
- •Active, clinically significant serious infection requiring treatment with antibiotics, antivirals, or antifungals.
Arms & Interventions
Tamibarotene
Subjects will receive tamibarotene, 6 mg/m2, divided as twice daily orally starting 1 week before chemotherapy and continuing through all 6 cycles and through the duration of the study. Chemotherapy will include paclitaxel (IV; 200 mg/m2) and carboplatin (IV; AUC=6)administered once every 3 weeks for up to 6 cycles.
Intervention: Tamibarotene
Placebo
Subjects will take an equal number of placebo tablets as the group receiving tamibarotene divided as twice daily orally, starting 1 week before chemotherapy and continuing through all 6 cycles and through the duration of the study. Paclitaxel (IV; 200 mg/m2) and carboplatin (IV; AUC=6) will be administered once every 3 weeks for up to 6 cycles.
Intervention: Placebo
Outcomes
Primary Outcomes
Progression-free survival
Time Frame: Within 18 months of study start.
Progression-free survival (PFS) is defined as the time from enrollment (i.e., assignment of subject ID number) to first documentation of objective tumor progression or to death due to any cause in the absence of previous documentation of objective tumor progression.
Secondary Outcomes
- Objective response rate(Within 18 months of study start.)
- Overall survival(Within 24 months of study start.)
- Assessment of quality of life(Within 24 months of study start.)