A Three Cohort Phase II trial of BMS-275183 given orally on a twice weekly schedule in pretreated locally advanced or metastatic NSCLC patients

Phase 2

Conditions: lung cancer
10038666

Registration Number: NL-OMON29907

Lead Sponsor: Bristol-Myers Squibb

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Pending

Sex: Not specified

Target Recruitment: 12

Inclusion Criteria

1) Signed written informed consent 2) The subject population will consist of patients with histologically or cytologically confirmed locally advanced or metastatic NSCLC who failed only one prior chemotherapy regimen. 3) Prior chemotherapy with a minimum of two chemotherapy cycles given at a full dose. Prior chemo-radiation is not allowed unless the patient received a full dose of chemotherapy concomitantly with the radiation or the concomitant chemo-radiation was preceded or followed by a minimum of two cycles of the same chemotherapy administered at a full dose. That chemotherapy must be a taxane for cohort I, a platinum based but non taxane containing regimen for cohort II and any chemotherapy regimen and one EGFR-TKI inhibitor compound for cohort III patients. 4) Prior treatment with EGFR-TKI inhibitor is allowed only for patients in cohort 3. Prior treatment with a VEGFr inhibitor is allowed for all the patients. The VEGFr inhibitor cannot be in addition an EGFR inhibitor. 5) Prior chemotherapy may have been administered in adjuvant, neoadjuvant or advanced setting but only one prior chemotherapy regimen is allowed to which the patient must have failed treatment (i.e.: disease recurrence in adjuvant setting or tumor progression in advanced stages). 6) Patients must have at least one measurable lesion according to the SWOG criteria. 7) Prior anti cancer treatment must have been discontinued at least 3 weeks prior to study enrollment and the patient must have recovered from the acute toxicities of the prior treatment. 8) Prior radiation therapy must be completed at least 2 weeks prior to study enrollment and the patient must have recovered from its toxicities. 9) Prior curative surgery must have been completed at least 10 weeks, and prior palliative surgery must have been completed at least 2 weeks, prior to study enrollment. 10) Performance status of 0 or 1 on the ECOG scale or 90-100 on the Karnofsky scale (see Protocol Appendix 2). Adequate organ function is defined as: i) Adequate bone marrow function: absolute Neutrophil count of at least 1.5 x 10 9/L, platelets * 100 x 10 9 /L, and hemoglobin * 9 g/dl ii) Adequate hepatic function: Bilirubin less than or equal to the upper limit of normal (ULN), AST, ALT * 1.5 times ULN, and alkaline phosphatase * 2.5 ULN iii) Renal: Plasmatic creatinine < 1.5xULN 11) Estimate life*expectancy of a least 8 weeks 12) Men and women, age * 18 years 13) Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 8 weeks after the study in such a manner that the risk of pregnancy is minimized

Exclusion Criteria

Sex and Reproductive Status 1) WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and up to 8 weeks after the study. 2) Women who are pregnant or breastfeeding 3) Women with a positive pregnancy test on enrollment or prior to study drug administration. Target Disease Exceptions 4) Prior brain metastases, unless previously treated adequately, the patient is asymptomatic and no longer requires corticosteroids, and a minimum of 4 weeks has elapsed since the treatment of the brain lesions. Medical History and Concurrent Diseases 5) Second primary malignancy that is detectable at the time of consideration for study enrollment 6) Prior history of a major gastrointestinal surgery or malabsorption that could potentially influence the absorption of BMS-275183 7) Recent significant cardiovascular disease (i.e., myocardial infarction, unstable angina within 6 months, or any history of significant degree congestive heart failure with or without medical treatment, any history of clinically significant atrial or ventricular arrhythmias, any history of Grade 2 or 3 heart block). 8) QTc prolongation > 500 msec at the baseline 9) Serious concomitant systemic disorders that would compromise the safety of the patient or compromise the patient*s ability to complete the study 10) Prior treatment with BMS-275183 11) Active infection that, in the opinion of the investigator, is not compatible with the conduct of the study. Physical and Laboratory Test Findings 12) Inability or unwillingness to swallow the oral BMS-275183 13) NCI CTC AE Grade * 2 peripheral neuropathy at study entry. 14) Significant weight loss, (i.e. * 10%, over the previous 6 weeks before study entry) Prohibited Therapies and/or Medications 15) Concomitant medication with efflux transporter PGP inhibitors such as Benzimidazoles (benzimidazoles includes PPIs such as omeprazole, esomeprazole, lansoprazole, pantoprazole) or prior medication with such drugs within seven days from study drug administration 16) Concomitant medication with a CYP 3A4 inhibitor or inducer (see Protocol Appendix 3). 17) Concomitant medication with Metoclopramide Other Exclusion Criteria 18) Prisoners or subjects who are compulsorily detained

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The primary objective of the trial is to assess efficacy of BMS-275183 in<br /><br>pretreated NSCLC patients as measured by tumor response rate according to the<br /><br>SWOG criteria.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Qualitative and quantitative toxicityies of BMS-275183<br /><br>Response duration.<br /><br>Progression free survival time.<br /><br>Overall survival time.<br /><br>Plasma pharmacokinetics of BMS-275183 at the recommended dose of 100 mg/m²<br /><br>given orally on a twice weekly schedule (Cmax, Tmax, AUC(INF), T-HALFCL/F).</p><br>