A Three Cohort Phase II Trial of BMS-275183 Given Orally on a Twice Weekly Schedule in Pretreated Locally Advanced or Metastatic NSCLC Patients - CA165-026

Conditions: Pretreated Locally Advanced or Metastatic Non Small Cell Lung Cancer
MedDRA version: 9.1Level: LLTClassification code 10062042Term: Lung neoplasm

Registration Number: EUCTR2005-005099-33-IT

Lead Sponsor: Bristol Myers Squibb International Corporation

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 186

Inclusion Criteria

1 Signed written informed consent Target population 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 enrolment 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 Appendix 2 . a Adequate organ function is defined as i Adequate bone marrow function absolute Neutrophil count of at least 1.5 x 10 9/L, platelets 8805; 100 x 10 9 /L, and hemoglobin 8805; 9 g/dl ii Adequate hepatic function Bilirubin less than or equal to the upper limit of normal ULN , AST, ALT 8804; 1.5 times ULN, and alkaline phosphatase 8804; 2.5 ULN iii Renal Plasmatic creatinine 1.5xULN 11 Estimate life expectancy of a least 8 weeks Age and Sex 12 Men and women, age 18 years 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 WOCBP must have a negative serum or urine pregnancy test minimum sensitivity 25 IU/L or equivalent units of HCG within 72 hours prior to the start of study medication.
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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

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 BMS275183 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 61601; 61661; 61472;2 peripheral neuropathy at study entry. 14 Significant weight loss, i.e. 8805; 10 , over the previous 6 weeks before study entry Allergies and Adverse Drug Reactions Not applicable 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 Appendix 3 . 17 Concomitant medication with Metoclopramide Other Exclusion Criteria 18 Prisoners or subjects who are compulsorily detained involuntarily incarcerated for treatment of either a psychiatric or physical e.g., infectious disease illness must not be enrolled into this study

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess efficacy of BMS-275183 in pretreated NSCLC patients as measured by the tumor response rate.;Secondary Objective: To further characterize the qualitative and quantitative toxicities of BMS-275183 in the same patient population. To assess the response duration. To assess the progression free survival time. To assess the overall survival time. To assess the plasma pharmacokinetics PK of BMS-275183 at the recommended dose of 100 mg/m given orally on a twice weekly schedule.;Primary end point(s): To assess efficacy of BMS-275183 in pretreated NSCLC patients as measured by the tumor response rate. To further characterize the qualitative and quantitative toxicities of BMS-275183 in the same patient population. To assess the response duration. To assess the progression free survival time. To assess the overall survival time. To assess the plasma pharmacokinetics PK of BMS-275183 at the recommended dose of 100 mg/m given orally on a twice weekly schedule.

Secondary Outcome Measures