SCH 727965 in Patients With Advanced Breast and Lung Cancers (Study P04716)

Study Overview
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Brief Summary
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To determine the activity of SCH 727965 in participants with breast cancer and in participants with nonsmall-cell lung cancer (NSCLC) compared to standard treatment. The standard treatment used is capecitabine for breast cancer and erlotinib for NSCLC. The study will also determine the activity of SCH 727965 treatment in participants who experience cancer progression after standard treatment.

Official Title
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A Randomized Phase 2 Study of SCH 727965 in Subjects With Advanced Breast and Non Small Cell Lung (NSCLC) Cancers

Conditions
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Breast Neoplasms, Carcinoma, Non-Small-Cell Lung

Intervention / Treatment
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* Drug: SCH 727965
* Drug: Capecitabine
* Drug: Erlotinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age >=18 years, either sex, any race. Histologically or cytologically confirmed breast cancer or NSCLC; and radiographic or clinically advanced disease. BREAST CANCER: participant must have previously received both a taxane and an anthracycline (unless anthracycline therapy is contraindicated) in the adjuvant and/or metastatic setting, participant with HER2-positive disease must have progressed after trastuzumab and concomitant or subsequent lapatinib, participant must have received at least one, but no more than two prior regimens for recurrent or metastatic disease (endocrine and biologic therapies do not count as chemotherapeutic regimens). NSCLC: at least one, but no more than two prior chemotherapeutic regimens for advanced disease. Measurable disease by the RECIST. Eastern Cooperative Oncology Group performance status of 0, 1, or 2. Adequate hematologic, renal, and hepatic organ function and laboratory parameters. Ability to swallow tablets. Exclusion Criteria: Known brain metastases. For NSCLC only, a participant with central nervous system metastasis is eligible provided the participant has received definitive local therapy (ie, radiation therapy or surgery), has stopped receiving treatment with corticosteroids, and is without symptoms for at least 4 weeks before randomization. History of previous radiation therapy to >25% of total bone marrow. Known HIV infection. Known active hepatitis B or hepatitis C. Previous treatment with SCH 727965 or other cyclin-dependent-kinase inhibitors. BREAST CANCER: known dihydropyrimidine dehydrogenase deficiency, previous treatment with capecitabine. NSCLC: previous treatment with erlotinib.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Breast cancer randomized to SCH 727965<br> | Drug: SCH 727965<br>* SCH 727965 50 mg/m^2 IV on Day 1 of each 21 day cycle until disease progression.<br>|
| Active Comparator: Breast cancer randomized to capecitabine<br> | Drug: Capecitabine<br>* Capecitabine 1250 mg/m^2 orally twice daily from Day 1 to Day 14 of each 21 day cycle until disease progression.<br>* Other names: Xeloda;|
| Experimental: SCH 727965 in breast cancer after progression on capecitabine<br> | Drug: SCH 727965<br>* SCH 727965 50 mg/m^2 IV on Day 1 of each 21 day cycle until disease progression.<br>|
| Experimental: NSCLC randomized to SCH 727965<br>Note: Enrollment of participants with NSCLC was completed per protocol as of 26 JAN 2010 | Drug: SCH 727965<br>* SCH 727965 50 mg/m^2 IV on Day 1 of each 21 day cycle until disease progression.<br>|
| Active Comparator: NSCLC randomized to erlotinib<br>Note: Enrollment of participants with NSCLC was completed per protocol as of 26 JAN 2010 | Drug: Erlotinib<br>* Erlotinib 150 mg orally once daily until disease progression.<br>* Other names: Tarceva;|
| Experimental: SCH 727965 in NSCLC after progression on erlotinib<br>Note: Crossover to SCH 727965 after progression on erlotinib was completed per protocol as of 26 JAN 2010 | Drug: SCH 727965<br>* SCH 727965 50 mg/m^2 IV on Day 1 of each 21 day cycle until disease progression.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to disease progression. | Date of randomization to date of tumor progression. | Every 6 weeks for 30 weeks, and then every 9 weeks. Assessments continue until disease progression. | 
| Overall response rate in participants treated with SCH 727965 after disease progression on the comparator drug. | Percentage of participants with tumor responses (partial responses + complete responses). | Every 6 weeks for 30 weeks, and then every 9 weeks. |