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The purpose of this study is to determine the maximum tolerable dose of temozolomide in combination with fixed dose of paclitaxel and carboplatin and to determine the overall tumor response rate with this combination and to determine the duration of response.
The objective of the research study is to test a combination of drugs to treat small cell lung cancer which has spread beyond the lungs (extensive cancer) or come back after earlier treatment (recurrent cancer).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Combination Treatment | Experimental | Paclitaxel at 175 mg/m2 + Carboplatin at area under the curve (AUC) 5 on day 1. Then, Temozolomide at the doses described under "Interventions" from day 2 to day 6 (a total of 5 days). Cycle length is 21 days. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Combination Treatment - Cohort 1 | Drug | Paclitaxel at 175 mg/m2 intravenously + Carboplatin at AUC 5 intravenously on day 1. Temozolomide at 75 mg/m2 per day from day 2 to day 6. |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Tolerated Dose of Temozolomide in Combination with Fixed Doses of Paclitaxel and Carboplatin | Temozolomide was administered at different dose levels (see Cohorts 1-4) until the maximum tolerated dose (MTD) was reached. MTD is the dose at which 0/6 or 1/6 patients in the cohort experience dose limiting toxicity (DLT) during the first 4 week cycle with the next higher dose having at least 2/3 or 2/6 patients experiencing DLT. DLT will have occurred when the patient has 1 or more Grade 4 hematologic or nonhematologic toxicities. A DLT must occur in the first cycle of the combination and must be at least possibly attributed to the treatment regimen. Toxicities will be graded according to the NCI CTCAE Version 3.0. | 4 months |
| Measure | Description | Time Frame |
|---|---|---|
| Tumor response rate | Tumor response is evaluated according to Response Evaluation Criteria In Solid Tumors (RECIST) version 1.0 as determined by the investigator. Complete response (CR): Disappearance of all evidence of target and non-target lesions. Partial response (P): >= 30% reduction from baseline in the sum of the longest diameter of all lesions. CR and PR criteria should be met again after 4 weeks and before 6 weeks after initial assessment. Stable Disease (SD): Neither sufficient increase to qualify for PD nor sufficient shrinkage to qualify for PR. Progressive disease (PD) for target lesions: >= 20% increase in the sum of diameters of the target lesions taking as reference the smallest sum on study, and an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered . PD for non-target lesions is defined as unequivocal appearance of one or more new malignant lesions or unequivocal progression of existing non-target lesions. |
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Inclusion Criteria:
Age greater than or equal to 18 years
Karnofsky performance status (KPS) of greater than or equal to 70 (Appendix B)
Laboratory values (performed within 14 days prior to study drug administration, inclusive).
A life expectancy of greater than 12 weeks
Subjects must give written informed consent.
Biopsy proven small cell lung cancer.
CT of chest, abdomen, pelvis and MRI of head
Patients with brain metastases should be asymptomatic to enter the study
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Fa-Chyi Lee, MD | University of New Mexico | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of New Mexico Cancer Center | Albuquerque | New Mexico | 87106 | United States |
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| ID | Term |
|---|---|
| D008171 | Lung Diseases |
| D009369 | Neoplasms |
| ID | Term |
|---|---|
| D012140 | Respiratory Tract Diseases |
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| ID | Term |
|---|---|
| D016190 | Carboplatin |
| D017239 | Paclitaxel |
| D000077204 | Temozolomide |
| ID | Term |
|---|---|
| D056831 | Coordination Complexes |
| D009930 | Organic Chemicals |
| D043823 | Taxoids |
| D043822 | Cyclodecanes |
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| Combination Treatment - Cohort 2 | Drug | Paclitaxel at 175 mg/m2 intravenously + Carboplatin at AUC 5 intravenously on day 1. Temozolomide at 100 mg/m2 per day from day 2 to day 6. |
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| Combination Treatment - Cohort 3 | Drug | Paclitaxel at 175 mg/m2 intravenously + Carboplatin at AUC 5 intravenously on day 1. Temozolomide at 125 mg/m2 per day from day 2 to day 6. |
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| Combination Treatment - Cohort 4 | Drug | Paclitaxel at 175 mg/m2 intravenously + Carboplatin at AUC 5 intravenously on day 1. Temozolomide at 150 mg/m2 per day from day 2 to day 6. |
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| 7 months |
| D003516 |
| Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D004224 | Diterpenes |
| D013729 | Terpenes |
| D003606 | Dacarbazine |
| D014226 | Triazenes |
| D007093 | Imidazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |