RATIONALE: Drugs used in chemotherapy, such as paclitaxel albumin-stabilized nanoparticle formulation, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Pemetrexed may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving paclitaxel albumin-stabilized nanoparticle formulation together with pemetrexed may kill more tumor cells. PURPOSE: This phase I/II trial is studying the side effects and best dose of paclitaxel albumin-stabilized nanoparticle formulation when given together with pemetrexed and to see how well they work in treating patients with advanced non-small cell lung cancer, breast cancer, or other solid tumors.
OBJECTIVES: Primary * Determine the safety of paclitaxel albumin-stabilized nanoparticle formulation when administered with pemetrexed disodium in patients with advanced non-small cell lung cancer, breast cancer, or other solid tumors. (Phase I) * Determine the efficacy of this regimen, as measured by objective tumor response rate (RECIST criteria), in these patients. (Phase II) Secondary * Determine the preliminary efficacy of paclitaxel albumin-stabilized nanoparticle formulation and pemetrexed disodium in these patients. (Phase I) * Determine the overall survival of patients treated with this regimen. (Phase II) * Evaluate the frequency and severity of toxicities associated with this regimen. (Phase II) OUTLINE: This is a phase I, dose-escalation study of paclitaxel albumin-stabilized nanoparticle formulation followed by an open-label, phase II study. * Phase I: Patients receive pemetrexed disodium IV over 10 minutes and paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of paclitaxel albumin-stabilized nanoparticle formulation until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. * Phase II: Patients receive pemetrexed disodium and paclitaxel albumin-stabilized nanoparticle formulation at the MTD as in phase I. After completion of study treatment, patients are followed periodically.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
49
University of California Davis Cancer Center
Sacramento, California, United States
Number of Participants With Dose Limiting Toxicities
Dose limiting toxicity (DLT) was defined as any of the following occurring during the first cycle: Grade 4 thrombocytopenia, or grade 3 thrombocytopenia associated with bleeding, requirement for transfusion, febrile neutropenia, neutropenia with documented infection. Non-hematologic DLT included any other ≥ grade 3 non-hematologic toxicity that was clinically significant and considered by the investigator to be related to study drug. Alopecia and grade 3 allergic reaction/hypersensitivity with infusion were not considered DLTs.
Time frame: Up to21 days
Number of Patients With Toxicities
Toxicities was evaluated based on the standard NCI CTCAE Version 3.0 grading criteria. Attributable grade ≥ 3 hematologic and non-hematologic toxicities are presented here.
Time frame: Up to 1 year
Duration of Overall Survival
From time of enrollment to the first observation of disease progression or death.
Time frame: Up to 2 years
Number of Participants With Complete Response
Per RECIST criteria, complete response (CR) is defined as the disappearance of all target lesions.
Time frame: Up to 2 years
Number of Participants With Stable Disease
Stable Disease is measured from the start of the treatment until the criteria for disease progression are met. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Time frame: Up to 2 years
Number of Participants With Partial Response
At least a 30% decrease in the sum of the longest diameter of target lesions
Time frame: Up to 2 years
Number of Participants With Disease Control
Disease control is complete response plus partial response plus stable disease from the start of treatment to death or disease progression.
Time frame: Up to 2 years
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