Breast Cancer, Lung Cancer, Unspecified Adult Solid Tumor, Protocol Specific
Conditions
Keywords
male breast cancer, recurrent breast cancer, stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer, stage IV breast cancer, stage IIIA non-small cell lung cancer, stage IIIB non-small cell lung cancer, stage IV non-small cell lung cancer, recurrent non-small cell lung cancer, unspecified adult solid tumor, protocol specific
Brief summary
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.
Detailed description
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.
Interventions
DRUGAbraxane
ABI-007 IV administration following pemetrexed on Day 1 of each cycle (infused over 30 minutes)
DRUGAlimta
Pemetrexed IV administration on Day 1 of each cycle (infused over 10 minutes)
Sponsors
Celgene
Eli Lilly and Company
University of California, Davis
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. For the phase II portion patients must have cytologically or histologically proven selected stage IIIB (pleural effusion) or IV NSCLC. 2. For the phase II portion patients must have NSCLC that has progressed or recurred after treatment with platinum-based therapy. 3. No prior pemetrexed. Prior Taxol is allowed. Prior ABI 007 is not allowed. 4. Patients must have measurable disease by RECIST criteria for the phase II portion. 5. Patients must be 18 years of age or older. 6. Patients must have a performance status of 0 -2 7. Patients must have an estimated survival of at least 3 months. 8. Any prior chemotherapy must have been completed at least 4 weeks prior to start of treatment. 9. Patients must have adequate renal function as documented by a calculated creatinine clearance of \> 45 ml/min 10. Patients must have adequate liver functions: AST and ALT \< 2.5 X upper limit of normal, and bilirubin \< upper limit of normal. 11. Patients must have adequate bone marrow function: Platelets \>100,000 cells/mm3 and ANC \> 1,500 cells/mm3. 12. For patients who have baseline clinically significant pleural or peritoneal effusions (on the basis of symptoms or clinical examination) before initiation of pemetrexed therapy, consideration should be given to draining the effusion prior to dosing. 13. Patients with asymptomatic treated brain metastasis (surgical resection or radiotherapy) may be included if they are neurologically stable and have been off steroids and anticonvulsants for at least 4 weeks. 14. Patients must be able to take and retain oral medication. 15. Ability to take folic acid, vitamin B12 and dexamethasone according to protocol. 16. Ability to interrupt NSAIDS 2 days before, the day of, and 2 days following administration of pemetrexed. 17. Patients of reproductive potential must agree to use effective contraceptive method while on treatment and for 3 months afterwards as the effects of these drugs on the unborn fetus are unknown. 18. No other current active malignancy. 19. Patient or his/her legally authorized representative or guardian signed the Informed Consent form prior to participation in any study-related activities.
Exclusion criteria
1. Pregnant or breastfeeding women. 2. Patient with pre-existing peripheral neuropathy of NCI CTCAE Version 3.0 of grade 2. 3. Patient has a clinically significant concurrent illness. 4. Patient is currently enrolled in a different clinical study in which investigational procedures are performed or investigational therapies are administered. 5. Patient has a history of allergy or hypersensitivity to the study drugs or a taxane. 6. Patient has serious medical risk factors involving any of the major organ systems such that the investigator considers it unsafe for the patient to receive an experimental research drug. 7. Prior therapy with pemetrexed, or ABI-007. 8. Patient is receiving treatment with any excluded concomitant medication. 9. Presence of third space fluid which cannot be controlled by drainage.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Dose Limiting Toxicities | Up to21 days | 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. |
| Number of Patients With Toxicities | Up to 1 year | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Stable Disease | Up to 2 years | 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 |
| Duration of Overall Survival | Up to 2 years | From time of enrollment to the first observation of disease progression or death. |
| Number of Participants With Disease Control | Up to 2 years | Disease control is complete response plus partial response plus stable disease from the start of treatment to death or disease progression. |
| Number of Participants With Partial Response | Up to 2 years | At least a 30% decrease in the sum of the longest diameter of target lesions |
| Number of Participants With Complete Response | Up to 2 years | Per RECIST criteria, complete response (CR) is defined as the disappearance of all target lesions. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Phase I: Abraxane and Pemetrexed A 3 + 3 dose escalation design was used to determine the maximum tolerated dose and the recommended phase II dose. Alimta® (pemetrexed) 500 mg/m2 IV administration on Day 1 of each cycle with Abraxane® (ABI 007) 180 mg/m2, 220 mg/m2 and 260 mg/m2 IV administration following pemetrexed on Day 1 of each cycle . | 12 |
| Phase II: Abraxane and Pemetrexed Alimta® (pemetrexed) 500 mg/m2 IV administration on Day 1 of each cycle with Abraxane® (ABI 007) 260 mg/m2IV administration following pemetrexed on Day 1 of each cycle | 37 |
| Total | 49 |
Baseline characteristics
| Characteristic | Phase I: Abraxane and Pemetrexed | Phase II: Abraxane and Pemetrexed | Total |
|---|---|---|---|
| Age, Continuous | 70 years | 63 years | 63 years |
| Region of Enrollment United States | 12 Participants | 37 Participants | 49 Participants |
| Sex: Female, Male Female | 5 Participants | 14 Participants | 19 Participants |
| Sex: Female, Male Male | 7 Participants | 23 Participants | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 8 / 12 | 15 / 37 |
| serious Total, serious adverse events | 1 / 12 | 6 / 37 |
Outcome results
Primary
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
Population: At dose level 1, 2 and 3 three participants were treated with no dose limiting toxicities. Three additional participants were treated at dose level 3 with no dose limiting toxicities.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase I: Dose Level 1 | Number of Participants With Dose Limiting Toxicities | 0 participants |
| Phase I: Dose Level 2 | Number of Participants With Dose Limiting Toxicities | 0 participants |
| Phase I: Dose Level 3 | Number of Participants With Dose Limiting Toxicities | 0 participants |
Primary
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase I: Dose Level 1 | Number of Patients With Toxicities | 15 Participants |
Secondary
Duration of Overall Survival
From time of enrollment to the first observation of disease progression or death.
Time frame: Up to 2 years
Population: Of the 12 patients in the phase I component 10 were assessable for response. In the phase II component, 31 of 37 patients were evaluable for response.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Phase I: Dose Level 1 | Duration of Overall Survival | 13.5 months | Standard Error 0 |
| Phase I: Dose Level 2 | Duration of Overall Survival | 4.5 months | Standard Error 0 |
Secondary
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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase I: Dose Level 1 | Number of Participants With Complete Response | 0 participants |
| Phase I: Dose Level 2 | Number of Participants With Complete Response | 0 participants |
Secondary
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase I: Dose Level 1 | Number of Participants With Disease Control | 7 Participants |
| Phase I: Dose Level 2 | Number of Participants With Disease Control | 17 Participants |
Secondary
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase I: Dose Level 1 | Number of Participants With Partial Response | 0 Participants |
| Phase I: Dose Level 2 | Number of Participants With Partial Response | 5 Participants |
Secondary
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase I: Dose Level 1 | Number of Participants With Stable Disease | 7 Participants |
| Phase I: Dose Level 2 | Number of Participants With Stable Disease | 12 Participants |