Melanoma (Skin)
Conditions
Keywords
stage IV melanoma, recurrent melanoma
Brief summary
RATIONALE: Drugs used in chemotherapy, such as carboplatin and ABI-007, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. PURPOSE: This phase II trial is studying the side effects and how well giving carboplatin together with ABI-007 works in treating patients with stage IV melanoma that cannot be removed by surgery.
Detailed description
OBJECTIVES: Primary * Assess the safety and antitumor activity of carboplatin and paclitaxel albumin-stabilized nanoparticle formulation (ABI-007) in patients with unresectable stage IV melanoma who have not received prior chemotherapy for their metastatic disease. (Cohort 1) * Assess the safety and antitumor activity of this regimen in patients with unresectable stage IV melanoma who have received prior chemotherapy for their metastatic disease. (Cohort 2) Secondary * Describe the impact of this regimen on parameters of immune function and angiogenesis in these patients. OUTLINE: This is a multicenter study. Patients are stratified according to prior chemotherapy for metastatic disease (yes vs no). Patients receive paclitaxel albumin-stabilized nanoparticle formulation (ABI-007) IV over 30 minutes followed by carboplatin IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days for at least 8 courses in the absence of disease progression or unacceptable toxicity. Blood and tumor tissue samples are collected periodically to evaluate secreted protein acidic and rich in cysteine (SPARC) content of tumor tissue by immunohistochemistry and to explore the impact of therapy on immune homeostasis. Samples are also analyzed by immunoenzyme techniques for angiogenesis markers. After completion of study treatment, patients are followed periodically for up to 2 years. PROJECTED ACCRUAL: A total of 74 patients will be accrued for this study.
Interventions
DRUGcarboplatin
DRUGpaclitaxel albumin-stabilized nanoparticle formulation
Sponsors
Alliance for Clinical Trials in Oncology
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically or cytologically confirmed unresectable stage IV melanoma * Measurable disease * Must have formalin-fixed, paraffin-embedded tumor tissue available for secreted protein acidic and rich in cysteine (SPARC) analysis pre-treatment (Mayo Clinic patients must be willing to submit a repeat biopsy at time of tumor progression) * Brain metastases allowed provided they were previously treated with no progression for ≥ 3 months * Patients with known brain metastases may receive concurrent steroid treatment PATIENT CHARACTERISTICS: * ECOG performance status 0-2 * Life expectancy ≥ 3 months * Absolute neutrophil count ≥ 1,500/mm\^3 * Platelet count ≥ 100,000/mm\^3 * Hemoglobin ≥ 9 g/dL (may be transfused to meet this requirement) * Creatinine ≤ 1.5 times upper limit of normal (ULN) * Total bilirubin ≤ 1.5 times ULN (elevated bilirubin allowed in patients with documented Gilbert's syndrome) * AST ≤ 2.5 times ULN * Alkaline phosphatase ≤ 2.5 times ULN * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during and for 1 month after completion of study therapy * No uncontrolled intercurrent illness including, but not limited to, the following: * Active infection * Congestive heart failure (New York Heart Association class III-IV heart disease) * No peripheral neuropathy ≥ grade 2 * No other malignancy within the past 5 years except basal cell or squamous cell carcinoma of the skin previously treated with local resection only or carcinoma in situ of the cervix PRIOR CONCURRENT THERAPY: * See Disease Characteristics * Recovered from prior therapy * At least 4 weeks since prior radiotherapy * At least 4 weeks since prior interferon or interleukin-2 * At least 4 weeks since prior chemotherapy (cohort 1 ) * No prior chemotherapy in the metastatic setting (cohort 2) * No prior treatment for melanoma with any of the following agents: * Platinum chemotherapy (e.g., carboplatin or cisplatin) * Taxanes (e.g., paclitaxel or docetaxel) * Paclitaxel albumin-stabilized nanoparticle formulation (ABI-007) * No other concurrent chemotherapy * No other concurrent investigational agents * No concurrent radiotherapy, including palliative radiotherapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Tumor Response Rate, as Measured by RECIST Criteria | Up to 2 years | The RECIST criteria will be used for response assessments. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. A confirmed tumor response is defined to be either a CR or PR noted as the objective status on 2 consecutive evaluations at least 4 weeks apart. The tumor response rate is defined as the total number of eligible patients who achieved a complete or partial response according to the RECIST criteria divided by the total number of eligible patients enrolled on study. All patients meeting the eligibility criteria who have signed a consent form and have begun treatment will be evaluable for response. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Survival Time | Up to 2 years | Survival time is defined as the time from registration to death due to any cause. The distribution of survival time will be estimated using the method of Kaplan-Meier. 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 to Disease Progression | Up to 2 years | Time-to-disease progression (TTP) is defined as the time from registration to documentation of disease progression. If a patient dies without a documentation of disease progression, the patient will be considered to have had tumor progression at the time of their death unless there is sufficient documented evidence to conclude no progression occurred prior to death. The distribution of time-to-progression will be estimated using the method of Kaplan-Meier. 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 Response | Up to 3 years | Duration of response is defined for all eligible patients who have achieved an objective response as the date at which the patient's objective status is first noted to be either a CR or PR to the date progression is documented. |
| Number of Treatment Cycles Administered | Up to 2 years | Number of treatment cycles administered is defined to be the number of treatment cycles administered until the patient is removed from treatment due to progression, toxicity, or refusal. 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 (Prior Chemotherapy, PT) Patients with malignant melanoma who have received prior chemotherapy for their metastatic disease receive 100 mg/m\^2 paclitaxel albumin-stabilized nanoparticle formulation (ABI-007) IV over 30 minutes followed by AUC 2 carboplatin IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days for at least 8 courses in the absence of disease progression or unacceptable toxicity. | 34 |
| Cohort 2 (Chemotherapy Naive, CN) For patients with malignant melanoma who have not received prior chemotherapy for their metastatic disease, patients receive 100 mg/m\^2 paclitaxel albumin-stabilized nanoparticle formulation (ABI-007) IV over 30 minutes followed by AUC 2 carboplatin IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days for at least 8 courses in the absence of disease progression or unacceptable toxicity. | 39 |
| Total | 73 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 2 |
Baseline characteristics
| Characteristic | Cohort 1 (Prior Chemotherapy, PT) | Cohort 2 (Chemotherapy Naive, CN) | Total |
|---|---|---|---|
| Age, Continuous | 60 years | 59 years | 59 years |
| Region of Enrollment United States | 34 participants | 39 participants | 73 participants |
| Sex: Female, Male Female | 11 Participants | 16 Participants | 27 Participants |
| Sex: Female, Male Male | 23 Participants | 23 Participants | 46 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 34 / 34 | 38 / 39 |
| serious Total, serious adverse events | 3 / 34 | 5 / 39 |
Outcome results
Primary
Tumor Response Rate, as Measured by RECIST Criteria
The RECIST criteria will be used for response assessments. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. A confirmed tumor response is defined to be either a CR or PR noted as the objective status on 2 consecutive evaluations at least 4 weeks apart. The tumor response rate is defined as the total number of eligible patients who achieved a complete or partial response according to the RECIST criteria divided by the total number of eligible patients enrolled on study. All patients meeting the eligibility criteria who have signed a consent form and have begun treatment will be evaluable for response.
Time frame: Up to 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 (Prior Chemotherapy, PT) | Tumor Response Rate, as Measured by RECIST Criteria | 8.8 percentage of participants |
| Cohort 2 (Chemotherapy Naive, CN) | Tumor Response Rate, as Measured by RECIST Criteria | 25.6 percentage of participants |
Secondary
Duration of Response
Duration of response is defined for all eligible patients who have achieved an objective response as the date at which the patient's objective status is first noted to be either a CR or PR to the date progression is documented.
Time frame: Up to 3 years
Population: Participants with Complete or Partial response, were analyzed
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 (Prior Chemotherapy, PT) | Duration of Response | 3.5 months |
| Cohort 2 (Chemotherapy Naive, CN) | Duration of Response | 12.1 months |
Secondary
Number of Treatment Cycles Administered
Number of treatment cycles administered is defined to be the number of treatment cycles administered until the patient is removed from treatment due to progression, toxicity, or refusal. 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 (MEDIAN) |
|---|---|---|
| Cohort 1 (Prior Chemotherapy, PT) | Number of Treatment Cycles Administered | 4 cycles |
| Cohort 2 (Chemotherapy Naive, CN) | Number of Treatment Cycles Administered | 4 cycles |
Secondary
Survival Time
Survival time is defined as the time from registration to death due to any cause. The distribution of survival time will be estimated using the method of Kaplan-Meier. 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 (MEDIAN) |
|---|---|---|
| Cohort 1 (Prior Chemotherapy, PT) | Survival Time | 10.9 months |
| Cohort 2 (Chemotherapy Naive, CN) | Survival Time | 11.1 months |
Secondary
Time to Disease Progression
Time-to-disease progression (TTP) is defined as the time from registration to documentation of disease progression. If a patient dies without a documentation of disease progression, the patient will be considered to have had tumor progression at the time of their death unless there is sufficient documented evidence to conclude no progression occurred prior to death. The distribution of time-to-progression will be estimated using the method of Kaplan-Meier. 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 (MEDIAN) |
|---|---|---|
| Cohort 1 (Prior Chemotherapy, PT) | Time to Disease Progression | 4.1 months |
| Cohort 2 (Chemotherapy Naive, CN) | Time to Disease Progression | 4.5 months |