Metastatic Melanoma
Conditions
Keywords
Metastatic Melanoma
Brief summary
This is a Phase II Evaluation of Docetaxel and Vinorelbine Plus Sargramostim in subjects who have metastatic melanoma which has advanced beyond the point at which local therapies such as surgery or radiation therapy would be helpful. Without effective treatment, metastatic melanoma is usually a severe and fatal disease. Chemotherapy agents or combinations of chemotherapy agents have produced tumor shrinkage in some patients, which has occasionally persisted. This research involves treatment with a combination of chemotherapy drugs known to be active against melanoma alone. The investigational purpose of this study is to determine if the combination of docetaxel, vinorelbine and sargramostim will produce a response (complete or partial) in metastasis melanoma. The researchers also wants to find out what side effects are associated with this combination of drugs.
Detailed description
Annually in the U.S. there is an estimated 40,000 new cases of malignant melanoma and 7000 deaths. This disease is becoming more common with its incidence increasing at a more rapid rate in the past decade than that of any other cancer except lung cancer in women. Metastatic disease responds poorly to the usual treatments with only 2 out of 30 drugs tested, DTIC and nitrosoureas, showing response rates greater than 10%. Complete responses are rare. Metastatic melanoma is a disease with few therapeutic options. Multi-agent chemotherapy with cisplatin (CDDP), Dacarbazine (DTIC), Carmustine (BCNU), with or without Tamoxifen, offers a 20% response rate but has failed to consistently demonstrate a significant improvement in overall survival (OS) or disease-free survival (DFS) when compared to a single agent DTIC. Recently, investigators, in an effort to combine the activity of biologic response modifiers with chemotherapy, have developed combination biochemotherapy for metastatic melanoma. Legha et al reported an overall objective response rate of 64% with a 5-day biochemotherapy regimen. O'Day et al reported similar results (overall response rate of 57%) using a modified 5-day biochemotherapy regimen. The above regimens all have significant toxicities and modest response rates. Clearly, more effective less toxic regimens are needed. Vinorelbine tartrate (Navelbine) and Docetaxel (Taxotere) have both shown activity against melanoma. Additionally, the combination of both drugs has shown enhanced activity against melanoma.
Interventions
DRUGVinorelbine
30 mg/m2 IV over 6-10 min every 14 days
DRUGDocetaxel
40mg/m2 IV over 1 hour every 14 days
DRUGSargramostim
250 mcg/m2 subcutaneous (SQ) daily (QD) x 10 days
Sponsors
Bayer
John P. Fruehauf
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
* Age greater than or equal to 18 * Karnofsky Performance Status (KFS) of greater than or equal to 70 * Laboratory values (performed in 14 days, inclusive prior to study drug administration): * Absolute neutrophil count (ANC) \>1500/mm3 * Platelet count \>100,000/mm3 * Hemoglobin \> 10 g/dl * Blood urea nitrogen (BUN) and serum creatinine \< 0.5 times the upper limit of laboratory normal * Total and direct bilirubin \< 1.5 times the upper limit of laboratory normal * Serum glutamic-oxaloacetic transaminase (SGOT) and Serum glutamic pyruvic transaminase(SGPT) \< 3 times the upper limit of laboratory normal * Alkaline phosphatase \< 3 times upper limit of laboratory normal * Life expectancy of greater than 12 weeks * Written informed consent
Exclusion criteria
* No recovery from all active toxicities of prior therapies * Surgery within 1 week prior to study drug administration, providing acute surgical toxicity is resolved * Subjects within acute infection treated with intravenous antibiotics * Frequent vomiting or medical condition that could interfere with oral medication intake (e.g., partial bowel obstruction) * Concurrent malignancies at other sites with the exception of surgically cured carcinoma in situ (CIS ) of the cervix, basal or squamous cell carcinoma of the skin, and prior malignancies which have not required anit-tumor treatment within the preceding 24 months * Known HIV-positivity or AIDS-related illness * Women of childbearing potential who are not using an effective method of contraception (eligible patients must have a negative urine pregnancy test 24 hours prior to administration of study drug and be practicing medically approved contraceptive precautions) * Men who do not use an effective method of contraception. * Chemotherapy within four weeks prior to study drug administration or biologic therapy/immunotherapy within two weeks prior to study drug administration * Completion of radiation therapy, interstitial brachytherapy, or radiosurgery within 4 weeks prior to study drug administration (patients with brain metastases from melanoma must have completed radiotherapy to the brain at least 3 weeks before study commences) * Bone metastases as sole reason for Stage IV disease * Karnofsky Performance Status of less than or equal to 60
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) in Patients With AJCC Stage IV Metastatic Melanoma Treated With Docetaxel and Vinorelbine as First-line or Post-first Line (Salvage) Systemic Therapy | Six months from initial treatment | The primary endpoint is to evaluate the six-month progression-free survival (PFS) in patients with AJCC stage IV metastatic melanoma treated with docetaxel and vinorelbine as first-line or post-first line (salvage) systemic therapy. Progressive disease is defined as any new lesion or a greater than or equal to 20% increase in the largest perpendicular diameter of the sum of the T-lesions identified on contrast enhanced CT or MRI scan. |
Secondary
| Measure | Time frame |
|---|---|
| Percentage of Patients Alive at One Year | 1 year |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Docetaxel and Vinorelbine Plus Sargramostim The DVS regimen consisted of docetaxel 40 mg/m2 IV over 1 hour, vinorelbine 30 mg/m2 IV over 6 to 10 minutes on day 1, every 14 days, and GM-CSF, 250 mg/m2 SC on days 2 to 12. Patients received a cycle of this regimen every two weeks. | 52 |
| Total | 52 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 3 |
| Overall Study | Disease progression, relapse during acti | 12 |
| Overall Study | Physician Decision | 1 |
Baseline characteristics
| Characteristic | Docetaxel and Vinorelbine Plus Sargramostim |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 18 Participants |
| Age, Categorical Between 18 and 65 years | 34 Participants |
| Age, Continuous | 62.0 years |
| Region of Enrollment United States | 52 Participants |
| Sex: Female, Male Female | 16 Participants |
| Sex: Female, Male Male | 36 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 15 / 52 |
| other Total, other adverse events | 42 / 52 |
| serious Total, serious adverse events | 6 / 52 |
Outcome results
Primary
Progression-free Survival (PFS) in Patients With AJCC Stage IV Metastatic Melanoma Treated With Docetaxel and Vinorelbine as First-line or Post-first Line (Salvage) Systemic Therapy
The primary endpoint is to evaluate the six-month progression-free survival (PFS) in patients with AJCC stage IV metastatic melanoma treated with docetaxel and vinorelbine as first-line or post-first line (salvage) systemic therapy. Progressive disease is defined as any new lesion or a greater than or equal to 20% increase in the largest perpendicular diameter of the sum of the T-lesions identified on contrast enhanced CT or MRI scan.
Time frame: Six months from initial treatment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Docetaxel and Vinorelbine Plus Sargramostim | Progression-free Survival (PFS) in Patients With AJCC Stage IV Metastatic Melanoma Treated With Docetaxel and Vinorelbine as First-line or Post-first Line (Salvage) Systemic Therapy | 134 days |
Secondary
Percentage of Patients Alive at One Year
Time frame: 1 year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Docetaxel and Vinorelbine Plus Sargramostim | Percentage of Patients Alive at One Year | 25 Participants |