Metastatic Melanoma
Conditions
Keywords
Metronomic Therapy, Metastatic Melanoma, Vinblastine, Cyclophosphamide, Dacarbazine
Brief summary
SUMMARY: Metronomic Therapy in Patients with Metastatic Melanoma: A Phase II Study of Low Dose Vinblastine, Cyclophosphamide, and Dacarbazine. Patients with measurable metastatic melanoma are eligible. All patients will be treated as outlined below with combined vinblastine, cyclophosphamide, and dacarbazine. Patients will be treated continuously, until evidence of progression of disease, or for up to two cycles following disappearance of all disease. A cycle will be defined as three weeks of continuous therapy with a one week rest.
Detailed description
Low dose continuous chemotherapy, called metronomic chemotherapy, is designed to target vascular cells and inhibit tumor growth and metastasises. A recent study in a melanoma mouse model has identified low dose vinblastine, cyclophosphamide and dacarbazine as a treatment which improves the animal's survival and is superior to full dose dacarbazine alone. This clinical trial seeks to translate this laboratory model directly into metastatic melanoma patients.
Interventions
DRUGvinblastine
1 mg/m2 vinblastine given three times per week administered intravenously.
DRUGCyclophosphamide
60 mg/m2 cyclophosphamide taken orally every day for 3 weeks with one week rest
DRUGdacarbazine
15 mg/m2 dacarbazine given three times per week for 3 weeks with 1 week rest
Sponsors
Dartmouth-Hitchcock Medical Center
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
* Metastatic melanoma with measurable disease * Patients must be at least 4 weeks from their last immunotherapy, radiation, surgery or chemotherapy (6 weeks for nitrosoureas) and recovered from all ill * Karnofsky Performance Status ≥60% * Life expectancy ≥ twelve weeks * Adequate end organ function * Women should not be lactating and, if of childbearing age, have a negative pregnancy test within two weeks of entry to the study. * Appropriate Contraception in both sexes * The patient must be competent and signed informed consent.
Exclusion criteria
* Concomitant second malignancy except for non-melanoma skin cancer, and non-invasive cancer such as cervical CIS, superficial bladder cancer without local recurrence, breast CIS. * In patients with a prior history of invasive malignancy, less than five years in complete remission. * Have evidence of significant co-morbid illness such as uncontrolled diabetes - Uncontrolled brain metastasis: Patients with brain metastasis most have been treated with brain radiation therapy or surgery and remain clinically stable for a minimum of 4 weeks.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival | From date of registration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months | Tumor evaluation will be performed every 8 weeks from day 1 of cycle 1 (+/- 1 week) while on therapy assessed by RECIST 1.0 criteria. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Response Rate | Tumor evaluation will be performed every 8 weeks from day1 of cycle 1 (+ 1 week) while on therapy, clinical response will be assessed no less than 4 weeks after response criteria met. | To be assigned a status of partial response or complete response, changes in tumor measurements must be confirmed by repeat assessments that should be performed no less than 4 weeks after the criteria for response are first met. In the case of stable disease, follow-up measurements must have met the stable disease criteria at least once after study entry at a minimum interval (in general, not less than 6-8 weeks) that is defined in the study protocol |
Countries
United States
Participant flow
Recruitment details
Enrolled from 6/2010 to 11/2012 at Dartmouth Hitichcock
Participants by arm
| Arm | Count |
|---|---|
| Combined Low Dose Treatment A cycle of therapy is 3 weeks of continuous dosing with a 1 week rest.
Schema of treatment is:
1 mg/m2 vinblastine three times a week iv 60 mg/m2 cyclophosphamide by mouth 15 mg/m2 dacarbazine three times a week iv
vinblastine: 1 mg/m2 vinblastine given three times per week administered intravenously.
Cyclophosphamide: 60 mg/m2 cyclophosphamide taken orally every day for 3 weeks with one week rest
dacarbazine: 15 mg/m2 dacarbazine given three times per week for 3 weeks with 1 week rest | 7 |
| Total | 7 |
Baseline characteristics
| Characteristic | Combined Low Dose Treatment |
|---|---|
| Age, Continuous | 65 years |
| Region of Enrollment United States | 7 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 7 |
| other Total, other adverse events | 5 / 7 |
| serious Total, serious adverse events | 0 / 7 |
Outcome results
Primary
Progression Free Survival
Tumor evaluation will be performed every 8 weeks from day 1 of cycle 1 (+/- 1 week) while on therapy assessed by RECIST 1.0 criteria.
Time frame: From date of registration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Single Arm | Progression Free Survival | 3 weeks |
Secondary
Clinical Response Rate
To be assigned a status of partial response or complete response, changes in tumor measurements must be confirmed by repeat assessments that should be performed no less than 4 weeks after the criteria for response are first met. In the case of stable disease, follow-up measurements must have met the stable disease criteria at least once after study entry at a minimum interval (in general, not less than 6-8 weeks) that is defined in the study protocol
Time frame: Tumor evaluation will be performed every 8 weeks from day1 of cycle 1 (+ 1 week) while on therapy, clinical response will be assessed no less than 4 weeks after response criteria met.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Single Arm | Clinical Response Rate | Stable Disease | 2 Participants |
| Single Arm | Clinical Response Rate | Progressive Disease | 5 Participants |