Biochemotherapy With Temozolomide, Velban, Cisplatin, Interleukin-2, Interferon-alpha and Thalidomide for Metastatic Melanoma With Optional Intrathecal Interleukin-2 Treatment
18 Years
65 Years
Both
Melanoma
Trial Information
Biochemotherapy With Temozolomide, Velban, Cisplatin, Interleukin-2, Interferon-alpha and Thalidomide for Metastatic Melanoma With Optional Intrathecal Interleukin-2 Treatment
Some of the drugs in this study have been used with DTIC (Dacarbazine) in the past to
control Melanoma that has spread to other parts of the body. However, in most of those
cases, the duration of these results are limited and ineffective to control or prevent
spread of the disease into the brain, the membranes that cover the brain, the spinal cord,
and the nerve roots. In this study, temozolomide is being used instead of DTIC. Temodar
has been proven to be one of the most effective therapeutic agents to control malignancies
in the brain. Thalidomide is designed to decrease the formation of new blood vessels that
feed tumors.
The treatment plan for this study is divided in two parts. The first part of this study
(induction therapy) is done to try to get your disease under control. The second part of
this study (maintenance therapy) is to maintain or improve the results of the first part of
the treatment plan.
Induction Therapy:
Induction therapy includes three 5-day courses of treatment with thalidomide, temozolomide,
vinblastine, cisplatin, interleukin-2, and interferon-alpha. The courses are repeated in
cycles of three to four weeks depending on recovery from side effects from the previous
course of treatment.
All of the drugs that are given through a vein will be given through a catheter (plastic
tube) inserted in a vein in one of your arms or into the vein that runs underneath the
collar bone and threaded into the central vein in the upper part of the chest.
You will be admitted in the hospital on Day 0. You will start receiving liquids (hydration)
and be prepared to start temozolomide on day 1 of the admission. It is anticipated that you
will remain in the hospital for one week. Depending on degree of side effects a longer stay
in the hospital may be required.
Temozolomide will be given by mouth on the first day of the treatment every 4 hours for
three doses. A fourth dose may be considered with later courses of treatment if it is well
tolerated.
Vinblastine will be given through the catheter on Days 1,2,3 and 4 of the cycle. The
infusion should last between 15 to 30 minutes.
Cisplatin will be given through the catheter on Days 1,2,3 and 4 of the cycle. The infusion
should last between 45 to 120 minutes. Care will be given to fully hydrate the body to
decrease chances for kidney damage.
Thalidomide will be given by mouth once a day throughout the cycle of treatment. It is given
as a single dose starting on Day 0, the day before the start of the temozolomide, and then
every day for the entire cycle.
Interleukin-2 will be given as continuous infusion through the catheter over 24 hours for
four days in a row (over 96 hours). It will be given from Day 1 through Day 5 of the cycle.
Interferon alpha will be given as "an insulin-type injection" under the skin, into the fatty
tissue, once a day on Days 1,2,3,4 and 5 of each cycle
You will receive up to 3 courses of induction therapy. The courses will be repeated in
cycles of 3-4 weeks depending on adequate recovery from the side effects. If you have stable
disease or improved disease, you will go on to receive maintenance therapy.
Maintenance Therapy:
Long-term daily treatment with the study drugs will be given for six 4-week cycles.
Temozolomide will be given by mouth daily for 21 days (3 weeks). This will be followed by
one week without Temozolomide treatment. This makes up one cycle of treatment.
Interleukin-2 and interferon alpha will be given during the one week of rest from
temozolomide. This will require one week of hospitalization. Interleukin-2 is given as a
continuous infusion through the catheter over the first 5 days. The first day the dose will
be high and it will be decreased slowly to a lower dose on the last 3 days. The interferon
alpha will be given as an injection in the fatty tissues under the skin once a day for 5
days on the same days the interleukin-2 is given.
Thalidomide will be given by mouth once a day every day for the full 4-week cycle.
Supportive care with medications for fever, chills, nausea, vomiting, diarrhea, will be
given during treatment. You will also be given fluids with appropriate electrolytes to
replenish blood levels and to replenish blood volume to help the kidneys.
How you respond to treatment will be evaluated with computed tomography (CT) scans and
magnetic resonance images (MRIs) of the brain. This will occur after the second course and
third course of induction therapy and then after the third and sixth courses of maintenance
therapy and periodically until off study.
You will be requested to complete a questionnaire to evaluate your quality of life before
treatment starts, at the end of Cycles 2 and 3 of induction therapy, and at the end of
Cycles 3 and 6 of maintenance therapy.
You will be taken off study if the disease gets worse or intolerable side effects occur.
Should you be taken off study early, a long term follow-up will be requested.
For those patients who complete the treatment, radiographic evaluation with body CT scans
and brain MRI will be done. They will have physical exams, and blood tests (1 to 2
tablespoons per visit) every 3 months for the first year, every 4 months for the second
year, every 6 months up to the 5th year, and then once a year.
A total of 60 patients will take part in this study.
Inclusion Criteria:
1. Patients with histologically documented diagnosis of advanced stage IV or
unresectable stage III melanoma are eligible.
2. They should have recurrent melanoma with measureable or evaluable sites of disease in
order to assess the response to treatment by Response Evaluation Criteria In Solid
Tumors (RECIST) criteria.
3. Patients between 18 years of age and 65 years of age with an expected survival
greater than 8 weeks and a Karnofsky performance status of 50% or better or an
Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 will be
eligible.
4. They should have normal blood counts with a white blood count (WBC) count of more
than or equal to 3000/mm^3 an absolute neutrophil count of more than or equal to
1500/mm^3 and a platelet count of more than 100,000/mm^3 and have no impairment of
renal function (serum creatinine of less than 1.6 mg/dl), hepatic function (serum
bilirubin level of < 1.2 mg/dl) and no evidence of significant cardiac or pulmonary
dysfunction.
5. They should have no significant intercurrent illness such as an active infection,
uncontrolled psychiatric illness, hypercalcemia (calcium > 11 mg), or active GI
bleeding.
6. They should not have been exposed to any previous chemotherapy or isolation perfusion
for malignant melanoma and have had no previous exposure to interleukin-2. Prior
adjuvant interferon is permitted. Prior radiation therapy for metastatic melanoma is
permitted provided the patient has un-irradiated metastatic sites for response
evaluation and has fully recovered from its toxicity.
Exclusion Criteria:
1. Patients with brain and/or bone metastases only.
2. Patients with symptomatic central nervous system involvement by melanoma either as
brain metastasis by MRI or spinal cord compression. Patients with brain metastases
are not eligible unless their disease can be resected, it is asymptomatic, not
associated with cerebral edema, or they are clinically stable after radiation and off
corticosteroid therapy for 4 weeks. No major surgery or RT within 21 days before
starting of treatment.
3. Patients with significant cardiac illness such as symptomatic coronary artery disease
or previous history of myocardial infarction, impaired left ventricle function (EF
<55%) on account of any organic disease such as hypertension or valvular heart
disease or serious cardiac arrhythmia requiring therapy. Patients with an
electrocardiogram (EKG) disclosing an absolute QT interval >460 msec in the presence
of serum potassium >/=4.0 mEq/L and magnesium >/= 1.8 mg/dL. Patients with heart rate
less than 50.
4. Patients with significant impairment of pulmonary function on account of chronic
bronchitis or chronic obstructive pulmonary disease (COPD) which has resulted in
impairment of vital capacity of Left Ventricular Ejection Fraction (FE VI) to <75% of
predicted normal values.
5. Patients with symptomatic effusions on account of pleural, pericardial or peritoneal
metastases of melanoma.
6. Patients who are unable to stay in Houston to receive therapy (first cycle) and be
able to return for follow-up visits as required by this study.
7. Patients with a history of second malignant tumor, other than the common skin cancers
- basal and squamous carcinomas, within the past 5 years and uncertainty about the
histological nature of the metastatic lesions.
8. Patients with history of deep vein thrombi (DVT) or pulmonary embolism (PE) are
excluded.
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Time to Progression (TTP)
Outcome Description:
TTP defined as the time from date of first dose of study medication to first documentation of objective tumor progression in days. Response evaluation by Response Evaluation Criteria in Solid Tumors (RECIST) done following 2 cycles and 3 cycles.
Outcome Time Frame:
Following two 21 day cycles until disease progression
Safety Issue:
No
Principal Investigator
Nicholas E. Papadopoulos, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
M.D. Anderson Cancer Center
Authority:
United States: Institutional Review Board
Study ID:
DM03-0218
NCT ID:
NCT00505635
Start Date:
March 2007
Completion Date:
April 2010
Related Keywords:
- Melanoma
- advanced stage IV melanoma
- unresectable stage III melanoma
- Melanoma
- Temozolomide
- Velban
- Vinblastine
- Cisplatin
- Interleukin-2
- Intron-A
- Interferon Alpha-2b
- Thalidomide
- Thalomid
- Temodar
- Proleukin
- Melanoma
Name | Location |
|---|---|
| U.T.M.D. Anderson Cancer Center | Houston, Texas 77030 |
