Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Active	13 to 70	Other	DM03-0218 NCT00505635

Trial Description

Summary

PRIMARY OBJECTIVES:

• To determine time to progression (TTP).

SECONDARY OBJECTIVES:

• To determine the response rate and survival.

• To determine the effectiveness in delaying the appearance of Central Nervous System (CNS) disease.

• To evaluate the toxicity and effect on quality of life.

Further Study Information

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 (Temodar) 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.

Before treatment starts, you will have a complete medical history and physical exam, including routine blood tests (1-2 tablespoons). You will have a brain MRI, body CT scans, an EKG (test to measure the electrical activity of the heart), and an echocardiogram. If your heart rate is less than 50, you will be excluded from the protocol. Lung function tests will also be done when appropriate. Women who are able to have children must have a negative urine or blood pregnancy test.

Before starting each course of treatment, you will have a medical history and a physical exam, including blood tests (1-2 tablespoons). You will also have at least one chest x-ray.

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 to 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 the 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 CT scans and 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.

THIS IS AN INVESTIGATIONAL STUDY. The drugs used in this study are approved by the FDA. However, their use together in this study is investigational.

A total of 60 patients will take part in this study. All will be enrolled at UTMDACC.

Eligibility Criteria

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 RECIST criteria.

3. Patients between 13 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 ECOG performance status of 0, 1 or 2 will be eligible (Appendix B).

4. They should have normal blood counts with a 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 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 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.

Trial Contact Information

Trial Lead Organizations/Sponsors

M. D. Anderson Cancer Center at University of Texas

Nicholas E. Papadopoulos, MD

Principal Investigator

Nicholas E. Papadopoulos, MD

Ph: 713-792-2921

U.S.A.
Texas
	Houston
	M. D. Anderson Cancer Center at University of Texas
		Nicholas E. Papadopoulos	Principal Investigator

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00505635
Information obtained from ClinicalTrials.gov on March 18, 2009