Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Rare Diseases

Melanoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Analgesics

Temozolomide

Aldesleukin

Cisplatin

Thalidomide

Vinblastine

Interferons

Interleukin-2

Interferon-alpha

Interferon alpha-2

Antiviral Agents

Antineoplastic Agents, Alkylating

Alkylating Agents

Immunologic Factors

Analgesics, Non-Narcotic

Immunosuppressive Agents

Anti-Bacterial Agents

Angiogenesis Inhibitors

Growth Inhibitors

Tubulin Modulators

Antimitotic Agents

Temozolomide 250 mg/m\^2 every 4 hours Day 1; Biochemotherapy of Velban 1.5 mg/m\^2 intravenous (IV) Days 1-4; Cisplatin 20 mg/m\^2 IV Days 1-4; + Interleukin-2 9 MIU/m\^2 IV over 24 Hours for 4 Doses Days 1-4; Intron-A 5 mu/m\^2 subcutaneously daily Days 1-5; + Oral Thalidomide 400 mg daily.

250 mg/m\^2 By Mouth Every 4 Hours x 3 Doses On Day 1

1.5 mg/m\^2 By Vein Over 15-30 Minutes On Days 1-4

Velban

20 mg/m\^2 By Vein Over 45-120 Minutes On Days 1-4

9 MIU/m\^2 By Vein Over 24 Hours x 4 Doses On Days 1-4

5 mu/m\^2 Subcutaneously (Under the skin) Daily On Days 1-5

Intron-A

Nicholas E. Papadopoulos, MD

The goal of this clinical research study is to learn if treatment with Temodar (temozolomide), Velban (vinblastine), Cisplatin, Proleukin (interleukin-2), Intron-A (interferon alpha), and thalidomide can help to control melanoma that has spread to other parts of the body. The safety of this treatment will also be studied.

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.

Biochemotherapy With Temozolomide for Metastatic Melanoma

Biochemotherapy With Temozolomide, Velban, Cisplatin, Interleukin-2, Interferon-alpha and Thalidomide for Metastatic Melanoma With Optional Intrathecal Interleukin-2 Treatment

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. Progression is defined, using RECIST, as a measurable increase in the smallest dimension of any target or non-target lesion, or the appearance of new lesions, since baseline.

Response evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST).

M.D. Anderson Cancer Center

Biochemotherapy With Temozolomide

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

Nicholas E. Papadopoulos, MD / Professor

Time to Progression (TTP)

Number of Participants With Response

Overall Study

Symptoms and General Pathology

Disease Progression

Melanoma, Cutaneous Malignant

Paclitaxel

Albumin-Bound Paclitaxel

Ipilimumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Starting dose of ABI-007 is 150 mg/m2 administered by vein on days 1, 8, 15 every 28 days. Ipilimumab 3 mg/kg by vein over 90 minutes on day 1. Ipilimumab dose repeated every 21 days for a total of 4 doses. Every 2 months for 6 months, then every 3 months for up to 2 years, participant contacted by telephone. Each call should last about 5 minutes.

Starting dose of ABI-007 is 150 mg/m2 administered by vein on days 1, 8, 15 every 28 days. The cycle length for ABI-007 is 28 days.

ABI-007

3 mg/kg by vein over 90 minutes on day 1. Ipilimumab dose repeated every 21 days for a total of 4 doses.

Every 2 months for 6 months, then every 3 months for up to 2 years, participant contacted by telephone. Each call should last about 5 minutes.

Phone Call

Adi Diab, MD

The goal of this clinical research study is to learn if the combination of ipilimumab and ABI-007 (abraxane) can help to control metastatic melanoma. The safety of this drug combination will also be studied.

Ipilimumab is designed to increase the immune system's ability to fight cancer.

Abraxane is designed to stop cancer cells from making new DNA (the genetic material of cells). This may stop the cancer cells from dividing into new cells.

Study Drug Administration:

If you are found to be eligible to take part in this study, you will receive ABI-007 by vein over about 30 minutes on Days 1, 8, and 15 of each 28-day cycle. During the first 3 months that you receive abraxane, you will also receive ipilimumab. You will receive ipilimumab by vein over about 90 minutes. You will receive it 4 times, each time about 3 weeks apart.

You will be given standard drugs to help decrease the risk of side effects. You may ask the study staff for information about how the drugs are given and their risks.

Study Tests:

Every week, blood (about 1 teaspoon) will be drawn for routine tests.

Before each cycle of abraxane:

* Your performance status will be recorded.
* You will have a physical exam, including measurement of your weight and vital signs.
* Blood (about 1 teaspoon) will be drawn for routine tests.
* Blood (about 1 teaspoon) will be drawn for tests of the immune system (first 3 cycles only).
* You will be asked about any other drugs you may be taking and about any side effects you may be having.
* If you are able to become pregnant, you will have a blood (about 1 teaspoon) or urine pregnancy test.

Every 8 weeks (+/- 7 days), you will have a chest x-ray and CT scans or MRI scans performed to check the status of the disease.

Length of Study:

You may receive ipilimumab for up to 3 months. You may continue taking abraxane for as long as the doctor thinks it is in your best interest. You will no longer be able to take the study drugs if the disease gets worse or intolerable side effects occur.

If you stop receiving the study drugs for any reason, you will have an End-of-Treatment Visit.

End-of-Treatment Visit:

Within 14 days after you stop study treatment, you will come into the clinic for the End-of-Treatment Visit. At this visit, the following tests will be performed:

* You will have a physical exam, including measurement of your vital signs and weight.
* You will be asked about any other drugs you may be taking and any side effects you may be having.
* Blood (about 2 tablespoons) will be drawn for routine tests.
* If the study doctor thinks it is in your best interest, you will have a CT scan or MRI scan to check for side effects.

Every 2 months for 6 months, then every 3 months for up to 2 years, you will also be contacted by telephone or during a routine clinic visit to see how you are doing. If you are called, each call should last about 5 minutes.

This is an investigational study. Ipilimumab is FDA approved and commercially available for the treatment of metastatic melanoma. abraxane is FDA approved and commercially available for the treatment of metastatic breast cancer. It is investigational to use abraxane, either alone or in combination with ipilimumab, for the treatment of metastatic melanoma.

Up to 64 patients will take part in this study. All will be enrolled at MD Anderson.

Phase II Study of Abraxane Plus Ipilimumab in Patients With Metastatic Melanoma

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v 1.1) was used. Complete Response (CR)= Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm, no new lesions; Partial Response (PR)= At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Progression-free survival (PFS) is the time from random assignment in a clinical trial to disease progression or death from any cause.

Celgene

Starting dose of ABI-007 is 150 mg/m2 administered by vein on days 1, 8, 15 every 28 days. Ipilimumab 3 mg/kg by vein over 90 minutes on day 1. Ipilimumab dose repeated every 21 days for a total of 4 doses.

ABI-007 + Ipilimumab

Starting dose of ABI-007 is 150 mg/m2 administered by vein on days 1, 8, 15 every 28 days. Ipilimumab 3 mg/kg by vein over 90 minutes on day 1. Ipilimumab dose repeated every 21 days for a total of 4 doses. Every 2 months for 6 months, then every 3 months for up to 2 years, participant contacted by telephone. Each call should last about 5 minutes.

ABI-007: Starting dose of ABI-007 is 150 mg/m2 administered by vein on days 1, 8, 15 every 28 days. The cycle length for ABI-007 is 28 days.

Ipilimumab: 3 mg/kg by vein over 90 minutes on day 1. Ipilimumab dose repeated every 21 days for a total of 4 doses.

Phone Call: Every 2 months for 6 months, then every 3 months for up to 2 years, participant contacted by telephone. Each call should last about 5 minutes.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Biochemotherapy With Temozolomide for Metastatic Melanoma	NCT00505635	Melanoma	Temozolomide Velban Cisplatin Interleukin-2 Intron-A Thalidomide	18 Years - 65 Years	M.D. Anderson Cancer Center
Phase II Study of Abraxane Plus Ipilimumab in Patients With Metastatic Melanoma	NCT01827111	Melanoma	ABI-007 Ipilimumab Phone Call	12 Years - 70 Years	M.D. Anderson Cancer Center
Biochemotherapy With Temozolomide for Metastatic Melanoma	NCT00505635	Melanoma	Temozolomide Velban Cisplatin Interleukin-2 Intron-A Thalidomide	18 Years - 65 Years	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for advanced stage iv melanoma