Symptoms and General Pathology

All Conditions

Neoplasms

Rare Diseases

Recurrence

Glioblastoma

Disease Attributes

Astrocytoma

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Bevacizumab

Lomustine

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

* Bevacizumab:

  -- Bevacizumab will be administered at a dose of 10 mg/kg i.v. every 14 days per standard of care and the drug label. A cycle is defined as 28 days (1 month).
* FMISO PET Scan

  * FMISO will be intravenously injected at a dose of 3.7 MBq/kg (0.1 mCi/kg) (maximum 260 MBq, 7 mCi) in \< 15 mL. The IV will remain in place for injection of the gadolinium for the MRI scan. There will be one injection of FMISO in the PET protocol. Approximately 90 minutes after the injection, the PET scan will begin.
  * The PET scan will be approximately 60-75 minutes.
* MRI -- Each MRI will last 60-75 minutes versus 45 minutes for standard brain MRIs.

Bevacizumab + CCNU:

* Bevacizumab will be administered at a dose of 10 mg/kg i.v. every 14 days per standard of care and the drug label. A cycle is defined as 28 days (1 month).
* CCNU will be administered at a dose of 110 mg/m2 every 42 days per standard of care and the drug label. A cycle is defined as 28 days (1 month).

  -FMISO PET Scan
* FMISO will be intravenously injected at a dose of 3.7 MBq/kg (0.1 mCi/kg) (maximum 260 MBq, 7 mCi) in \< 15 mL. The IV will remain in place for injection of the gadolinium for the MRI scan. There will be one injection of FMISO in the PET protocol. Approximately 90 minutes after the injection, the PET scan will begin.
* The PET scan will be approximately 60-75 minutes.

  - MRI
* Each MRI will last 60-75 minutes versus 45 minutes for standard brain MRIs.

FMISO PET

MR scans will be performed with the same sequences and in the same order during each visit, including T1- and T2-weighted volumetric images, fluid attenuated inversion recovery (FLAIR), contrast agent enhanced T1-weighted permeability, diffusion tensor imaging (DTI), T2/T2\*-weighted perfusion scans, and MR Spectroscopy. The "Autoalign" package available from the manufacturer will be used to achieve the same slice prescription in the same patient at each visit. Each MRI will last 60-75 minutes versus 45 minutes for standard brain MRIs.

A cycle is defined as 28 days (1 month). The study duration is 12 months (12 cycles). Patients will be treated after 12 months or at the time of progression per discretion of their responsible physician.

CCNU

Elizabeth Gerstner, MD

In this research study, the investigators are using FMISO-PET and MRI scans to explore the delivery of bevacizumab to the blood vessels in patient's with recurrent glioblastoma before and after treatment.

Bevacizumab is approved by the U.S. Food and Drug Administration for use in patients with recurrent glioblastoma . It works by targeting a specific protein called VEGF, which plays a role in promoting the growth or spreading of tumor blood vessels. Since anti-VEGF agents also affect normal blood vessels in the brain, they can inhibit the way other drugs used in combination with bevacizumab are delivered to the tumor.

In PET scans, a radioactive substance is injected into the body. The scanning machine finds the radioactive substance, which tends to go to cancer cells. For the PET scans in this research study, the investigators are using an investigational radioactive substance called FMISO. "Investigational" means that the role of FMISO-PET scans is still being studied and that research doctors are trying to find out more about it. FMISO goes to areas with low oxygenation so parts of the tumor that do not have enough oxygen can be seen.

In addition, a vascular MRI will be used to evaluate the changes in tumor blood flow, blood volume, and how receptive blood vessels are. This scan will be performed at the same time of the FMISO-PET scan.

This study does not add any additional treatment to patients with malignant glioma who are already scheduled to receive bevacizumab monotherapy. All treatment decisions will be at the discretion of the treating physician. There will be no change in the diagnosis or management of the patient based on any procedures or tests carried out as a part of this study.

If the participant chooses to take part in this research study each treatment cycle will last 28 days.

* Day 1-The participant will have the following procedures done before they can receive bevacizumab:

  * An assessment of the participant's tumor by Vascular MRI (Magnetic Resonance Imaging) and FMISO-PET scans
  * Blood pregnancy test for women of childbearing potential.
* Day 14:The participant will have the following procedures done after they receive bevacizumab:

  * An assessment of the participant's tumor by Vascular MRI (Magnetic Resonance Imaging) and FMISO-PET scans before the participant have received bevacizumab
  * Blood pregnancy test for women of childbearing potential.
* Day 28: The participant will have the following procedures done after they receive bevacizumab:

  * An assessment of the participant's tumor by Vascular MRI (Magnetic Resonance Imaging) and FMISO-PET scans after the participant has received bevacizumab
  * Blood pregnancy test for women of childbearing potential.

FMISO-PET Scans:

* The participant will have the scans performed in Charlestown, MA at the Martinos Center. The participant will be injected with two separate intravenous (IV) injections (listed below). Intravenous means a need will be injected into a vein in the participant's arm.

  * FMISO for PET scan and a contrast dye for the MRI scan
  * Drawing blood to assess the radioactivity of FMISO
* The PET scan will take approximately 60-75 minutes. The participant will receive one injection of FMISO. Following the injection of the radiotracer, blood samples will be taken from the second IV line. The tracer is given through a vein (IV) and travels through the participant's blood and collects in organs and tissues. The participant will need to wait nearby as the tracer is absorbed by the their body. This takes about 90 minutes. Then, the participant will lie on a narrow table that slides into a large tunnel-shaped scanner. The PET will pick up signals from the tracer and a computer will change the signals into 3D pictures that will be displayed on a monitor for the participant's study doctor to read.

MRI Scan:

* MRI scans will last about 60-75 minutes. This will occur at the same time as the PET scan. The participant will be injected with contrast dye twice during the MRI scan. The participant will have 3 MRI scans (prior to starting treatment, day 1 of treatment and day 14 of treatment) that would not have routinely been performed if the participant were not participating in this study.
* Blood samples will be collected during both scans in order to measure how the participant blood vessels are processing the radiotracer FMISO and how well it is being delivered to the tumor tissue.
* The participant will be assessed for side effects via clinic visit or phone call about 24 hours after each of the visits above.

Planned Follow-up: The investigators would like to call the participant every 3 months for three years after the 28 day visit to see how they are doing and if the participant is experiencing any side effects. If the participant is removed from the study due to an unacceptable side effect, the participant will be followed until it has been resolved.

FMISO PET Study of Glioblastoma

A Study to Evaluate Vascular Normalization in Patients With Recurrent Glioblastoma Treated With Bevacizumab Using FMISO PET and Vascular MRI

In this research study, the investigators are using FMISO-PET and MRI scans to explore the delivery of bevacizumab to the blood vessels in patient's with recurrent glioblastoma before and after treatment.

In this research study, the investigators are using FMISO-PET and MRI scans to explore the delivery of bevacizumab to the blood vessels in patient's with recurrent glioblastoma before and after treatment. Regional hypoxic volume (HV) was determined by thresholding the ratio of the standardized uptake values (SUV) of FMISO in the brain to cerebellum above 1.2. Since some patients had multiple tumors, we identified the HV region within the union of each contrast enhancing region of interest (ROI) and its surrounding FLAIR ROI, so individual tumors could be evaluated separately. HV represents the magnitude of hypoxia within each tumor.

The DCE-MRI data were processed using in-house custom software written in MATLAB to obtain maps of Ktrans based on the 2-parameter Tofts model. Population-level arterial input functions (AIFs) were used for DCE analysis; DCE was used only to calculate Ktrans. Median tumor values for Ktrans were calculated from the contrast enhancing region of interest (ROI). Higher value is more permeability.

This outcome measure looks at what blood flow was doing in tumor regions that were hypoxic. This outcome measured blood flow to the tumor using an MRI technique called dynamic susceptibility contrast enhancement that measures how fast injected contrast material flows through the tumor. This outcome specifically explored how blood flow to the tumor influenced tumor hypoxia.

National Cancer Institute (NCI)

Massachusetts General Hospital

Principal Investigator

Adverse event data was systematically assessed by regular investigator assessment and laboratory testing. Protocol only collected adverse events related to FMISO-PET scan, within 24 hrs (+/- 6 hrs) post-scan.

Bevacizumab:

* Bevacizumab will be administered at a dose of 10 mg/kg i.v. every 14 days per standard of care and the drug label. A cycle is defined as 28 days (1 month).

  -FMISO PET Scan
* FMISO will be intravenously injected at a dose of 3.7 MBq/kg (0.1 mCi/kg) (maximum 260 MBq, 7 mCi) in \< 15 mL. The IV will remain in place for injection of the gadolinium for the MRI scan. There will be one injection of FMISO in the PET protocol. Approximately 90 minutes after the injection, the PET scan will begin.
* The PET scan will be approximately 60-75 minutes.

  -MRI
* Each MRI will last 60-75 minutes versus 45 minutes for standard brain MRIs.

FMISO PET

MRI: MR scans will be performed with the same sequences and in the same order during each visit, including T1- and T2-weighted volumetric images, fluid attenuated inversion recovery (FLAIR), contrast agent enhanced T1-weighted permeability, diffusion tensor imaging (DTI), T2/T2\*-weighted perfusion scans, and MR Spectroscopy. The "Autoalign" package available from the manufacturer will be used to achieve the same slice prescription in the same patient at each visit. Each MRI will last 60-75 minutes versus 45 minutes for standard brain MRIs.

Bevacizumab: A cycle is defined as 28 days (1 month). The study duration is 12 months (12 cycles). Patients will be treated after 12 months or at the time of progression per discretion of their responsible physician.

FMISO PET & MRI Group 1

Bevacizumab + CCNU:

* Bevacizumab administered at dose of 10 mg/kg IV every 14 days per standard of care and drug label. Cycle defined as 28 days (1 month). Patients will be treated after 12 months or at the time of progression per discretion of their responsible physician.
* CCNU administered at dose of 110 mg/m2 every 42 days per standard of care and drug label. Cycle defined as 28 days (1 month). Patients will be treated after 12 months or at the time of progression per discretion of their responsible physician.

  -FMISO PET Scan
* FMISO intravenously injected at dose of 3.7 MBq/kg (0.1 mCi/kg) (maximum 260 MBq, 7 mCi) in \< 15 mL. IV will remain in place for injection of gadolinium for MRI scan. One injection of FMISO in PET protocol. Approximately 90 min after injection, PET scan will begin.
* PET scan will be approximately 60-75 minutes

  - MRI
* Each MRI will last 60-75 minutes vs 45 minutes for standard brain MRIs.

FMISO PET

MRI: MR scans will be performed with the same sequences and in the same order during each visit, including T1- and T2-weighted volumetric images, fluid attenuated inversion recovery (FLAIR), contrast agent enhanced T1-weighted permeability, diffusion tensor imaging (DTI), T2/T2\*-weighted perfusion scans, and MR Spectroscopy. The "Autoalign" package available from the manufacturer will be used to achieve the same slice prescription in the same patient at each visit. Each MRI will last 60-75 minutes vs 45 minutes for standard brain MRIs.

FMISO PET & MRI Group 2

Bevacizumab:

* Bevacizumab will be administered at a dose of 10 mg/kg i.v. every 14 days per standard of care and the drug label. A cycle is defined as 28 days (1 month).

  -FMISO PET Scan
* FMISO will be intravenously injected at a dose of 3.7 MBq/kg (0.1 mCi/kg) (maximum 260 MBq, 7 mCi) in \< 15 mL. The IV will remain in place for injection of the gadolinium for the MRI scan. There will be one injection of FMISO in the PET protocol. Approximately 90 minutes after the injection, the PET scan will begin.
* The PET scan will be approximately 60-75 minutes.

  - MRI
* Each MRI will last 60-75 minutes versus 45 minutes for standard brain MRIs.

FMISO PET

MRI: MR scans will be performed with the same sequences and in the same order during each visit, including T1- and T2-weighted volumetric images, fluid attenuated inversion recovery (FLAIR), contrast agent enhanced T1-weighted permeability, diffusion tensor imaging (DTI), T2/T2\*-weighted perfusion scans, and MR Spectroscopy. The "Autoalign" package available from the manufacturer will be used to achieve the same slice prescription in the same patient at each visit. Each MRI will last 60-75 minutes versus 45 minutes for standard brain MRIs.

Bevacizumab: A cycle is defined as 28 days (1 month). The study duration is 12 months (12 cycles). Patients will be treated after 12 months or at the time of progression per discretion of their responsible physician.

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Baseline

Day 14 (Week 2)

FMISO PET & MRI (Combined Groups)

Group 1 (Bevacizumab monotherapy) enrolled 2 patients. Group 2 (Bevacizumab+Lomustine) enrolled 9 patients. Any analysis per arm would be meaningless so the outcome data for both groups were lumped together. There was no pre-specified analysis plan to analyze the cohorts separately. Due to production challenges with FMISO, only 4 patients underwent all 3 FMISO-PET scans: baseline, day 14, and day 28. All 4 patients were in Group 2. The remaining 7 patients had MRI scans alone at those visits.

Change in Tumor Blood Flow/Perfusion

Change in Tumor Hypoxic Volume

Blood Vessel Permeability (Ktrans Change on MRI Scan)

Tumor Blood Flow Measured by MRI Perfusion

Overall Study

Nervous System Diseases

Brain Neoplasms

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Immunoglobulins, Intravenous

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Bevacizumab 10 mg/kg by vein (IV) over 90 minutes on Days 1, 15, and 29 of 6 week cycle.

Bevacizumab 5 mg/kg IV over 90 minutes on Day 1 and 22 (every 3 weeks) of 6 week cycle. Lomustine starting dose of 75 mg/m2 administered orally at sleep time on Day 3 of every 6 week cycle.

10 mg/kg by vein (IV) over 90 minutes on Days 1, 15, and 29 of 6 week cycle.

Standard Dose Bevacizumab

5 mg/kg IV over 90 minutes on Day 1 and 22 (every 3 weeks) of 6 week cycle.

Low Dose Bevacizumab

Starting dose of 75 mg/m2 administered orally at sleep time on Day 3 of every 6 week cycle.

John DeGroot, MD

The goal of this clinical research study is to learn if the combination of bevacizumab and lomustine can help to control glioblastoma. The safety of this combination will also be studied.

The Study Drugs:

Bevacizumab is designed to prevent or slow down the growth of cancer cells by blocking the growth of blood vessels.

Lomustine is designed to damage the DNA (genetic material of cells) of tumor cells, which may cause the tumor cells to die.

Study Groups:

If you are found to be eligible to take part in this study, you will be randomly assigned (as in the flip of a coin) to 1 of 2 groups. You will have an equal chance of being in either group.

* If you are in Group 1, you will receive a higher dose of bevacizumab.
* If you are in Group 2, you will receive lomustine and a lower dose of bevacizumab

Study Drug Administration:

Each treatment cycle is 42 days.

If you are in Group 1:

On Days 1, 15, and 29 of every cycle, you will receive bevacizumab by vein over 90 minutes.

If you are in Group 2:

* On Days 1 and 22 of every cycle, you will receive bevacizumab by vein over 90 minutes.
* On Day 3 of every cycle, you will take lomustine by mouth 1 time a day. You should take lomustine at bedtime 1 hour before or 2 hours after your last meal of the day with 1 cup (about 8 ounces) of water.

Study Visits:

If you are in Group 1 or 2, every 6 weeks:

* You will be asked about any drugs you may be taking and if you have had any side effects.
* You will have a physical exam, including measurement of your vital signs and weight.
* You will have a neurological exam.
* Your performance status will be recorded.
* You will have an MRI scan.
* If you are on anti-seizure drugs, blood (about 1 teaspoon) will be drawn to measure the amount of anti-seizure drugs in your blood.

If you are in Group 1:

* During Weeks 1-6, blood (about 3 teaspoons) drawn for routine tests 1 time a week.
* After Week 6, blood (about 3 teaspoons) will be drawn for routine tests every 2 weeks.
* On Weeks 2, 4, and 6, and then every 6 weeks after that, urine will be collected to check your kidney function.

If you are in Group 2:

* During Weeks 1-6, blood (about 3 teaspoons) drawn for routine tests 1 time a week.
* After Week 6, blood (about 3 teaspoons) will be drawn for routine tests every 3 weeks.
* On Weeks 3 and 6, and then every 6 weeks after that, urine will be collected to check your kidney function.

Length of Study:

You may stay on study treatment of lomustine and/or bevacizumab for up to 1 1/2 years. After that, you may continue taking bevacizumab for as long as the study doctor thinks it is in your best interest. You will be taken off study early if the disease gets worse or you experience intolerable side effects.

End of Study Treatment Visit:

After you are off study treatment, you will have an end of study treatment visit. At this visit, you may have some or all of the following tests and procedures performed:

* You will be asked about any drugs you may be taking and if you have had any side effects.
* You will have physical exam, including measurement of your vital signs and weight.
* Blood (about 3 teaspoons) will be drawn for routine tests.
* You will have a neurological exam.
* Your performance status will be recorded.

Long-Term Follow-up:

After the end of study treatment visit, the study staff will call you every 3 months to check how you are doing. Each phone call will take about 5 minutes.

This is an investigational study. Bevacizumab and lomustine are FDA approved drugs and commercially available for the treatment of brain tumors. The use of these drugs in this combination is investigational.

Up to 102 participants will take part in this study. All will be enrolled at MD Anderson.

Standard Dose Bevacizumab Versus Low Dose Bevacizumab Plus Lomustine (CCNU) for Recurrent Glioblastoma Multiforme (GBM)

Randomized Phase II Trial of Standard Dose Bevacizumab Versus Low Dose Bevacizumab Plus Lomustine (CCNU) In Adults With Recurrent Glioblastoma Multiforme

Participants with no disease progression as measured by magnetic resonance imaging (MRI) scans. Participants followed by MRI scans, as used for baseline tumor measurements, and removed from study if progression is documented after any cycle of treatment. PFS determined from date of registration in the trial and not date of randomization into chemotherapy arms (i.e. after surgery for resection of recurrent tumor).

Definition of Modified Radiographic Response Assessment Criteria for Glioblastoma (GBM) . Complete, Partial, Progressive Disease and Stable Disease. Radiographic response determined in comparison to the tumor measurements obtained at baseline (post-radiation scan will be baseline for newly diagnosed GBM and pre-treatment scans will be the baseline for recurrent GBM) for determination of response, and the smallest tumor measurement at either pre-treatment baseline or following initiation of therapy for determining progression.

Overall Survival(OS) is defined: Time of presentation to date of death or censored at last follow-up date

TTP is defined as the time from randomization to time of progressive disease

Adverse Events grade 3 and 4 hematologic toxicities reported in safety profile of bevacizumab (Avastin) in combination with Lomustine in patients with recurrent glioblastoma using Common Terminology Criteria for Adverse Events (CTCAE) version 3.

M.D. Anderson Cancer Center

Bevacizumab 5 mg/kg IV over 90 minutes on Day 1 and 22 (every 3 weeks) of 6 week cycle. Lomustine starting dose of 90 mg/m2 administered orally at sleep time on Day 3 of every 6 week cycle. Due to hematologic toxicities, the starting dose was reduced to 75 mg/m2.

Low Dose Bevacizumab + Lomustine

<=50 years

>50 years

Age, Customized

United States

Region of Enrollment

KPS index scores range from 0 to 100. A higher score means the patient is better able to carry out daily activities.

Karnofsky Performance Status (KPS)

Recurrence of cancer prior to treatment on study.

# Previous recurrence

Dr. John F de Groot/Chair Ad Interim, Neuro-Oncology

Progression Free Survival (PFS)

Complete Response

Partial Response

Progressive Disease

Stable Disease

Radiographic Response (RR)

6-month Progression-free Survival (PFS-6)

Overall Survival (OS)

Data were not collected for the outcome for Time to Progression (TTP)

Time to Progression (TTP)

Summary of Treatment Related Toxicities

Anti-Inflammatory Agents

Antirheumatic Agents

Analgesics

Capecitabine

Temozolomide

Thioguanine

Celecoxib

Carmustine

Antimetabolites

Anti-Inflammatory Agents, Non-Steroidal

Analgesics, Non-Narcotic

Cyclooxygenase 2 Inhibitors

Cyclooxygenase Inhibitors

Enzyme Inhibitors

Anaplastic Tumors - 6-TG 80 mg/m\^2 orally (PO) every 6 hours Day 1-3; Temozolomide 150 mg/m\^2 PO daily Days 4-8, after 6 day rest Capecitabine 825 mg/m\^2 and Celebrex 400 mg PO every 12 hours Day 14-27 for 28 day course.

Anaplastic Tumors - 6-TG 80 mg/m\^2 PO every 6 hours Day 1-3, Lomustine 100 mg/m\^2 PO on Day 4; Capecitabine 825 mg/m\^2 PO every 12 hours Days 11-24, and Celebrex 400 mg PO every 12 hours Days 11-24.

Participants if previously received Temozolomide but not Lomustine (CCNU) will receive Lomustine; or if had Gliadel wafers and Temozolomide with radiotherapy (XRT) will receive Temozolomide.

Glioblastoma Multiforme - 6-TG 80 mg/m\^2 PO every 6 Hours Day 1-3; Capecitabine 825 mg/m\^2 PO every 12 hours Days 14-27 and Celebrex 400 mg PO every 12 hours Day 11-24; Temozolomide 150 mg/m\^2 PO daily Days 4-8 OR CCNU (Lomustine) 100 mg/m2 orally Day 4 of each 42-day cycle.

Participants receive Temozolomide if not had previous treatment and if had prior CCNU. Those previously treated with Temozolomide but not CCNU receive CCNU, and those that had Gliadel and Temozolomide with XRT receive Temozolomide.

Arms 1,3 = 825 mg/m\^2 By Mouth (PO) Every 12 Hours on Day 14-27; Arms 2,3 = 825 mg/m\^2 PO Every 12 Hours on Day 11-24.

Arms 1,3 = 400 mg PO Every 12 Hours On Day 14-27; Arms 2,3 = 400 mg PO Every 12 Hours On Day 11-24.

Celecoxib (Celebrex)

Arms 1,3 = 150 mg/m\^2 PO Daily On Day 4-8.

Arms 1,2,3 = 80 mg/m\^2 PO Every 6 Hours on Day 1-3.

6-Thioguanine

Charles Conrad, MD

The goal of this clinical research study is to learn if the combination of 6-Thioguanine, Xeloda (capecitabine), and Celebrex (celecoxib) with Temodar (temozolomide) or Lomustine (CCNU) is effective in the treatment of recurrent or progressive anaplastic glioma or glioblastoma multiforme in patients who have failed previous treatments. The safety of these combination treatment will also be studied.

Objectives:

1.1 To determine the efficacy, as measured by 12 month progression-free survival, of TEMOZOLOMIDE or CCNU with 6-THIOGUANINE followed by CAPECITABINE and CELECOXIB in the treatment of patients with recurrent and/or progressive anaplastic gliomas or glioblastoma multiforme.

1.2 To determine the long-term toxicity of TEMOZOLOMIDE or CCNU with 6-THIOGUANINE followed by CAPECITABINE and CELECOXIB in recurrent anaplastic glioma or glioblastoma multiforme patients treated in this manner.

1.3 To determine the clinical relevance of genetic subtyping tumors as a predictor of response to this chemotherapy and long term survival

Capecitabine is a drug that damages the DNA (deoxyribonucleic acid) of tumor cells and blocks the function of DNA and RNA (ribonucleic acid) of tumor cells. These actions help to kill the tumor cells.

Celecoxib is a drug that may help to prevent the development of some types of cancer by blocking a type of enzyme (COX-2) that is found in tumor cells.

Temozolomide and CCNU are the current standard treatment for malignant brain tumors. Both drugs work by damaging the DNA (deoxyribonucleic acid) of tumor cells to kill these tumor cells.

6-Thioguanine is a drug that helps to increase the effects of Temozolomide and CCNU on tumor cells.

Depending on the previous treatment you have received, you will be treated according to Arms 1, 2, or 3.

If you have not received temozolomide before, you will be treated on Arm 1. If you have received temozolomide before but only during radiation therapy and not as chemotherapy afterwards and the treatment was over 6 months ago, you will be treated with temozolomide according to Arm 1.

If you have not received lomustine or carmustine, you will be treated on Arm 2. If you have received Gliadel wafers at surgery greater than 6 months ago and have not been treated with lomustine or carmustine, you will be treated with CCNU according to Arm 2.

Arm 3 will include glioblastoma multiforme patients who may be treated with either temozolomide or lomustine according to the above guidelines and regimens described in Arms 1 and 2.

Arm 1:

Treatment will begin with 6-thioguanine taken by mouth 4 times a day (every 6 hours) for 3 days in a row (Days 1-3). This will be followed by temozolomide taken by mouth at bedtime for 5 days in a row (Days 4-8). After a rest period of 6 days, capecitabine and celecoxib will be taken by mouth twice a day (12 hours apart) for 14 days (Days 14-27). Each cycle of treatment on arm 1 will be 28 days.

Arm 2:

Treatment will begin with 6-thioguanine taken by mouth 4 times a day (every 6 hours) for 3 days in a row (Days 1-3). This will be followed by lomustine taken by mouth at bedtime for 1 day (Day 4). After a rest period of 1 week, capecitabine and celecoxib will be taken by mouth twice a day (12 hours apart) for 14 days (Days 11-24). Each cycle of treatment on arm 2 will take 42 days.

Blood tests (less than 2 teaspoons) will be repeated every 2 weeks and before each new cycle of treatment (a total of about 2 tablespoons). The neurological exam, anticonvulsant level blood tests and the stool test for blood, will be repeated before every cycle on Arms 2 and 3 (CCNU) and before every 2 cycles on Arms 1 and 3 (temozolomide). Kidney function will be evaluated from the blood tests before every other course. Patients taking anticoagulants (coumadin, warfarin) will have procedures to test the clotting ability of the blood before each cycle or more frequently if the doctor feels it is necessary.

Arm 3:

Glioblastoma Multiforme patients will be treated on Arm 3 which will include the drug regimen from either Arm 1 or Arm 2.

Treatment on all arms will continue for 1 year as long as the tumor does not grow and any side effects are tolerable. Treatment may continue beyond one year if your doctor feels it is needed. During the study, you may not receive any other investigational drug or have any other treatment for the cancer, including surgery.

This is an investigational study. All drugs used in this study are FDA approved and are commercially available. A total of 140 patients will take part in this study. All patients will be enrolled at M. D. Anderson.

6-TG, Capecitabine and Celecoxib Plus TMZ or CCNU for Anaplastic Glioma Patients

Combination of 6-Thioguanine, Capecitabine, Celecoxib and Temozolomide or CCNU for Recurrent Anaplastic Glioma and Glioblastoma Multiforme

Progression-free Survival (PFS) at 12 months measured as percentage of participants that are alive and progression-free at 12 months (anaplastic tumors). A combination of neurological examination and MRI brain scan used to define overall response or progression.

Progression-free Survival (PFS) at 6 months measured as percentage of participants that are alive and progression-free at 6 months (glioblastoma multiforme). A combination of neurological examination and MRI brain scan used to define overall response or progression.

6-TG 80 mg/m\^2 orally (PO) every 6 hours Day 1-3; Temozolomide 150 mg/m\^2 PO daily Days 4-8 OR Lomustine 100 mg/m\^2 PO on Day 4; Capecitabine 825 mg/m\^2 every 12 hours; and Celebrex 400 mg PO every 12 hours for 13 days for 28 day course.

Anaplastic Tumors

6-TG 80 mg/m\^2 PO every 6 Hours Day 1-3; Capecitabine 825 mg/m\^2 PO every 12 hours Days 14-27 and Celebrex 400 mg PO every 12 hours Day 11-24; Temozolomide 150 mg/m\^2 PO daily Days 4-8 OR CCNU (Lomustine) 100 mg/m2 orally Day 4 of each 42-day cycle.

Participants receive Temozolomide if not had previous treatment and if had prior CCNU. Those previously treated with Temozolomide but not CCNU receive CCNU, and those that had Gliadel and Temozolomide with XRT receive Temozolomide.

Glioblastoma Multiforme

Charles A. Conrad, MD / Professor

6-TG 80 mg/m\^2 orally (PO) every 6 hours Day 1-3; Capecitabine 825 mg/m\^2 and Celebrex 400 mg PO every 12 hours; Arm 1 Temozolomide (TMZ) 150 mg/m\^2 PO daily Days 4-8 OR Arm 2 Lomustine 100 mg/m\^2 PO on Day 4; Arm 2 Participants if previously received Temozolomide but not Lomustine (CCNU) receive Lomustine; or if had Gliadel wafers and Temozolomide with radiotherapy (XRT) receive Temozolomide.

Participants With Recurrent Anaplastic Glioma

Results from TMZ and CCNU treatment arms (Anaplastic Tumor-Glioma Arms 1 \& 2) were combined in the final analysis because there was no statistically significant difference between them.

12 Month-progression-free Survival for Participants With Anaplastic Tumors

Participants With Glioblastoma Multiforme

6 Month Progression-free Survival for Participants With Glioblastoma

Skin and Connective Tissue Diseases

Neoplasm Metastasis

Melanoma

Neuroendocrine Tumors

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Anti-Infective Agents

Thalidomide

Immunosuppressive Agents

Anti-Bacterial Agents

Lomustine starting dose 30 mg/m\^2 by mouth daily on Day 1 and 29. Temozolomide 75 mg/m\^2 by mouth daily on Days 1 to 42. Thalidomide 200 mg/m\^2 by mouth daily.

Starting dose 30 mg/m\^2 by mouth daily on Day 1 and 29.

75 mg/m\^2 by mouth daily on Days 1 to 42.

Nicholas E. Papadopoulos, MD

The goal of this clinical research study is to find the highest safe dose of lomustine (CCNU, CeeNUTM) that can be given with temozolomide (TemodarTM) and thalidomide (ThalomidTM) in the treatment of metastatic melanoma that has spread to the brain. The safety and effectiveness of this combination therapy will also be studied.

Temozolomide works by blocking a tumor cell's ability to grow. Lomustine is also a chemotherapy drug that works by killing tumor cells. Studies have shown that when lomustine and temozolomide are given together, they decrease the amount of a certain protein, allowing the tumor cells to be more easily killed. Thalidomide is a drug that alters the immune system. it may also interfere with the development of tiny blood vessels that help support tumor growth. Therefore, in theory, it may decrease or prevent the growth of cancer cells.

If you are found to be eligible to take part in this study, you will begin treatment. All 3 drugs will be taken by mouth at home. Each treatment cycle will last for 8 weeks. You will take temozolomide once a day for 6 weeks followed by two weeks off. The best time to take temozolomide is around bedtime, since you must not eat for at least 1 hour before and 1 hour after taking it. The number of capsules you will take is based on your height and weight. You must swallow all the temozolomide capsules at the same time with 8 ounces of water (do not chew them).

You will take thalidomide every day for the entire 8-week cycle. Thalidomide should also be taken near bedtime, usually 30 to 45 minutes before the temozolomide dose. If you are under 70 years of age, you will start at a set dose and take the same dose throughout the study. If you are age 70 or over, the dose will start lower and will increase every 2 weeks until you are taking the prearranged set dose that those under the age of 70 are taking. Your doctor will be watching for side effects as the dose increases and may keep you at a lower dose if necessary.

In the first groups of patients (3-6 patients per group, total up to 18 patients) to be enrolled, each new group of participants will be given a higher dose of lomustine than the previous group until the highest safe dose of lomustine is found or until 18 patients have been enrolled. Responses to these doses will be evaluated. Once the best dose is found, all future participants will receive that dose of lomustine.

You will take 2 doses of lomustine every 8 weeks. You will take the first dose of lomustine on Day 1 of the 8-week cycle. You will take the second dose, which will be half as big as the first dose, on Day 29 (the day after the first 4 weeks) of the 8-week cycle. The dose of lomustine is also based on your height and weight. Lomustine should be swallowed and not chewed.

During treatment, every 2-4 weeks, you will have a complete physical exam and blood drawn for testing (1-2 tablespoons). These tests will let the doctor know if the treatment should be changed, briefly interrupted, or stopped. Women who are able to have children must have a negative pregnancy test every week for the first 4 weeks if they have regular menstruation and every 2 weeks if their periods are irregular.

At the end of 8 weeks, you will have x-rays or scans done again to see how the tumors have responded. If they are the same size or have gotten smaller, you may continue the treatment. You may stay on treatment as long as you are not having severe side effects and your tumor is either staying the same size or getting smaller. Treatment will be stopped if the tumors are getting bigger.

If you are withdrawn from the study for any reason you will be contacted by phone every three months to learn how are you doing health wise.

This is an investigational study. None of the 3 drugs used in this study have been approved by the FDA for the treatment of melanoma. Temozolomide has been approved for the treatment of brain cancer. Thalidomide has not yet been approved for the treatment of cancer. Lomustine is approved for the treatment of brain tumors and Hodgkin's disease. All of the drugs are commercially available. Their use together in this study is experimental.

Up to 18 patients will take part in this Phase I portion of the study, and another 30 patients in Phase II if progresses, with up to 48 patients total. All will be enrolled at M. D. Anderson.

Temozolomide, Thalidomide, and Lomustine (TTL) in Melanoma Patients

A Phase I Study of Temozolomide, Thalidomide, and Lomustine (TTL) in Patients With Metastatic Melanoma in the Brain

Celgene Corporation

Oligodendroglioma

Anaplastic Astrocytoma

Anaplastic Oligodendroglioma

Vincristine

Procarbazine

Tubulin Modulators

Antimitotic Agents

Patients undergo 3D-CRT or IMRT on days 1-5 for 5-7 weeks. Patients also receive procarbazine hydrochloride PO on days 8-21, lomustine PO on day 1 and vincristine sulfate IV on days 8 and 29 of courses 3-8. Treatment repeats every 6-7 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Patients undergo RT as in arm I and receive temozolomide PO QD on days 1-5 for 5-7 weeks. Beginning 4 weeks after completion of concurrent chemoradiotherapy, patients receive adjuvant temozolomide PO QD days 1-5. Treatment with adjuvant temozolomide repeats every 4 weeks for 6-12 courses in the absence of disease progression and unacceptable toxicity.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
FMISO PET Study of Glioblastoma	NCT02076152	Recurrent Gliob...	FMISO PET MRI Bevacizumab CCNU	18 Years -	Massachusetts General Hospital
Standard Dose Bevacizumab Versus Low Dose Bevacizumab Plus Lomustine (CCNU) for Recurrent Glioblastoma Multiforme (GBM)	NCT01067469	Brain Cancer Glioblastoma	Standard Dose B... Low Dose Bevaci... Lomustine	18 Years -	M.D. Anderson Cancer Center
6-TG, Capecitabine and Celecoxib Plus TMZ or CCNU for Anaplastic Glioma Patients	NCT00504660	Anaplastic Glio... Glioblastoma Mu... Brain Cancer	Capecitabine Celecoxib (Cele... Temozolomide Lomustine 6-Thioguanine	12 Years -	M.D. Anderson Cancer Center
Temozolomide, Thalidomide, and Lomustine (TTL) in Melanoma Patients	NCT00527657	Brain Neoplasms Melanoma	Lomustine Temozolomide Thalidomide	18 Years -	M.D. Anderson Cancer Center
Standard Dose Bevacizumab Versus Low Dose Bevacizumab Plus Lomustine (CCNU) for Recurrent Glioblastoma Multiforme (GBM)	NCT01067469	Brain Cancer Glioblastoma	Standard Dose B... Low Dose Bevaci... Lomustine	18 Years -	M.D. Anderson Cancer Center
Standard Dose Bevacizumab Versus Low Dose Bevacizumab Plus Lomustine (CCNU) for Recurrent Glioblastoma Multiforme (GBM)	NCT01067469	Brain Cancer Glioblastoma	Standard Dose B... Low Dose Bevaci... Lomustine	18 Years -	M.D. Anderson Cancer Center
Radiation Therapy With Concomitant and Adjuvant Temozolomide Versus Radiation Therapy With Adjuvant PCV Chemotherapy in Patients With Anaplastic Glioma or Low Grade Glioma	NCT00887146	Brain and Centr...	concomitant tem... radiotherapy procarbazine adjuvant temozo... CCNU vincristine	18 Years -	Alliance for Clinical Trials in Oncology

Spots Global Cancer Trial Database for ccnu

Every month we try and update this database with for ccnu cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for ccnu

Every month we try and update this database with for ccnu cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for ccnu cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.