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GlioblastomaPhase 1NCT00734526

Phase I Portion of Phase I/II Sorafenib With Radiation and Temozolomide in Newly Diagnosed Glioblastoma or Gliosarcoma

A Phase 1 study testing Temozolomide, Radiation and Sorafenib in people with Glioblastoma and Gliosarcoma, run by M.D. Anderson Cancer Center at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

The goal of this clinical research study is to find the highest tolerable dose of sorafenib that can be given in combination with temozolomide. The safety of this combination will also be studied. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Glioblastoma, Gliosarcoma
What is being tested?
Temozolomide, Radiation and Sorafenib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
18 participants
Where
1 siteUnited States
Study dates
18 Dec 2008to Dec 2012
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histopathologically proven diagnosis of glioblastoma. Since gliosarcoma is a variant of glioblastoma, gliosarcoma is also an eligible diagnosis.
  • Patients must have at least 1 block of tumor tissue available for submission to the central pathologist for analysis of gene expression status by QRT-PCR; there must be at least 1 cm^2 of tumor from the block when cut on a slide: fresh frozen tumor tissue acquisition is also encouraged, but not required. Unstained slide submission without a block submission is not acceptable for study entry.
  • Diagnosis must be established by open biopsy or tumor resection. Patients who have only had a stereotactic biopsy are not eligible..
  • The tumor must have a supratentorial component.
  • Patients must have recovered from the effects of surgery, postoperative infection, and other complications before study registration.
  • All patients must sign an informed consent indicating that they are aware of the investigational nature of this study.
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  • A diagnostic contrast-enhanced MRI or CT scan (if MRI is contraindicated) of the brain must be performed postoperatively in the period between surgery and initiation of radiation therapy.
  • Therapy must begin </=5 weeks after the most recent brain tumor surgery.
  • History/physical examination within 14 days prior to study registration.
  • Neurologic examination within 14 days prior to study registration.
  • Documentation of steroid doses within 14 days prior to study registration and stable or decreasing steroid dose within 5 days prior to registration.
  • Karnofsky performance status of >/= 60.
  • Age >/= 18 years.
  • Patients with well-controlled hypertension are eligible (systolic blood pressure of </= 140 mgHg or diastolic pressure </= 90 mgHg).
  • Complete blood count (CBC)/differential obtained within 14 days prior to study registration, with adequate bone marrow function as defined below: Absolute neutrophil count (ANC) >/= 1500 cells/mm^3; Platelets >/= 100,000 cells/mm^3;Hemoglobin >/= 10 g/dl.
  • Adequate renal function, as defined below: Serum creatinine </= 1.7 mg/dl within 14 days prior to study registration
  • Adequate hepatic function, as defined below: Bilirubin </= 2.0 mg/dl within 14 days prior to study registration; ALT </= 2 x upper limit of normal range (ULN) within 14 days prior to study registration; AST </= 2 x ULN range within 14 days prior to study registration
  • Fasting cholesterol < 300 mg/dL (9.0 mmol/L) and fasting triglycerides < 2.5 times ULN
  • International normalized ratio (INR) < 1.5 or a PT/PTT within normal limits for patients not on anti-coagulation treatment
  • Patients receiving anti-coagulation treatment with an agent such as warfarin or low molecular weight heparin may be allowed to participate with the following criteria: For patients on prophylactic anticoagulation therapy (low-dose warfarin): INR level < 1.5; Patients on prophylactic dose or full dose low molecular weight heparins are eligible provided that the patient has no active bleeding or pathological condition that carries a high risk of bleeding;
  • (20. continued) Patients on full-dose anticoagulants (e.g., warfarin) are eligible provided that both of the following criteria are met: (a) Patient has an in-range INR (usually between 2-3) on a stable dose or oral anticoagulant or on a stable dose of low molecular weight heparin. (b) Patient has no active bleeding or pathological condition that carries a high risk of bleeding.
  • If the patient's mental status precludes his/her giving informed consent, written informed consent may be given by the responsible family member.
  • For females of child-bearing potential, negative serum pregnancy test within 72 hours prior to starting temozolomide
  • Women of childbearing potential and men must agree to use adequate contraception (barrier method of birth control) prior to study entry and for the duration of study participation. Men should use adequate birth control for at least six months after the last administration of sorafenib or temozolomide.

Who cannot join

  • Prior invasive malignancy (except for non-melanomatous skin cancer) unless disease free for >/= 3 years.
  • Recurrent or multifocal malignant gliomas
  • Metastases detected below the tentorium or beyond the cranial vault.
  • Prior chemotherapy or radiosensitizers for cancers of the head and neck region; note that prior chemotherapy for a different cancer is allowable.
  • Prior use of Gliadel wafers or any other intratumoral or intracavitary treatment are not permitted.
  • Prior radiotherapy to the head or neck (except for T1 glottic cancer), resulting in overlap of radiation fields.
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  • Severe, active co-morbidity, defined as follows: Cardiac disease - Congestive heart failure > class II New York Heart Association (NYHA). Patients must not have unstable angina (anginal symptoms at rest) or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months; Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy; Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration; Chronic Hepatitis B or C infection;
  • (7. continued) Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration; Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects;
  • (7. continued) Known history or symptoms and laboratory results consistent with Acquired Immune Deficiency Syndrome (AIDS) based upon current CDC definition (note, however, that HIV testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive); Major medical illnesses or psychiatric impairments that in the investigator's opinion will prevent administration or completion of protocol therapy;
  • (7. continued) Active connective tissue disorders, such as lupus or scleroderma, that in the opinion of the treating physician may put the patient at high risk for radiation toxicity; Arterial thrombotic or embolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months; Pulmonary hemorrhage/bleeding event > Common Toxicity Criteria for Adverse Effects (CTCAE) Grade 2 within 4 weeks of first dose of study drug;
  • (7. continued) Any other hemorrhage/bleeding event > CTCAE Grade 3 within 4 weeks of first dose of study drug; Serious non-healing wound, ulcer, or bone fracture; Evidence or history of bleeding diathesis or coagulopathy
  • Uncontrolled hypertension defined as systolic blood pressure > 140 mmHg or diastolic pressure > 90 mmHg, despite optimal medical management.
  • Major surgery, open biopsy or significant traumatic injury within 4 weeks of first study drug.
  • Use of St. John's Wort or rifampin (rifampicin).
  • Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic.
  • No tissue provided for histopathologic review and QRT-PCR analysis.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: A Phase I Study of Sorafenib With Radiation and Temozolomide in Newly Diagnosed Glioblastoma or Gliosarcoma

The goal of this clinical research study is to find the highest tolerable dose of sorafenib that can be given in combination with temozolomide. The safety of this combination will also be studied.

Read the detailed description

The Study Drugs:

Sorafenib is designed to stop the cell growth and to block the formation of new blood vessels (the tubes that carry blood around the body), which are involved in the growth and development of tumors.

Temozolomide is designed to kill cancer cells by damaging DNA (the genetic material of cells). The damaged DNA may cause tumor cell death.

Study Groups:

If you are found to be eligible to take part in this study, you will be assigned to 1 of 4 groups based on when you joined this study. You will remain in the same group for the entire study. In this study, the dose of the study drugs is different from group to group, and the doses are also different during and after radiation. During radiation, the study drugs and doses are as follows:

  • If you are in Group 1, you will take temozolomide.
  • If you are in Groups 2 or 3, you will take temozolomide and the lower dose of sorafenib.
  • If you are in Group 4, you will take temozolomide and the higher dose of sorafenib.
  • During radiation, all the groups will take the same dose of temozolomide.

After Radiation:

  • If you are in Groups 1 or 2, you will take the higher dose of temozolomide on a shorter cycle and the higher dose of sorafenib.
  • If you are in Group 3, you will take the lower dose of temozolomide on a longer cycle and the lower dose of sorafenib.
  • If you are in Group 4, you will take the lower dose of temozolomide on a longer cycle and the higher dose of sorafenib.

The amount of study drugs you receive may change if you experience side effects. If at any time you experience any intolerable side effects, tell the study doctor right away.

Study Drug Administration:

During Radiation:

As a part of standard of care, you will receive radiation therapy Monday-Friday for a total of 30 radiation treatments (about 6 weeks).

Every day while you are receiving radiation, you will take the temozolomide by mouth once a day (up to a maximum of 7 weeks). On Monday-Friday, you will take temozolomide 1 hour before radiation therapy. On Saturday and Sunday, you will take temozolomide in the morning.

You should swallow temozolomide whole, one right after the other, without chewing them. If you vomit while taking temozolomide, you cannot take more capsules before the next scheduled dose. They should be taken on an empty stomach (at least 1 hour before and 2 hours after eating) with 1 cup (about 8 oz.) of water.

Every day while you are receiving radiation, you will take sorafenib by mouth 2 times a day (in the morning and evening) (up to a maximum of 7 weeks). You should take sorafenib without food (1 hour before or 2 hours after eating), with at least 1 cup (8 oz.) of water. If you are in Group 1, you will not take sorafenib.

After Radiation:

You will not take the study drug(s) for about 4 weeks after the radiation therapy ends.

After 4 weeks:

  • If you are in Group 1 or 2, on Days 1-5 of every 28-day study cycle, you will take temozolomide by mouth once a day.
  • If you are in Group 3 or 4, on Days 1-21 of every cycle, you will take temozolomide by mouth once a day.

Every day of each cycle, all groups will take sorafenib by mouth 2 times (in the morning and evening).

Study Visits:

During Radiation:

Once a week while you are receiving radiation therapy, you will be asked about any drugs you may be taking and if you have experienced any side effects. Your blood pressure will be measured. Blood (about 3-4 teaspoons) will be drawn for routine tests.

After Radiation:

About 3-4 weeks after the end of radiation therapy, you will have a MRI scan to check the status of the disease.

On Day 1 of every cycle, the following tests and procedures will be performed:

  • You will have a physical exam, including measurement of your vital signs.
  • You will have a neurological exam.
  • You will have a performance status evaluation.
  • You will be asked about any drugs you may be taking and if you have experienced any side effects.
  • Blood (about 3-4 teaspoons) will be drawn for routine tests.

On Days 7, 14, and 21 of Cycle 1 and on Days 7 and 14 (or 21) of Cycles 2 and beyond, blood (about 3-4 teaspoons) will be drawn for routine tests.

On Day 1 of every other cycle (Cycles 3, 5, 7, and so on), you will have a MRI scan to check the status of the disease.

Every week of Cycle 1, your blood pressure will be measured.

Length of Study:

You will be on study for about 15 months total. You will be taken off study early if the disease gets worse or you experience intolerable side effects.

End-of-Study Visit:

After you go off study, you will have an end-of-study visit. At this visit, the following tests and procedures will be performed:

  • You will have a physical exam, including measurement of your weight and vital signs.
  • You will be have a performance status evaluation.
  • You will be asked about any drugs you may be taking and if you have experienced any side effects.
  • You will have a neurological exam.
  • You will have a MRI scan to check the status of the disease.
  • Blood (about 3 teaspoons) will be drawn for routine tests.

This is an investigational study. Temozolomide is FDA approved and commercially available for the treatment of brain tumors. Sorafenib is FDA approved and commercially available for the treatment of kidney cancer, but it is experimental for use in brain tumors. In addition, the combination of temozolomide and Sorafenib is experimental for use in brain tumors. At this time, the combination is only being used in research.

Up to 51 participants will take part in this study. All will be enrolled at M. D. Anderson.

Keywords
Glioblastoma, Gliosarcoma, Brain Cancer, Sorafenib, Temozolomide, Radiation, Radiotherapy, XRT
Medical subject headings
Glioblastoma, Gliosarcoma, Brain Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TemozolomideDrug

    Groups 1 \& 2: 75 mg/m^2 Once Daily by Mouth During Radiation; 4 Weeks after Completion of Radiation, 150-200 mg/m^2 Once Daily by Mouth Days 1-5 of 1st 28-Day Cycle, then 75 mg/m^2 Once Daily by Mouth Days 1-5 for Subsequent 28-Day Cycles.

    Groups 3 \& 4: 75 mg/m^2 Once Daily by Mouth During Radiation; 4 Weeks after Completion of Radiation, 75-100 mg/m^2 Once Daily by Mouth Days 1-21 every 28-Day Cycle.

  • RadiationRadiation

    Also called Radiotherapy, XRT

    Total of 60 Gy delivered over 30 Days (approximately 6 weeks).

  • SorafenibDrug

    Also called BAY43-9006

    Group 1: 4 Weeks after Completion of Radiation, 400 mg Twice Daily by Mouth.

    Group 2: 200 mg Twice Daily by Mouth during Radiation; 4 Weeks after Completion of Radiation, 400 mg Twice Daily by Mouth.

    Group 3: 200 mg Twice Daily by Mouth during Radiation; 4 Weeks after Completion of Radiation, 200 mg Twice Daily by Mouth.

    Group 4: 400 mg Twice Daily by Mouth during Radiation; 4 Weeks after Completion of Radiation, 400 mg Twice Daily by Mouth.

Study groups in NCT00734526
Study groupRoleWhat they receive
Dose Level 1ExperimentalTemozolomide + Radiation, Followed by Higher Dose Temozolomide in a Shorter Cycle Temozolomide 75mg/m^2 daily during radiation therapy, and 150mg/m^2 in the first cycle of adjuvant therapy. Dose Level 1 will receive sorafenib in the adjuvant phase (following radiation therapy) at the dose of 400mg BID in combination with standard dose temozolomide 150-200 mg/m^2 two days out of 28 day cycle. Radiotherapy 2.0 Grey (Gy)/day given daily 5 days per week for total of 60.0 Gy over 6 weeks.
Receives: Drug: Temozolomide; Radiation: Radiation; Drug: Sorafenib
2ExperimentalTemozolomide + Lower Dose Sorafenib + Radiation, Followed by Higher Dose Temozolomide in a Shorter Cycle + Higher Dose Sorafenib
Receives: Drug: Temozolomide; Radiation: Radiation; Drug: Sorafenib
3ExperimentalTemozolomide + Lower Dose Sorafenib + Radiation, Followed by Lower Dose Temozolomide in a Longer Cycle + Lower Dose Sorafenib
Receives: Drug: Temozolomide; Radiation: Radiation; Drug: Sorafenib
4ExperimentalTemozolomide + Higher Dose Sorafenib + Radiation, Followed by Lower Dose Temozolomide in a Longer Cycle + Higher Dose Sorafenib
Receives: Drug: Temozolomide; Radiation: Radiation; Drug: Sorafenib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Phase I: Sorafenib Maximum Tolerated Dose (MTD)

    MTD of sorafenib given during (concurrently with) external beam radiation therapy and daily temozolomide (75mg/m^2), and with standard dose temozolomide (150-200mg/m^2 5 days out of 28) after radiation therapy (adjuvant) in patients with newly diagnosed glioblastoma or gliosarcoma

    MTD is defined as the dose level below which there were 2 or more participants out of 6 with Dose-limiting toxicities (DLTs). by the conclusion of the first cycle of post-radiation therapy (14 weeks),

    Measured: 4 Week Cycles

  2. Second MTD

    maximum tolerated dose (MTD) of sorafenib given during (concurrently with) external beam radiation therapy and daily temozolomide (75mg/m2), and with dose dense temozolomide (100mg/m2 21 days out of 28) after radiation therapy (adjuvant) in patients with newly diagnosed glioblastoma or gliosarcoma

    Measured: 4 weeks

Secondary outcomes (1)

  1. Phase II: Time to Progression

    Measured: 15 Months or till progressive disease, severe toxicity or death.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Aug 2008 (estimated)
  2. Study start18 Dec 2008
  3. Primary completionDec 2012
  4. Study completionDec 2012

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
18 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00734526
Sponsor's protocol ID
2008-0059
Other IDs
NCI-2012-01617
Status last verified
Nov 2018
First submitted
12 Aug 2008
Last updated
9 Nov 2018
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Temozolomide, Radiation and Sorafenib in people with Glioblastoma and Gliosarcoma, run by M.D. Anderson Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 24 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 9 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early. Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase I: Sorafenib Maximum Tolerated Dose (MTD) (time frame: 4 Week Cycles). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00734526.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Nov 2018.

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