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A Phase 2 Open-Label Study of the Efficacy of TPI 287 in Patients With Glioblastoma Multiforme That Has Recurred or Progressed Following Prior Therapy With Radiation Plus Temozolomide


Phase 2
18 Years
N/A
Not Enrolling
Both
Brain Cancer

Thank you

Trial Information

A Phase 2 Open-Label Study of the Efficacy of TPI 287 in Patients With Glioblastoma Multiforme That Has Recurred or Progressed Following Prior Therapy With Radiation Plus Temozolomide


The Study Drugs:

TPI 287 is designed to block a protein that causes cancer cells to resist the effects of
chemotherapy. By blocking the protein, the drug may be able to cause the cancer cells to
shrink or stop growing.

Bevacizumab will be given to patients that are found to have brain damage, as described
below. It is designed to block the growth of new blood vessels. It may help to lower the
amount of brain damage related to tumor tissue death and help limit the symptoms of this
condition.

Study Drug Administration:

On Day 1 of each 21-day study "cycle," you will receive TPI 287 by vein over about 1 hour.

If you experience intolerable side effects, the dose of TPI 287 may be lowered. Your
doctor will tell you more about lowering a dose due to side effects.

To help prevent an allergic reaction to TPI 287, you will also receive the following drugs:

- Benadryl® (diphenhydramine) by vein over 30 minutes, 30-60 minutes before you receive
TPI 287

- Cimetidine by vein over 30 minutes, 30-60 minutes before you receive TPI 287

- Either dexamethasone or methylprednisolone (taken by mouth 12 and 6 hours before you
receive TPI 287; or by vein over 30 minutes at about 30-60 minutes before you receive
TPI 287)

If you have an MRI scan that shows evidence of brain damage related to the tumor tissue
death after you have received TPI 287 for two infusions, you will be eligible to receive
bevacizumab. On Day 1 of Cycle 3 and beyond, if you are eligible, you will receive
bevacizumab by vein over about 60-90 minutes.

Study Visits:

At each study visit, you will be asked about any drugs you may be taking and about any side
effects you may have experienced.

On Day 1 of Cycle 1:

- Your weight and vital signs will be measured.

- If your doctor thinks it is needed, blood (about 1 tablespoon) will be drawn for
routine tests.

On Day 1 of Cycles 2 and beyond:

- You will have a physical exam, including measurement of your weight and vital signs.

- Your performance status will be recorded.

- Blood (about 1 tablespoon) will be drawn for routine tests

On Day 15 of every even-numbered cycle (Cycles 2, 4, 6, and so on), you will have an MRI
scan to check the status of the disease.

Length of Study:

You will be on study for up to 6 months. You may continue to receive the study drug for as
long as you are benefiting. You will be taken off study if the disease gets worse or if you
experience intolerable side effects.

If you are eligible and you receive it, you may continue to receive bevacizumab for as long
as you are benefiting. You will be taken off bevacizumab if the disease gets worse or if
you experience intolerable side effects.

End-of-Treatment Visit:

Within 28 days after you stop receiving the study drug, you will have an end-of-treatment
visit. At this visit, the following tests and procedures will be performed:

- You will be asked about any drugs you may be taking and if you have experienced any
side effects.

- You will have a physical exam, including measurement of your weight and vital signs.

- Your performance status will be recorded.

- Blood (about 1 tablespoon) will be drawn for routine tests.

- You will have an MRI scan to check the status of the disease if you did not have one
within 6 weeks before the end-of-treatment visit.

Long-Term Follow-Up:

Every 3 months for up to 1 year after you stop receiving the study drug, you will be called
and asked about how you are feeling. Each phone call will last about 5-10 minutes.

This is an investigational study. TPI 287 is not FDA approved or commercially available.
It is currently being used for research purposes only. Bevacizumab is FDA approved and
commercially available for the treatment of brain tumors. The use of bevacizumab for brain
damage related to the tumor tissue death is investigational.

Up to 50 patients will take part in this study. All will be enrolled at M. D. Anderson.


Inclusion Criteria:



1. Patients must have histological or cytological documentation of GBM. Patients will be
eligible if the original histology was lower grade glioma and a subsequent diagnosis
of glioblastoma or gliosarcoma is made.

2. Patients must have supratentorial GBM that has radiographic recurrence or progression
following prior radiation therapy and temozolomide for GBM or lower grade glioma, or
the appearance of new lesions on scan, or clinical or neurologic worsening despite
stable disease on the last 2 scans.

3. Patients must have measurable disease on radiologic scan.

4. Patients must be >/= 18 years of age.

5. Patients must have a Karnofsky performance status >/= 60%.

6. Patients must have adequate bone marrow as evidenced by an absolute neutrophil count
>/=1,500/uL and a platelet count >/=100,000/uL.

7. Patients must have adequate renal function as evidenced by serum creatinine <= the
upper limit of normal (ULN)

8. Patients must have adequate hepatic function as evidenced by serum total bilirubin

9. Patients must have recovered from the effects of any prior surgery, radiotherapy or
other chemotherapy with any therapy related adverse events revolved to and at least 12 weeks must have elapsed from the completion of radiotherapy, and 3
weeks from the last dose of Temozolomide.

10. Women of child-bearing potential (includes women who are menopausal for less than 1
year and not surgically sterilized) must have a negative urine or serum pregnancy
test at screening.

11. Sexually active patients must agree to use adequate contraception (two barrier
methods) for the duration of the study.

12. Patients or their legal representative must be able to read, understand and sign an
informed consent form (ICF).

Exclusion Criteria:

1. Patients who have received more than one course of radiation therapy or more than a
total dose of 65 Gy. Patients may have received radiosurgery as part of the initial
therapy (i.e., in addition to one course of radiation therapy); however, the dose
used for the radiosurgery counts against the total dose limit listed above.

2. Patients who have had a second surgery for recurrent disease who have no
radiologically apparent residual disease (contrast-enhanced MRI imaging must have
been performed within 24-48 hours post-operatively).

3. Patient who have received any cytotoxic chemotherapy for treatment of GBM other than
temozolomide (GliadelTM as part of the initial therapy is permitted). However,
patients who have received prior biologic therapy will be eligible.

4. Patients who are receiving concurrent enzyme-inducing anti-epileptic drugs (EIAEDs)
(e.g., carbamazepine, oxcarbazepine, phenytoin, fosphenytoin, phenobarbital and
primidone) or who received EIAEDs within 2 weeks prior to the first dose of study
drug.

5. Patients who are not on a stable or decreasing steroid dose for the previous week
prior to the study enrollment.

6. Patients with an active infection or with a fever >/= 38.5┬░C within 3 days prior to
the study enrollment.

7. Patients who have history of prior malignancy within the past 5 years except for
curatively treated non-melanoma skin cancer or cervical intra-epithelial neoplasia
for which the patient has been disease-free for at least 3 years.

8. Patients with Grade 2 or higher peripheral neuropathy.

9. Patients with New York Heart Association(NYHA) Class 3 or 4 congestive heart failure.

10. Patients with known HIV or Hepatitis B or C.

11. Patients who are pregnant or lactating.

12. Patients with any other medical condition, including mental illness or substance
abuse, deemed by the Investigator to be likely to interfere with the patient's
ability to sign the ICF or his/her ability to cooperate and participate in the study,
or to interfere with the interpretation of the results.

13. Patients who have received prior bevacizumab therapy.

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Progression-Free Survival Rate

Outcome Description:

Patients who are alive without documented evidence of disease progression will be determined to be "progression free" at each study time point. As well, progression-free survival will be calculated from the date of Day 1 Cycle 1 to the date that criteria for progression of disease is first seen.

Outcome Time Frame:

After 9 x 21-day Cycles (6 months)

Safety Issue:

No

Principal Investigator

Charles A. Conrad, MD

Investigator Role:

Study Chair

Investigator Affiliation:

UT MD Anderson Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

2009-0759

NCT ID:

NCT01113463

Start Date:

April 2010

Completion Date:

Related Keywords:

  • Brain Cancer
  • Brain Tumor
  • Central Nervous System
  • CNS
  • Glioblastoma Multiforme
  • GBM
  • TPI 287
  • Radiation Therapy
  • Temozolomide
  • Chemotherapy
  • taxanes
  • Brain Neoplasms
  • Glioblastoma

Name

Location

UT MD Anderson Cancer Center Houston, Texas  77030