A Phase 1b/2 Study of PLX3397 + Radiation Therapy + Temozolomide in Patients With Newly Diagnosed Glioblastoma



Status:Active, not recruiting
Conditions:Brain Cancer
Therapuetic Areas:Oncology
Healthy:No
Age Range:18 - Any
Updated:12/29/2018
Start Date:August 2013
End Date:October 2019

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An Open Label Phase 1b/2 Study of Orally Administered PLX3397 in Combination With Radiation Therapy and Temozolomide in Patients With Newly Diagnosed Glioblastoma

The study objectives are to assess the potential for PLX3397 to improve the efficacy of
standard of care radiation therapy (RT) + temozolomide in patients with newly diagnosed
glioblastoma (GBM).

Study drug will be administered twice daily for 7 days prior to the initiation of RT
(radiation therapy)and will continue twice daily during the course of RT. The RT schedule
will be once daily for 5 days per week for 6 weeks (total radiation dose of 60 Gy. Oral
temozolomide will be administered once daily (7 days per week) for the duration of RT. Four
weeks after the completion of the course of RT, patients will be started on once-daily
adjuvant temozolomide (Day 1-5 of a 28 day cycle) and PLX3397 twice daily (28 days of a 28
day cycle) for up to 12 cycles in the absence of progressive disease or unacceptable
toxicities. After discontinuation of study drug, patients will continue to be followed for OS
every 6 months. For patients participating in the run-in Phase 1b of the study, intra patient
dose escalation will be permitted after a RP2D has been established. The Phase 2 portion of
the study will enroll patients to be treated with PLX3397 at RP2D.

For the Phase 1b portion of the study, 2 cohorts (800 mg/day and 1000 mg/day) are planned to
be enrolled at approximately 7-10 sites. Each cohort will consist of approximately 7
patients. Therefore, a minimum of 14 patients are planned to be enrolled in Phase 1b.
Additional patients may be required for replacement patients, or if lower dose cohorts (600
mg or 400 mg) are required. For the Phase 2 portion of the study, enrollment is planned to
include approximately 44 patients.

Inclusion Criteria:

- Male or female patients ≥18 years old.

- Histologically confirmed definitive GBM or gliosarcoma by partial or complete surgical
resection (i.e. not by biopsy only) within 5 weeks prior to PLX3397 administration
(C1D1). Tumor must have a supratentorial component. For all patients, availability of
a surgical paraffin tumor block sufficient to generate at least 20 unstained slides;
or, if a paraffin tumor block is unavailable, at least 20 unstained slides.

- The patient must have recovered from the effects of surgery, post-operative infection,
and other complications before study registration.

- A diagnostic contrast-enhanced MRI or CT scan of the brain must be performed
preoperatively and postoperatively prior to the initiation of radiotherapy, within 28
days (preferably 14 days) prior to C1D1.

- Patients unable to undergo MR imaging because of non-compatible devices can be
enrolled, provided pre- and post-operative contrast-enhanced CT scans are obtained and
are of sufficient quality.

- Patients must receive RT at the participating institution.

- Women of child-bearing potential must have a negative pregnancy test within 14 days of
initiation of dosing and must agree to use an acceptable method of birth control while
on study drug and for 3 months after the last dose. Women of non-childbearing
potential may be included if they are either surgically sterile or have been
postmenopausal for ≥1 year. Men of child-bearing potential must also agree to use an
acceptable method of birth control while on study drug, and for 3 months after the
last dose.

- Karnofsky performance status of ≥70.

- Adequate hematologic, hepatic, and renal function (absolute neutrophil count ≥1.5x
109/L, Hgb >10 g/dL, platelet count ≥100 x 109/L, AST/ALT ≤2.5x ULN, creatinine ≤1.5x
ULN).

- Willing and able to provide written informed consent prior to any study related
procedures and to comply with all study requirements.

Exclusion Criteria:

- Evidence of recurrent GBM or metastases detected outside of the cranial vault.

- Investigational drug use within 28 days of the first dose of PLX3397 or concurrently.

- Prior use of Gliadel wafers or any other intratumoral or intracavitary treatment.

- Prior radiation or chemotherapy for glioblastoma or glioma.

- Prior chemotherapy or radiosensitizers for cancer of the head and neck (except for T1
glottic cancer) that would result in an overlap of radiation fields.

- Prior allergic reaction to temozolomide.

- History of Grade 2 (CTCAE v4) or greater acute intracranial hemorrhage.

- Active cancer (either concurrent or within the last 3 years) that requires
non-surgical therapy (e.g. chemotherapy or radiation therapy), with the exception of
surgically treated basal or squamous cell carcinoma of the skin, melanoma in-situ, or
carcinoma in-situ of the cervix.

- Chronic active hepatitis B or C.

- Refractory nausea and vomiting, malabsorption, biliary shunt, or significant bowel
resection that would preclude adequate absorption of study drug.

- Patients with serious illnesses, uncontrolled infection, medical conditions, or other
medical history including abnormal laboratory results, which in the investigator's
opinion would be likely to interfere with a patient's participation in the study, or
with the interpretation of the results.

- Women of child-bearing potential who are pregnant or breast feeding.

- At Screening QTcF ≥450 msec for males and ≥470 msec for females.
We found this trial at
9
sites
2000 Circle of Hope Dr
Salt Lake City, Utah 84112
(801) 585-0303
Huntsman Cancer Institute at University of Utah Huntsman Cancer Institute (HCI) is part of the...
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Salt Lake City, UT
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330 Brookline Ave
Boston, Massachusetts 02215
617-667-7000
Beth Israel Deaconess Medical Center Beth Israel Deaconess Medical Center (BIDMC) is one of the...
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Boston, MA
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185 Cambridge Street
Boston, Massachusetts 02114
617-724-5200
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Boston, MA
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825 Eastlake Ave E
Seattle, Washington 98109
(206) 288-7222
Seattle Cancer Care Alliance Seattle Cancer Care Alliance (SCCA) is a cancer treatment center that...
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Seattle, WA
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450 Brookline Ave
Boston, Massachusetts 2215
617-632-3000
Dana-Farber Cancer Institute Since it’s founding in 1947, Dana-Farber has been committed to providing adults...
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Boston, MA
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251 E Huron St
Chicago, Illinois 60611
(312) 926-2000
Northwestern Memorial Hospital Northwestern Memorial is an academic medical center hospital where the patient comes...
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Chicago, IL
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Columbia, OH
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2799 W Grand Blvd
Detroit, Michigan 48202
(313) 916-2600
Henry Ford Hospital Founded in 1915 by auto pioneer Henry Ford and now one of...
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Detroit, MI
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630 W 168th St
New York, New York
212-305-2862
Columbia University Medical Center Situated on a 20-acre campus in Northern Manhattan and accounting for...
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New York, NY
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