Overview

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

Status:
Completed
Trial end date:
2020-03-04
Target enrollment:
0
Participant gender:
All
Summary
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).
Phase:
Phase 1/Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Daiichi Sankyo, Inc.
Plexxikon
Collaborator:
Plexxikon
Treatments:
Dacarbazine
Temozolomide
Criteria
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.