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

NCT ID: NCT01790503

Last Updated: 2020-06-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 65 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-07-18
• Study Completion Date: 2020-03-04

Brief 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).

Detailed Description

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.

Conditions

Patients With Newly Diagnosed Glioblastoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Phase 1b dose escalation - 600mg/day PLX3397 cohort

600mg/day PLX3397, Radiation Therapy, and Temozolomide

Group Type: EXPERIMENTAL

PLX3397

Intervention Type: DRUG

Radiation Therapy

Intervention Type: RADIATION

Temozolomide

Intervention Type: DRUG

Phase 1b dose escalation - 800mg/day PLX3397

800mg/day PLX3397, Radiation Therapy, and Temozolomide

Group Type: EXPERIMENTAL

PLX3397

Intervention Type: DRUG

Radiation Therapy

Intervention Type: RADIATION

Temozolomide

Intervention Type: DRUG

Phase 1b dose escalation - 1000 mg/day PLX3397 cohort

1000 mg/day PLX3397, Radiation Therapy, and Temozolomide

Group Type: EXPERIMENTAL

PLX3397

Intervention Type: DRUG

Radiation Therapy

Intervention Type: RADIATION

Temozolomide

Intervention Type: DRUG

Phase 2 - Recommended phase 2 dose of PLX3397

Recommended phase 2 dose of PLX3397 (800mg/day), Radiation therapy, and Temozolomide

Group Type: EXPERIMENTAL

PLX3397

Intervention Type: DRUG

Radiation Therapy

Intervention Type: RADIATION

Temozolomide

Intervention Type: DRUG

Interventions

PLX3397

Intervention Type: DRUG

Radiation Therapy

Intervention Type: RADIATION

Temozolomide

Intervention Type: DRUG

Other Intervention Names

Pexidartinib; TMZ; Temodar

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Plexxikon

INDUSTRY

Sponsor Role: collaborator

Daiichi Sankyo

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Global Clinical Leader

Role: STUDY_DIRECTOR

Daiichi Sankyo

Locations

Northwestern Memorial Hospital

Chicago, Illinois, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Henry Ford Hospital

Detroit, Michigan, United States

Columbia University Medical Center

New York, New York, United States

James Cancer Hospital/Ohio State University

Columbia, Ohio, United States

Huntsman Cancer Institute University of Utah

Salt Lake City, Utah, United States

Seattle Cancer Care Alliance

Seattle, Washington, United States

Countries

United States

References

Gilbert MR, Wang M, Aldape KD, Stupp R, Hegi ME, Jaeckle KA, Armstrong TS, Wefel JS, Won M, Blumenthal DT, Mahajan A, Schultz CJ, Erridge S, Baumert B, Hopkins KI, Tzuk-Shina T, Brown PD, Chakravarti A, Curran WJ Jr, Mehta MP. Dose-dense temozolomide for newly diagnosed glioblastoma: a randomized phase III clinical trial. J Clin Oncol. 2013 Nov 10;31(32):4085-91. doi: 10.1200/JCO.2013.49.6968. Epub 2013 Oct 7.

Reference Type: RESULT

PMID: 24101040 (View on PubMed)

Gilbert MR, Dignam JJ, Armstrong TS, Wefel JS, Blumenthal DT, Vogelbaum MA, Colman H, Chakravarti A, Pugh S, Won M, Jeraj R, Brown PD, Jaeckle KA, Schiff D, Stieber VW, Brachman DG, Werner-Wasik M, Tremont-Lukats IW, Sulman EP, Aldape KD, Curran WJ Jr, Mehta MP. A randomized trial of bevacizumab for newly diagnosed glioblastoma. N Engl J Med. 2014 Feb 20;370(8):699-708. doi: 10.1056/NEJMoa1308573.

Reference Type: RESULT

PMID: 24552317 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

PLX108-08

Identifier Type: -

Identifier Source: org_study_id