A Phase 2 Study of PLX3397 in Patients With Recurrent Glioblastoma

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Plexxikon
ClinicalTrials.gov Identifier:
NCT01349036
First received: May 4, 2011
Last updated: April 3, 2013
Last verified: April 2013
  Purpose

The objective of this study is to evaluate the response of subjects with recurrent glioblastoma to continuous therapy of PLX3397.


Condition Intervention Phase
Recurrent Glioblastoma
Drug: PLX3397
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2 Study of Orally Administered PLX3397 in Patients With Recurrent Glioblastoma

Resource links provided by NLM:


Further study details as provided by Plexxikon:

Primary Outcome Measures:
  • Safety-Subject incidence of adverse events [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    Subjects will take oral doses of PLX3397 twice a day. Physical examinations, vital signs, 12-lead electrocardiograms (ECG), adverse events, hematology and serum chemistry will be used to assess safety throughout the study. Adverse events will be monitored and reviewed for safety issues/abnormal changes in the above mentioned tests.

  • Efficacy-6 month progression free survival rate (PFS6), median duration of response, overall survival (OS) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    After discontinuation of PLX3397 for reasons other than progression of disease, patients will be followed every 3 months, or as clinically indicated, until progression of disease or death is documented.

  • Efficacy-Overall response rate (ORR) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Subjects will have an MRI brain scan within 28 days of starting dosing with PLX3397 and then every 8 weeks thereafter. Response to treatment will be evaluated using the Response Assessment in Neuro-Oncology (RANO) criteria.


Estimated Enrollment: 40
Study Start Date: August 2011
Estimated Study Completion Date: September 2013
Estimated Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: PLX3397-Cohort 1
10 patients with recurrent glioblastoma who require reoperation will be treated with PLX3397 for 7 days prior to surgery and their tumor tissue will be evaluated for pharmacokinetic levels and pharmacodynamic effects.
Drug: PLX3397
Capsules administered once or twice daily, continuous dosing
Experimental: PLX3397-Cohort 2
30 patients will be orally dosed with PLX3397 continuously on 28 day cycles.
Drug: PLX3397
Capsules administered once or twice daily, continuous dosing

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female patients ≥18 years old with a life expectancy of at least 8 weeks
  • Radiographically proven recurrent (≥ first relapse), intracranial GBM
  • For all patients, availability of at least 10 unstained slides (or archival tumor block sufficient to generate at least 10 unstained slides) from any previous GBM surgery
  • Previous treatment with external beam radiation and temozolomide chemotherapy
  • Before the first dose of PLX3397,adequate recovery from toxicity of prior therapy as follows:

>28 days for cytotoxic therapy >42 days for nitrosoureas >28 days for bevacizumab >7 days for non cytotoxic therapy such as interferon, tamoxifen, thalidomide, cis-retinoic acid, or erlotinib

  • Women of child-bearing potential must have a negative pregnancy test within 7 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.
  • Karnofsky performance status of ≥60
  • Adequate hematologic, hepatic, and renal function (absolute neutrophil count ≥1.0 x 109/L, Hgb >9 g/dL, platelet count ≥50 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:

  • Investigational drug use within 28 days of the first dose of PLX3397
  • GBM progression within 3 months of previous radiation by RANO criteria
  • History of Grade 2 (CTCAE v4) or greater acute intracranial hemorrhage
  • Previous failure of bevacizumab or other VEGF therapy except in a first line setting
  • History of malignant glioma with co-deletion of 1p/19q
  • A concurrent active cancer that requires non-surgical therapy (e.g. chemotherapy, radiation, adjuvant therapy). Prior history of other cancer is allowed, as long as there was no active disease within the prior 3 years.
  • Refractory nausea and vomiting, malabsorption, biliary shunt, or significant bowel resection that would preclude adequate absorption
  • 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
  • QTc ≥450 msec at Screening
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01349036

Locations
United States, California
University California, Los Angeles
Los Angeles, California, United States, 90095
University California, San Francisco
San Francisco, California, United States, 94143
United States, Massachusetts
Dana Faber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
United States, Texas
University of Texas, MD Anderson Cancer Center
Houston, Texas, United States, 77030
United States, Utah
Huntsman Cancer Institute University of Utah
Salt Lake City, Utah, United States, 84132
Sponsors and Collaborators
Plexxikon
  More Information

No publications provided

Responsible Party: Plexxikon
ClinicalTrials.gov Identifier: NCT01349036     History of Changes
Other Study ID Numbers: PLX108-04
Study First Received: May 4, 2011
Last Updated: April 3, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Plexxikon:
GBM
Glioblastoma
brain cancer

Additional relevant MeSH terms:
Glioblastoma
Astrocytoma
Glioma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Neuroectodermal Tumors

ClinicalTrials.gov processed this record on October 29, 2014