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Trial record 1 of 1 for:    NCT02844439
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Study of Tesevatinib Monotherapy in Patients With Recurrent Glioblastoma

This study is currently recruiting participants.
See Contacts and Locations
Verified April 2017 by Kadmon Corporation, LLC
Sponsor:
Information provided by (Responsible Party):
Kadmon Corporation, LLC
ClinicalTrials.gov Identifier:
NCT02844439
First received: June 24, 2016
Last updated: April 19, 2017
Last verified: April 2017
  Purpose
This is a multicenter, Phase 2 study to assess the activity of tesevatinib in patients with recurrent glioblastoma.

Condition Intervention Phase
Glioblastoma Recurrent Glioblastoma Brain Tumor Drug: Tesevatinib Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: A Phase 2, Multicenter Study of Tesevatinib Monotherapy in Patients With Recurrent Glioblastoma

Resource links provided by NLM:


Further study details as provided by Kadmon Corporation, LLC:

Primary Outcome Measures:
  • Median Progression-Free Survival (PFS) [ Time Frame: 6 months ]
    The primary objective is to determine the median progression-free survival (PFS-6) by assessing the median number of days from Cycle 1, Day 1 through 6 months of treatment or until disease progression or death.


Secondary Outcome Measures:
  • Progression-Free Survival (PFS) at 6 months- EGFRvIIIpos [ Time Frame: 6 months ]
    To determine the progression-free survival at 6 months (PFS-6) by assessing the percentage of patients with EGFRvIIIpos glioblastoma who are without disease progression or death at 6 months.

  • Progression-Free Survival (PFS) at 6 months - EGFR gene amplified [ Time Frame: 6 months ]
    To determine the median progression-free survival at 6 months (PFS-6) by assessing the percentage of patients with EGFR gene amplified who are without disease progression or death at 6 months.

  • Overall Survival at 9 months [ Time Frame: 9 months ]
    To determine the overall survival (OS) by measuring the percentage of patients alive at 9 months.

  • Overall Survival at 9 months - EGFRvIIIpos [ Time Frame: 9 months ]
    To determine the median overall survival (OS) in the subgroup of patients with EGFRvIIIpos by measuring the percentage of patients alive at 9 months.

  • Median Overall Survival at 9 months - EGFR gene amplified [ Time Frame: 9 months ]
    To determine the overall survival (OS) in the subgroup of patients with EGFR gene amplified tumors by measuring the percentage of patients with EGFR gene amplified tumors alive at 9 months.

  • Evaluate the concentration of tesevatinib in patients with and without systemic steroid treatment. [ Time Frame: 12 months ]
  • Quality of Life in Patient Receiving tesevatinib [ Time Frame: 12 months ]
    To evaluate changes in the neurocognitive function in patients receiving tesevatinib using the M.D. Anderson Symptom Inventory - Brain Tumor questionnaire (MDASI-BT) questionnaires.

  • Quality of Life in Patient Receiving tesevatinib in sub-group [ Time Frame: 12 months ]
    To evaluate changes in the neurocognitive function in the sub-group of patients with EGFRvIIIneg and EGFR gene amplificationneg tumors as compared to those in patients with EGFRvIIIpos and EGFR gene amplificationpos tumors using the M.D. Anderson Symptom Inventory - Brain Tumor questionnaire (MDASI-BT) questionnaires.


Estimated Enrollment: 40
Study Start Date: June 2016
Estimated Study Completion Date: December 2018
Estimated Primary Completion Date: January 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Glioblastoma
The single arm design assessing PFS-6 in the overall population with the ability to detect a rate of 25% is appropriate as a preliminary test of activity in patients with glioblastoma, based on PFS-6 rates seen in randomized studies with bevacizumab [Weathers 2015; Taal 2014; Galanis 2015]. The sample size of this study is also designed to permit the comparison of results with EGFR amplified and non-amplified tumors, as well as EGFRvIII mutated versus wild-type. The sample size is adequate to characterize the safety profile in patients with glioblastoma.
Drug: Tesevatinib
Other Name: KD019, XL647

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Willingness and ability to provide written informed consent and to comply with the study protocol as judged by the investigator
  2. Age ≥ 18 years old
  3. Kamofsky performance status ≥70%
  4. Stable or decreasing dose of corticosteroids within 5 days prior to study 5. enrollment.
  5. For women who are not postmenopausal (i.e., < 12 months after last menstruation) or surgically sterile (absence of ovaries and/or uterus) and who are sexually active: agreement to use an adequate method of contraception (oral contraceptives, intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal jelly) during the treatment period and for at least 6 months after the last dose of study drug.
  6. For male patients who are sexually active and who are partners of premenopausal women: agreement to use a barrier method of contraception during the treatment period and for at least 6 months after the last dose of study drug.
  7. Histologically confirmed glioblastoma. A local pathology report constitutes adequate documentation of histology for study inclusion. Patients with an initial diagnosis of a lower-grade glioma are eligible if a subsequent biopsy was determined to be glioblastoma.
  8. First recurrence after concurrent or adjuvant chemoradiotherapy. Imaging confirmation of first tumor progression or regrowth as defined by the RANO criteria . A minimum of 12 weeks must have elapsed from the completion of radiotherapy to study entry to minimize the potential for MRI changes related to radiation necrosis that might be misdiagnosed as progression of disease, unless there is a new lesion outside the radiation field or unequivocal evidence of viable tumor on histopathological sampling.
  9. Prior treatment with TMZ for low grade glioma or glioblastoma.
  10. No more than one prior line of systemic treatment for glioblastoma. Concurrent and adjuvant TMZ-based chemotherapy, including the combination of TMZ with an investigational agent, is considered one line of therapy.
  11. Prior therapy with gamma knife or other focal high-dose radiotherapy is allowed, but the patient must have subsequent histologic documentation of recurrence, unless the recurrence is a new lesion outside the irradiated field.
  12. Recovery from the toxic effects of prior therapy, with a minimum time of:

    1. ≥ 28 days elapsed from the administration of any prior cytotoxic agents, except ≥ 14 days from vincristine, ≥ 21 days from procarbazine, and ≥ 42 days from nitrosureas
    2. ≥ 28 days elapsed from the administration of any investigational agent
    3. ≥ 14 days elapsed from administration of any non-cytotoxic agent (e.g., interferon, tamoxifen, thalidomide, cis-retinoic acid)
  13. Patients who have undergone recent surgery for recurrent or progressive tumor are eligible provided that:

    1. Surgery must have confirmed the recurrence
    2. There must be residual disease
    3. A minimum of 28 days must have elapsed from the day of surgery to first dose of the study drug. For core or needle biopsy, a minimum of 7 days must have elapsed prior to study entry
  14. Availability of formalin-fixed paraffin-embedded tumor tissue diagnostic of glioblastoma.

Exclusion Criteria:

  1. Concurrent therapeutic intervention (including radiation therapy and NovoTTF).
  2. Prior exposure to EGFR inhibitors.
  3. Prior exposure to bevacizumab or other VEGF- or VEGF-receptor-targeted agent within 8 weeks of study start.
  4. Prior treatment with prolifeprospan 20 with carmustine wafer.
  5. Prior intracerebral agent.
  6. Evidence of recent hemorrhage on baseline MRI of the brain. However, patients with clinically asymptomatic presence of hemosiderin, resolving hemorrhagic changes related to surgery, or presence of punctuate hemorrhage in the tumor are eligible.
  7. Need for urgent palliative intervention for primary disease (e.g., rapidly increasing intracranial pressure, impending herniation, uncontrolled seizures).
  8. Hematology:

    ANC < 1.5 x109/L; Plt < 100 x109/L Hgb < 9.0 g/dL within 7 days prior to enrollment. The use of transfusion or other intervention to achieve Hb ≥ 9 g/dL is acceptable.

  9. T.Bili. ≥ 1.5 x ULN (except in patients diagnosed with Gilbert's disease).
  10. AST(SGOT), ALT(SGPT), or alkaline phosphatase (ALP) ≥ 2.5 x ULN.
  11. S. Creat. > 1.5 x ULN.
  12. K+ or Mg+ < LLN.
  13. In the absence of therapeutic intent to anticoagulate the patient: INR > 1.5 or PT > 1.5 xULN or aPTT > 1.5 xULN Therapeutic anticoagulation.
  14. Known contraindication to MRI, such as cardiac pacemaker, shrapnel or ocular foreign body.
  15. Used any prescription medication during the prior 2 weeks that the investigator judges is likely to interfere with the study or to pose an additional risk to the patient in participating, specifically inhibitors or inducers of cytochrome P450 (CYP)3A4 (refer to Appendix 5). A stable regimen (≥ 4 weeks) of antidepressants of the selective serotonin re-uptake inhibitor (SSRI) class is allowed (common SSRIs include escitalopram oxalate, citalopram, fluvoxamine, paroxetine, sertraline, and fluoxetine).
  16. Taking any drugs associated with torsades de pointes or known to moderately or severely prolong the QTc(F) interval
  17. History of torsades de pointes, ventricular tachycardia or fibrillation, pathologic sinus bradycardia (< 50 bpm), heart block (excluding first degree block, being PR interval only), or congenital long QT syndrome. Patients with a history of atrial arrhythmias should be discussed with the Medical Monitor.
  18. Uncontrolled diabetes, as evidenced by fasting serum glucose level >200 mg/dL
  19. New York Heart Association (NYHA) Grade II or greater congestive cardiac failure.
  20. Has marked prolongation of QTc(F) interval at screening or baseline (QTc[F] interval > 470 msec) using the Fridericia method of correction for heart rate.
  21. History of myocardial infarction (within 12 months) or unstable angina (within 6 months) prior to study enrolment.
  22. History of stroke or transient ischemic attacks within 6 months prior to study enrolment.
  23. Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to study enrolment.
  24. Evidence of bleeding diathesis or coagulopathy (in the absence of therapeutic anticoagulation).
  25. History of intracranial abscess within 6 months prior to study enrolment.
  26. History of another malignancy in the previous 3 years, with a disease-free interval of < 3 years. Patients with prior history of in situ cancer or basal or squamous cell skin cancer are eligible.
  27. Evidence of any active infection requiring hospitalization or IV antibiotics within 2 weeks prior to study enrolment.
  28. Known hypersensitivity to any excipients of tesevatinib.
  29. Inability to swallow or absorb orally-administered medication.
  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: NCT02844439

Locations
United States, Arizona
Center for Neurosciences Recruiting
Tucson, Arizona, United States, 85718
Contact: Margie Pazzi, BSN, RN, CCRP    520-320-2147    mpazzi@neurotucson.com   
United States, California
City of Hope Recruiting
Duarte, California, United States, 91010
Contact: Julie Kilpatrick    626-256-4673 ext 61457      
Contact: Jeriel Lagac    626-256-4673 ext 80216      
University of California, San Francisco (UCSF) Recruiting
San Francisco, California, United States, 94143
Contact: Jessica Carlson    415-514-5521    Jessica.Carlson@ucsf.edu   
United States, Colorado
University of Colorado Cancer Center Recruiting
Aurora, Colorado, United States, 80045
Contact: Lindsey Newnes    720-848-8785    Lindsey.newnes@ucdenver.edu   
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Isabel Arrillaga-Romany, MD, PhD       Iarrillaga@mgh.harvard.edu   
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Caroline Kane, NP    617-632-5749    cckane@partners.org   
United States, Michigan
Henry Ford Hospital Recruiting
Detroit, Michigan, United States, 48202
Contact: John Gaggin       JGAGGIN1@hfhs.org   
Contact: Stephanie Marl       SMARL1@hfhs.org   
United States, New York
Columbia University, Herbert Irving Comprehensive Cancer Center Recruiting
New York, New York, United States, 10032
Contact: Natalie Busby    212-305-8487    nb2718@cumc.columbia.edu   
United States, Ohio
Cleveland Clinic Recruiting
Cleveland, Ohio, United States, 44195
Contact: Sandy Federico, RN    216-636-9410    federis@ccf.org   
Principal Investigator: Manmeet Ahluwalia, MD         
United States, Texas
UT MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Kathy Hunter, RN    713-745-5769    kuhunter@mdanderson.org   
Principal Investigator: John de Groot, MD         
United States, Utah
Huntsman Cancer Institute Recruiting
Salt Lake City, Utah, United States, 84112
Contact: Brett Johnson    801-587-4429    Brett.Johnson@hci.utah.edu   
Contact: Karthik Sonty    801-587-4429    Karthik.Sonty@hci.utah.edu   
Sponsors and Collaborators
Kadmon Corporation, LLC
  More Information

Responsible Party: Kadmon Corporation, LLC
ClinicalTrials.gov Identifier: NCT02844439     History of Changes
Other Study ID Numbers: KD019-208
Study First Received: June 24, 2016
Last Updated: April 19, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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

ClinicalTrials.gov processed this record on July 21, 2017