Study of Tesevatinib Monotherapy in Patients With Recurrent Glioblastoma

NCT02844439 | Completed Phase 2 Results FDA Drug

• 1 other identifier: KD019-208
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 11

Brief Summary

This is a multicenter, Phase 2 study to assess the activity of tesevatinib in patients with recurrent glioblastoma.

Conditions

Glioblastoma; Recurrent Glioblastoma; Brain Tumor

Outcome Measures

Primary Outcomes (1)

• Efficacy: Median Progression-free Survival (PFS) Rate at 6 Months (PFS-6)

  Proportion (%) of subjects who did not have progressive disease after treatment with tesevatinib at 6 months (PFS-6) after baseline

  6 months

Secondary Outcomes (9)

• Efficacy: Median PFS

  Until disease progression, unacceptable toxicity, subject or clinician decision to discontinue, death, or up to 3 years, whichever occurred first

• Efficacy: Median Overall Survival Rate at 9 Months (OS-9)

  9 months

• Efficacy: Median OS

  Until unacceptable toxicity, subject or investigator decision to discontinue, death, or up to 3 years, whichever occurred first

• Efficacy: Best Overall Response

  Until disease progression, unacceptable toxicity, subject or investigator decision to discontinue, death, or up to 3 years, whichever occurred first

• Efficacy: Objective Response Rate (ORR)

  Until disease progression, unacceptable toxicity, subject or investigator decision to discontinue, death, or 3 years, whichever occurred first

Study Arms (1)

Glioblastoma

EXPERIMENTAL

The single arm design assessing progression-free survival at 6 months (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. 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

Interventions

Tesevatinib DRUG

Also known as: KD019, XL647

Glioblastoma

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Willingness and ability to provide written informed consent and to comply with the study protocol as judged by the investigator
• Age ≥ 18 years old
• Kamofsky performance status ≥70%
• Stable or decreasing dose of corticosteroids within 5 days prior to study 5. enrollment.
• 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.
• 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.
• 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.
• Prior treatment with TMZ for low grade glioma or glioblastoma.
• 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.
• 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.
• Recovery from the toxic effects of prior therapy, with a minimum time of:
• ≥ 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
• ≥ 28 days elapsed from the administration of any investigational agent
• ≥ 14 days elapsed from administration of any non-cytotoxic agent (e.g., interferon, tamoxifen, thalidomide, cis-retinoic acid)
• Patients who have undergone recent surgery for recurrent or progressive tumor are eligible provided that:

You may not qualify if:

• Concurrent therapeutic intervention (including radiation therapy and NovoTTF).
• Prior exposure to EGFR inhibitors.
• Prior exposure to bevacizumab or other VEGF- or VEGF-receptor-targeted agent within 8 weeks of study start.
• Prior treatment with prolifeprospan 20 with carmustine wafer.
• Prior intracerebral agent.
• 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.
• Need for urgent palliative intervention for primary disease (e.g., rapidly increasing intracranial pressure, impending herniation, uncontrolled seizures).
• 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.
• T.Bili. ≥ 1.5 x ULN (except in patients diagnosed with Gilbert's disease).
• AST(SGOT), ALT(SGPT), or alkaline phosphatase (ALP) ≥ 2.5 x ULN.
• S. Creat. \> 1.5 x ULN.
• K+ or Mg+ \< LLN.
• 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.
• Known contraindication to MRI, such as cardiac pacemaker, shrapnel or ocular foreign body.

Sponsors & Collaborators

• Kadmon Corporation, LLC: lead

Study Sites (11)

Center for Neurosciences

Tucson, Arizona, 85718, United States

Location

City of Hope

Duarte, California, 91010, United States

Location

University of California, San Francisco (UCSF)

San Francisco, California, 94143, United States

Location

University of Colorado Cancer Center

Aurora, Colorado, 80045, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Columbia University, Herbert Irving Comprehensive Cancer Center

New York, New York, 10032, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

UT MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

MeSH Terms

Conditions

Glioblastoma; Brain Neoplasms

Interventions

XL647

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Results Point of Contact

• Title: Miranda Ross
• Organization: Kadmon Corporation

Miranda.Ross@kadmon.com

724-778-6170

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: June 24, 2016
• First Posted: July 26, 2016
• Study Start: June 1, 2016
• Primary Completion: April 30, 2020
• Study Completion: April 30, 2020
• Last Updated: September 22, 2021
• Results First Posted: September 22, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (11)