TRC105 for Recurrent Glioblastoma

NCT01778530 | Terminated Phase 2 Results

• 2 other identifiers: 13004813-C-0048
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

Background: \- Glioblastoma is an aggressive type of brain cancer that often resists treatment. TRC105 is an experimental drug that blocks the growth of new blood vessels. It is being studied for possible use in treating different kinds of cancer. Researchers want to see if TRC105 can be used to treat glioblastoma that has not responded to standard treatments. Objectives: \- To test the safety and effectiveness of TRC105 in adults who have glioblastoma that has not responded to standard treatments. Eligibility: \- Individuals at least 18 years of age who have glioblastoma that has not responded to standard treatments. Design:

• Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected. Imaging studies and other tests will be used to study the tumor before the start of treatment.
• Participants will have 28-day (4-week) cycles of treatment.
• Participants will have TRC105 intravenously once a week. The first infusion will take about 4 hours. The length of time needed for the infusion may be slowly reduced if it is well tolerated.
• At the end of the first cycle (the first 4 weeks), the imaging studies will be repeated before continuing TRC105.
• Participants will take TRC105 for as long as the tumor does not grow and the side effects are not too severe. They will have imaging studies at the end of every cycle to evaluate the tumor.

Conditions

Glioblastoma Multiforme

Keywords

Glioblastoma; Anti-Angiogenesis; Radiotherapy; Malignant Glioma; Progression

Outcome Measures

Primary Outcomes (1)

• Radiographic Response Rate for Patients With Recurrent Glioblastoma Multiforme (GBM) Treated With TRC105.

  Response and progression will be evaluated by the Updated Response Assessment Criteria for High-Grade Gliomas developed by the Response Assessment in Neuro-Oncology Working Group (RANO). Complete response is complete disappearance of all enhancing measurable and non-measurable disease sustained for at least 4 weeks. Partial response is \>/=50% decrease compared with baseline in the sum of products of perpendicular diameters of all measurable enhancing lesions sustained for at least 4 weeks. Stable disease does not qualify for complete response, partial response, or progression. Progression is a \>/=25% increase in sum of the products of perpendicular diameters of enhancing lesions compared with the smallest tumor measurement obtained at baseline (if no decrease) or best response, on stable or increasing doses of corticosteroids,

  14 months

Secondary Outcomes (1)

• Number of Participants With Adverse Events

  5 months, 28 days

Study Arms (1)

TRC105 for Recurrent Glioblastoma

EXPERIMENTAL

Drug: TRC105

Interventions

TRC105 DRUG

Intravenous infusion.

TRC105 for Recurrent Glioblastoma

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically confirmed glioblastoma or gliosarcoma.
• Patients must have evidence for tumor progression by magnetic resonance imaging (MRI) or computed tomography (CT) scan. This scan should be performed within 14 days prior to registration and on a fixed dose of steroids for at least 5 days. If the steroid dose is increased between the date of imaging and registration a new baseline MR/CT is required. The same type of scan, ie, MRI or CT must be used throughout the period of protocol treatment for tumor measurement.
• Patients must have progressed after radiation therapy and must have an interval of greater
• Patients must have recovered from the toxic effects of prior therapy: 4 weeks from any investigational agent, 4 weeks from prior cytotoxic therapy, two weeks from vincristine, 6 weeks from nitrosoureas, 3 weeks from procarbazine administration, and 1 week for non-cytotoxic agents, e.g., interferon, tamoxifen, thalidomide, cis-retinoic acid, etc. Any questions related to the definition of non-cytotoxic agents should be directed to the Study Chair. All toxicities from prior therapies should be resolved to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) less than or equal to grade 1 (except for toxicities such as alopecia or vitiligo).
• Patients must be \> 18 years old. Because no dosing or adverse event data are currently available on the use of TRC105 in patients \< 18 years of age, children are excluded from this study, but will be eligible for future pediatric trials.
• Karnofsky performance status \> 60%
• Life expectancy of greater than 12 weeks.
• Patients must have normal organ and marrow function as defined below:
• leukocytes \> 3,000/microliter
• absolute neutrophil count \> 1,500/microliter
• platelets \> 100,000/microliter
• total bilirubin \< 1.5 times ULN institutional upper limit of normal
• Aspartate aminotransferase (AST) serum glutamic oxaloacetic transaminase (SGOT)/alanine aminotransaminase (ALT) serum glutamic pyruvic transaminase (SGPT) \< 2.5 times institutional upper limit of normal
• Prothrombin time (PT)/Partial thromboplastin time (PTT) \< 1.5 times institutional upper limit of normal
• creatinine \< 1.5 times ULN within normal institutional limits

You may not qualify if:

• Patients who are receiving any other investigational agents and/or who have received an investigational agent in the prior 28 days.
• Patients may not have had prior therapy with vascular endothelial growth factor (VEGF) receptor inhibitors.
• Patients with a history of peptic ulcer disease or erosive gastritis within the past 6 months, unless treated for the condition and complete resolution has been documented by esophagogastroduodenoscopy (EGD).
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to TRC105.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Exclude patients who have had angina, MI, symptomatic congestive heart failure (CHF), cerebral vascular accident (CVA), transient ischemic attack (TIA), arterial embolism, pulmonary embolism, deep vein thrombosis (DVT), percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass graft (CABG) within the last 6 months.
• Exclude patients with cardiac arrhythmias \> grade 2 in the last 28 days.
• Exclude patients with chronic hypertension, systolic BP \> 140 and/or diastolic BP \> 90 despite optimal treatment.
• Exclude human immunodeficiency virus (HIV)+ patients who have CD4 counts which are below the lower limit of normal for the institution
• Patients known to have a malignancy (other than their glioblastoma) that has required treatment in the last 12 months and/or is expected to require treatment in the next 12 months (except non-melanoma skin cancer or carcinoma in-situ in the cervix)
• Patients are not allowed to receive concurrent anti-coagulation, and may not have received thrombolytic or anticoagulant agents (except heparin or alteplase to maintain intravenous (IV) catheters) within 10 days prior to drug administration
• Serious or non-healing wound, ulcer or bone fracture
• History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months
• Evidence of bleeding diathesis or coagulopathy
• Patients with a history of hereditary hemorrhagic telangiectasia (HHT)

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ. Cancer statistics, 2007. CA Cancer J Clin. 2007 Jan-Feb;57(1):43-66. doi: 10.3322/canjclin.57.1.43.

  PMID: 17237035 BACKGROUND

• Yung WK, Mechtler L, Gleason MJ. Intravenous carboplatin for recurrent malignant glioma: a phase II study. J Clin Oncol. 1991 May;9(5):860-4. doi: 10.1200/JCO.1991.9.5.860.

  PMID: 1849986 BACKGROUND

• FRANKEL SA, GERMAN WJ. Glioblastoma multiforme; review of 219 cases with regard to natural history, pathology, diagnostic methods, and treatment. J Neurosurg. 1958 Sep;15(5):489-503. doi: 10.3171/jns.1958.15.5.0489. No abstract available.

  PMID: 13576192 BACKGROUND

MeSH Terms

Conditions

Glioblastoma; Glioma; Disease Progression

Interventions

carotuximab

Condition Hierarchy (Ancestors)

Astrocytoma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Dr. Joohee Sul
• Organization: National Cancer Institute

Joohee_Sul@nih.gov

301-402-6298

Study Officials

• Joohee Sul, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

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: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 26, 2013
• First Posted: January 29, 2013
• Study Start: December 1, 2012
• Primary Completion: February 1, 2014
• Study Completion: February 1, 2014
• Last Updated: October 7, 2015
• Results First Posted: May 12, 2014

Record last verified: 2015-10

Locations

US (1)