TRC105 for Recurrent Glioblastoma

This study has been terminated.
(Study was terminated due to poor accrual.)
Sponsor:
Information provided by (Responsible Party):
Joohee Sul, M.D., National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT01778530
First received: January 26, 2013
Last updated: May 12, 2014
Last verified: May 2014
  Purpose

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.

Condition Intervention Phase
Glioblastoma Multiforme
Drug: TRC105
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2 Study of TRC105 in Patients With Recurrent Glioblastoma (GBM)

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Radiographic Response Rate for Patients With Recurrent Glioblastoma Multiforme (GBM) Treated With TRC105. [ Time Frame: 14 months ] [ Designated as safety issue: No ]
    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,


Secondary Outcome Measures:
  • Number of Participants With Adverse Events [ Time Frame: 5 months, 28 days ] [ Designated as safety issue: Yes ]
    Here is the number of participants with adverse events. For details, see the adverse event module.


Enrollment: 2
Study Start Date: December 2012
Study Completion Date: February 2014
Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: TRC105 for Recurrent Glioblastoma Drug: TRC105
Intravenous infusion.

  Show Detailed Description

  Eligibility

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

OR

--creatinine clearance > 60 glomerular filtration rate for patients with creatinine

levels above institutional normal.

  • hemoglobin of > 9grams/deciliter without transfusion support in the past 28 days

    • Patients must not have any significant medical illnesses that, in the investigators opinion, cannot be adequately controlled with appropriate therapy or would compromise the patients ability to tolerate this therapy
    • Patients having undergone recent resection of recurrent or progressive tumor will be eligible as long as all of the following conditions apply:
  • They have recovered from the effects of surgery.
  • They should have residual disease following resection of recurrent tumor.

To best assess the extent of residual disease post-operatively, a computed tomography (CT)/ magnetic resonance imaging (MRI) should be done:

no later than 96 hours in the immediate post-operative period and

  • at least 4 weeks post-operatively, and
  • within 14 days of registration, and
  • on a steroid dosage that has been stable for at least 5 days.

If the steroid dose is increased between the date of imaging and registration, a new baseline MRI/CT is required on a stable steroid dosage for at least 5 days.

  • The effects of TRC105 on the developing human fetus are unknown. For this reason and because antiangiogenic agents are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of TRC105 administration.
  • Patients must have the ability to understand and the willingness to sign a written informed consent document.
  • A baseline 12 lead electrocardiogram (ECG) to be performed within 2 weeks of trial

EXCLUSION CRITERIA

  • 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)
  • Pregnant women are excluded from this study because TRC105 and antiangiogenic agents with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with TRC105, breastfeeding should be discontinued if the mother is treated with TRC105.
  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: NCT01778530

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
Investigators
Principal Investigator: Joohee Sul, M.D. National Cancer Institute (NCI)
  More Information

Publications:
Responsible Party: Joohee Sul, M.D., Principal Investigator, National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier: NCT01778530     History of Changes
Obsolete Identifiers: NCT01757652
Other Study ID Numbers: 130048, 13-C-0048
Study First Received: January 26, 2013
Results First Received: April 10, 2014
Last Updated: May 12, 2014
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Keywords provided by National Institutes of Health Clinical Center (CC):
Glioblastoma
Anti-Angiogenesis
Radiotherapy
Malignant Glioma
Progression

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 31, 2014