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Fractionated Stereotactic Radiosurgery With Concurrent Bevacizumab for Brain Metastases: A Phase I Dose-escalation Trial

This study is currently recruiting participants.
Verified August 2017 by National Taiwan University Hospital
Sponsor:
ClinicalTrials.gov Identifier:
NCT02672995
First Posted: February 3, 2016
Last Update Posted: August 18, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
National Taiwan University Hospital
  Purpose
The investigators propose a new treatment strategy of fractionated stereotactic radiosurgery with concurrent bevacizumab for brain metastases. This phase I dose-escalation study is to establish the feasibility of this strategy and find the recommended doses.

Condition Intervention Phase
Brain Neoplasm Radiation: Fractionated stereotactic radiosurgery Drug: bevacizumab Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Fractionated Stereotactic Radiosurgery With Concurrent Bevacizumab for Brain Metastases: A Phase I Dose-escalation Trial

Resource links provided by NLM:


Further study details as provided by National Taiwan University Hospital:

Primary Outcome Measures:
  • Maximum tolerated dose [ Time Frame: 4 months ]
    The maximum tolerated dose of fractionated stereotactic radiosurgery with concurrent bevacizumab for brain metastases.


Secondary Outcome Measures:
  • Response rate [ Time Frame: 4 months ]
    Response rate

  • Time to progression [ Time Frame: 4 months ]
    Time to progression

  • The incidence of radiation-induced adverse effects [ Time Frame: 4 months ]
    The incidence of radiation-induced adverse effects


Estimated Enrollment: 36
Anticipated Study Start Date: January 2018
Estimated Study Completion Date: December 2018
Estimated Primary Completion Date: December 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Single arm dose-escalation

Fractionated stereotactic radiosurgery:

Group 1: tumors 1.5~2.5 cm in diameter Dose level 1: 21 Gy in 3 fractions Dose level 2: 24 Gy in 3 fractions Dose level 3: 27 Gy in 3 fractions Group 2: tumors 2.5~3.5 cm in diameter Dose level 1: 18 Gy in 3 fractions Dose level 2: 21 Gy in 3 fractions Dose level 3: 24 Gy in 3 fractions Three fractions will be given in one week with at least 1 day break.

Concurrent bevacizumab:

Bevacizumab 7.5 mg/kg will be given one day before the first fraction of radiosurgery and 2 weeks after the first dose of bevacizumab.

Radiation: Fractionated stereotactic radiosurgery

Fractionated stereotactic radiosurgery:

Group 1: tumors 1.5~2.5 cm in diameter Dose level 1: 21 Gy in 3 fractions Dose level 2: 24 Gy in 3 fractions Dose level 3: 27 Gy in 3 fractions Group 2: tumors 2.5~3.5 cm in diameter Dose level 1: 18 Gy in 3 fractions Dose level 2: 21 Gy in 3 fractions Dose level 3: 24 Gy in 3 fractions Three fractions will be given in one week with at least 1 day break.

Other Name: Fractionated SRS
Drug: bevacizumab

Concurrent bevacizumab:

Bevacizumab 7.5 mg/kg will be given one day before the first fraction of radiosurgery and 2 weeks after the first dose of bevacizumab.

Other Name: Avastin

Detailed Description:

For each group (two groups according to tumor size), the design proceeds with cohorts of three patients, with the first cohort treated at a starting dose. If none of the three patients in a cohort experiences a dose-limiting toxicity (DLT), the next cohort with three patients will be treated at the next higher dose level. If one of the first three patients experiences a dose-limiting toxicity, the next cohort will be treated at the same dose level. The dose escalation continues until at least two patients among a cohort of three to six patients experience DLTs and the maximum tolerated dose (MTD) will be the dose level just below. If the highest planned dose was achieved without two patients experiencing DLTs, the MTD will be that dose level.

The DLT is defined as grade 4 or above toxicities according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 within 4 months after stereotactic radiosurgery (SRS):

Grade 4 central nervous system necrosis (life-threatening consequences; urgent intervention indicated) Grade 4 sensory or motor neuropathy (life-threatening consequences; urgent intervention indicated) Grade 4 hemorrhage (life-threatening consequences; urgent intervention indicated) or Grade 4 thromboembolic event (life-threatening consequences such as pulmonary embolism, cerebrovascular event, arterial insufficiency; hemodynamic or neurologic instability; urgent intervention indicated) Grade 4 hypertension (life-threatening consequences such as malignant hypertension, transient or permanent neurologic deficit, hypertensive crisis; urgent intervention indicated)

Study treatment:

Fractionated stereotactic radiosurgery:

Group 1: tumors 1.5~2.5 cm in diameter Dose level 1: 21 Gy in 3 fractions Dose level 2: 24 Gy in 3 fractions Dose level 3: 27 Gy in 3 fractions Group 2: tumors 2.5~3.5 cm in diameter Dose level 1: 18 Gy in 3 fractions Dose level 2: 21 Gy in 3 fractions Dose level 3: 24 Gy in 3 fractions Three fractions will be given in one week with at least 1 day break.

Concurrent bevacizumab:

Bevacizumab 7.5 mg/kg will be given one day before the first fraction of radiosurgery and 2 weeks after the first dose of bevacizumab.

  Eligibility

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   20 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria

To be eligible for inclusion, patients must fulfill the following criteria:

  1. Patients with a histologic diagnosis of non-hematopoietic malignancy and radiographic evidence of measurable brain metastases (1.5~3.5 cm).
  2. The number of brain metastases receiving fractionated SRS: ≤3.
  3. No evidence of leptomeningeal metastasis on gadolinium-enhanced MRI within 30 days prior registration.
  4. Age ≥ 20 years.
  5. Karnofsky Performance Status ≥ 60.
  6. Life expectancy of ≥ 4 months.
  7. Women of childbearing potential and male participants must practice adequate contraception.
  8. Patients must be able to comply with the study protocol and follow-up schedules and provide study-specific informed consent.

Exclusion criteria Patients fulfill any of the following criteria will be excluded from this trial

  1. Serum creatinine > 2.0 mg/dL within 30 days prior registration
  2. Contraindication to magnetic resonance (MR) imaging such as implanted metal devices or foreign bodies, severe claustrophobia
  3. Patients with evidence of bleeding diathesis or coagulopathy, international normalized ratio (INR) >1.5
  4. Patients who require the use of warfarin sodium > 1 mg
  5. Patients with active GI ulcers, GI bleeding, or active inflammatory bowel disease
  6. Patients with clinically significant cardiac disease (e.g., uncontrolled hypertension [blood pressure of >160/90 mmHg on medication], history of myocardial infarction or unstable angina within 12 months of registration), New York Heart Association (NYHA) Class II or greater congestive heart failure, unstable symptomatic arrhythmia requiring medication (subjects with chronic atrial arrhythmia, i.e., atrial fibrillation or paroxysmal supraventricular tachycardia) are not eligible
  7. Patients with a history of aneurysms, cerebrovascular accident (CVA) and arteriovenous malformations
  8. Patients with arterial thromboembolic events, including transient ischemic attack (TIA), or clinically significant peripheral artery disease within 6 months of registration
  9. Patients with serious, non-healing wound, ulcer, or current healing fracture
  10. Patients with a history of any type of fistula (vesicovaginal, gastrointestinal, etc) or gastrointestinal perforation
  11. Severe, active comorbidities which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and adverse events of the protocol, or limit compliance with study requirements, defined as follows:

    1. Uncontrolled active infection requiring intravenous antibiotics at the time of registration
    2. Transmural myocardial infarction ≤ 6 months prior to registration
    3. Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
    4. Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration
    5. Uncontrolled psychiatric disorder
  12. Will receive any other investigational agent or chemotherapy and/or target therapies during SRS
  13. Women of childbearing potential and male participants who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the radiation treatment involved in this study may be significantly teratogenic
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02672995


Contacts
Contact: Chia-Chun Wang, MD chiachun@ntuh.gov.tw
Contact: Feng-Ming Hsu

Locations
Taiwan
National Taiwan University Hospital Recruiting
Taipei, Taiwan, 100
Contact: Chia-Chun Wang       chiachun@ntuh.gov.tw   
Sponsors and Collaborators
National Taiwan University Hospital
Investigators
Principal Investigator: Chia-Chun Wang National Taiwan University Hospital
  More Information

Responsible Party: National Taiwan University Hospital
ClinicalTrials.gov Identifier: NCT02672995     History of Changes
Other Study ID Numbers: 201511005MINB
First Submitted: January 28, 2016
First Posted: February 3, 2016
Last Update Posted: August 18, 2017
Last Verified: August 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by National Taiwan University Hospital:
stereotactic radiosurgery,Bevacizumab

Additional relevant MeSH terms:
Brain Neoplasms
Brain Diseases
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Neoplasms
Central Nervous System Diseases
Nervous System Diseases
Bevacizumab
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antineoplastic Agents