Repeat Radiation, Minocycline and Bevacizumab in Patients With Recurrent Glioma (RAMBO)

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by University of Utah
Sponsor:
Information provided by (Responsible Party):
University of Utah
ClinicalTrials.gov Identifier:
NCT01580969
First received: March 6, 2012
Last updated: July 2, 2014
Last verified: July 2014
  Purpose

The primary objective of step 1 is the rate of adverse events of minocycline and bevacizumab during reirradiation and of step 2 is the response rate to bevacizumab, reirradiation, and minocycline. The secondary objectives are the response rate, PFS-3, PFS-6, and effects on quality of life and cognition from repeat radiation and bevacizumab.


Condition Intervention Phase
Recurrent Glioma
Drug: Bevacizumab
Drug: Minocycline
Radiation: Radiation
Phase 1
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 1b/2 Study of Repeat rAdiation, Minocycline, and Bevacizumab in Patients With Recurrent gliOma (RAMBO)

Resource links provided by NLM:


Further study details as provided by University of Utah:

Primary Outcome Measures:
  • Rate of Adverse Events [ Time Frame: 30 months ] [ Designated as safety issue: Yes ]
    Rate of adverse events of minocycline and bevacizumab during reirradiation

  • Response rate [ Time Frame: 30 months ] [ Designated as safety issue: No ]
    Response rate to bevacizumab, reirradiation, and minocycline


Secondary Outcome Measures:
  • Quality of Life [ Time Frame: 30 months ] [ Designated as safety issue: No ]
    Effects on quality of life from repeat radiation and bevacizumab

  • Cognitive effects [ Time Frame: 30 months ] [ Designated as safety issue: No ]
    Effects on cognition from repeat radiation and bevacizumab


Estimated Enrollment: 18
Study Start Date: July 2012
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: All patients
All patients enrolled in study.
Drug: Bevacizumab
This is an open-label, multi-agent design. Bevacizumab will be administered in accordance with the FDA-approved dose for gliomas, 10mg/kg IV every 2 weeks. Bevacizumab will be continued every two weeks as long as tolerated. One cycle of bevacizumab will be 28 days, with treatments on day1 and day 15. Blood pressure, CBC, CMP, and urine protein level, either by UA or urine protein/creatinine ratio will be checked at the beginning of each cycle.
Other Name: Avastin
Drug: Minocycline
Minocycline will be given by mouth twice a day starting at about half of the monotherapy maximal tolerated dose, 100 mg PO BID. Minocycline will be started on the day prior to radiation and continued until progression or intolerance. During the combined radiation, minocycline, and bevacizumab treatment, patients will be seen weekly with a CBC, CMP, and adverse event monitoring.
Radiation: Radiation
Radiation planning will be individualized by the radiation oncologist based on the location of the current radiation field relative to prior radiation doses. The length and fractionation will be determined individually by the radiation oncologist.

Detailed Description:

After providing informed consent, patients will undergo screening for eligibility to participate in the study. Screening will start within 21 days prior to dosing.

Subjects will have an MRI within 21 days of starting radiation. QOL and cognition measures will be performed within 21 days of starting radiation. Radiation will be given with parameters determined on an individual basis by the radiation oncologist. Bevacizumab will be continued at 10mg/kg IV every 2 weeks. Minocycline will be given twice a day starting at 100mg PO BID. MRI, QOL, and cognitive tests will be obtained 1, 3 and 6 months after the end of radiation.

  Eligibility

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

Inclusion Criteria:

  1. Male or female patients ≥18 years old with a life expectancy of at least 8 weeks
  2. Radiographically proven recurrent (≥ first relapse), intracranial glioma
  3. Previous treatment with external beam radiation
  4. Radiographic progression on current or prior bevacizumab treatment
  5. Women of child-bearing potential must have a negative pregnancy test within 7 days of initiation of dosing and must agree to use an acceptable method of birth control while on study drug and for 3 months after the last dose. Women of non-childbearing potential may be included if they are either surgically sterile or have been postmenopausal for ≥1 year. Men of child-bearing potential must also agree to use an acceptable method of birth control while on study drug, and for 3 months after the last dose.
  6. Karnofsky performance status of ≥50
  7. Adequate hematologic, hepatic, and renal function (absolute neutrophil count ≥1.0 x 109/L, Hgb >9 g/dL, platelet count ≥50 x 109/L, AST/ALT ≤2.5x ULN, creatinine ≤1.5x ULN)
  8. Willing and able to provide written informed consent prior to any study related procedures and to comply with all study requirements
  9. Systolic blood pressure ≤ 160 mg Hg or diastolic pressure ≤ 90 mg Hg within 14 days prior to study registration
  10. Prothrombin time/international normalized ratio (PT INR) < 1.4 for patients not on warfarin confirmed by testing within 14 days prior to study registration
  11. Patients on full-dose anticoagulants (e.g., warfarin or LMW heparin) must have no active bleeding or pathological condition that carries a high risk of bleeding, and must be on a stable dose of oral anticoagulant or on a stable dose of low molecular weight heparin

Exclusion Criteria:

  1. Use of an investigational drug within 14 days or within 5 half-lives of teh investigational drug, whichever is shorter
  2. Progression within 3 months of previous radiation by RANO criteria
  3. History of Grade 2 (CTCAE v4) or greater acute intracranial hemorrhage
  4. A concurrent active cancer that requires non-surgical therapy (e.g. chemotherapy, radiation, adjuvant therapy).
  5. Patients with serious illnesses, uncontrolled infection, medical conditions, or other medical history including abnormal laboratory results, which in the investigator's opinion would be likely to interfere with a patient's participation in the study, or with the interpretation of the results
  6. Women of child-bearing potential who are pregnant or breast feeding
  7. Unstable angina and/or congestive heart failure in the last 6 months, transmural myocardial infarction within the last 6 months, New York Heart Association grade II or higher congestive heart failure requiring hospitalization within 12 months prior to registration, evidence of recent myocardial infarction by EKG performed within 14 days of registration, serious or inadequately controlled cardiac arrhythmia, significant vascular and peripheral vascular disease, evidence of bleeding diathesis or coagulopathy
  8. History of stroke, cerebral vascular accident (CVA) or transient ischemic attack within 6 months
  9. Serious or non-healing wound, ulcer, or bone fracture or history of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to registration, with the exception of the craniotomy for tumor resection
  10. Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration
  11. Active connective tissue disorders, such as lupus or scleroderma, that in the opinion of the treating physician may put the patient at high risk for radiation toxicity
  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: NCT01580969

Contacts
Contact: Britney Hall 801-213-4323 britney.hall@hci.utah.edu
Contact: Amiee Maxwell 801-587-5562 amiee.maxwell@hci.utah.edu

Locations
United States, Utah
Huntsman Cancer Institute Recruiting
Salt Lake City, Utah, United States, 84112
Sponsors and Collaborators
University of Utah
  More Information

No publications provided

Responsible Party: University of Utah
ClinicalTrials.gov Identifier: NCT01580969     History of Changes
Other Study ID Numbers: HCI55264
Study First Received: March 6, 2012
Last Updated: July 2, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of Utah:
glioma

Additional relevant MeSH terms:
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Bevacizumab
Minocycline
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses
Anti-Bacterial Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on September 30, 2014