Repeat Radiation, Minocycline and Bevacizumab in Patients With Recurrent Glioma

NCT01580969 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: HCI55264
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

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, Progression Free Survival (PFS)-3, PFS-6, and effects on quality of life and cognition from repeat radiation and bevacizumab.

Conditions

Recurrent Glioma

Keywords

glioma

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Adverse Events

  Adverse Events were assessed from start of minocycline treatment (one day prior to start of radiation therapy) until 28 days following the end of radiation therapy. Adverse events were assessed using the Common Terminology for Adverse Events (CTCAE) version 4.0. Each event was assigned a grade (1-5), with lower grades indicating milder events. Events were categorized as severe (grade 3-4) or non-severe (grade 1-2). All adverse events were recorded, regardless of attribution to study treatment. Reported below are the number of patients who experienced any non-severe AE and the number of patients who experienced any severe AE. A full listing of AEs (severe and non-severe) are listed in the Adverse Events module of the Results section.

  From first dose of study treatment to 28 days following radiation therapy (7-8 weeks)

Secondary Outcomes (8)

• Progression Free Survival (PFS) at 3 Months

  From start of study treatment until 12 weeks after radiation therapy (15-16 weeks)

• Progression Free Survival (PFS) at 6 Months

  From start of study treatment until 26 weeks after radiation therapy (29-30 weeks)

• Tabulation of Tumor Best Responses

  From start of study treatment until 26 weeks after radiation therapy (29-30 weeks)

• Quality of Life Change Over Time

  From start of study treatment until 26 weeks after radiation therapy (29-30 weeks)

• Cognitive Change Over Time - DET

  From start of study treatment until 26 weeks after radiation therapy (29-30 weeks)

Study Arms (3)

Dose Level 0: 100 mg bid

EXPERIMENTAL

Patients receiving minocycline 100 mg bid, bevacizumab, and radiation therapy.

Drug: Bevacizumab; Drug: Minocycline; Radiation: Radiation

Dose Level 1: 200 mg bid

EXPERIMENTAL

Patients receiving minocycline 200 mg bid, bevacizumab, and radiation therapy.

Drug: Bevacizumab; Drug: Minocycline; Radiation: Radiation

Dose Level 2: 400 mg bid

EXPERIMENTAL

Patients receiving minocycline 400 mg bid, bevacizumab, and radiation therapy.

Drug: Bevacizumab; Drug: Minocycline; Radiation: Radiation

Interventions

Bevacizumab DRUG

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.

Also known as: Avastin

Dose Level 0: 100 mg bid; Dose Level 1: 200 mg bid; Dose Level 2: 400 mg bid

Minocycline DRUG

Minocycline will be given by mouth twice a day at the assigned dose level. Minocycline will be started on the day prior to radiation and continued until progression or intolerance.

Dose Level 0: 100 mg bid; Dose Level 1: 200 mg bid; Dose Level 2: 400 mg bid

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.

Dose Level 0: 100 mg bid; Dose Level 1: 200 mg bid; Dose Level 2: 400 mg bid

Eligibility Criteria

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

You may qualify if:

• Male or female patients ≥18 years old with a life expectancy of at least 8 weeks
• Radiographically proven recurrent (≥ first relapse), intracranial glioma
• Previous treatment with external beam radiation
• Radiographic progression on current or prior bevacizumab treatment
• 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.
• Karnofsky performance status of ≥50
• Adequate hematologic, hepatic, and renal function (absolute neutrophil count ≥1.0 x 109/L, Hgb \>9 g/dL, platelet count ≥50 x 109/L, aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤2.5x ULN, creatinine ≤1.5x ULN)
• Willing and able to provide written informed consent prior to any study related procedures and to comply with all study requirements
• Systolic blood pressure ≤ 160 mg Hg or diastolic pressure ≤ 90 mg Hg within 14 days prior to study registration
• Prothrombin time/international normalized ratio (PT INR) \< 1.4 for patients not on warfarin confirmed by testing within 14 days prior to study registration
• Patients on full-dose anticoagulants (e.g., warfarin or low molecular weight (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

You may not qualify if:

• Use of an investigational drug within 14 days or within 5 half-lives of teh investigational drug, whichever is shorter
• Progression within 3 months of previous radiation by Radiographic Assessment in Neurooncology (RANO) criteria
• History of Grade 2 (CTCAE v4) or greater acute intracranial hemorrhage
• A concurrent active cancer that requires non-surgical therapy (e.g. chemotherapy, radiation, adjuvant therapy).
• 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
• Women of child-bearing potential who are pregnant or breast feeding
• 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
• History of stroke, cerebral vascular accident (CVA) or transient ischemic attack within 6 months
• 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
• Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration
• 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

Sponsors & Collaborators

• University of Utah: lead

Study Sites (1)

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

MeSH Terms

Conditions

Glioma

Interventions

Bevacizumab; Minocycline; Radiation

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Physical Phenomena

Results Point of Contact

• Title: Josiah Hawks
• Organization: Huntsman Cancer Institute

Josiah.Hawks@hci.utah.edu

801-585-0601

Study Officials

• Adam Cohen, MD

  University of Utah

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 6, 2012
• First Posted: April 19, 2012
• Study Start: July 6, 2012
• Primary Completion: January 12, 2018
• Study Completion: May 15, 2018
• Last Updated: August 16, 2019
• Results First Posted: February 6, 2019

Record last verified: 2019-08

Locations

US (1)