Clinical trial NCT01580969: Repeat Radiation, Minocycline and Bevacizumab in Patients With Recurrent Glioma
Official title: A Phase 1b/2 Study of Repeat rAdiation, Minocycline, and Bevacizumab in Patients With Recurrent gliOma (RAMBO)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Recurrent Glioma
Keywords: glioma
Lead sponsor: University of Utah
Sponsor class: OTHER
First posted: 2012-04-19
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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 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, aspartate aminotransferase (AST)/alanine aminotransferase (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 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

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 Radiographic Assessment in Neurooncology (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

Primary outcomes:
measure: Number of Participants With Adverse Events
timeFrame: From first dose of study treatment to 28 days following radiation therapy (7-8 weeks)
Secondary outcomes:
measure: Progression Free Survival (PFS) at 3 Months
timeFrame: From start of study treatment until 12 weeks after radiation therapy (15-16 weeks)
measure: Progression Free Survival (PFS) at 6 Months
timeFrame: From start of study treatment until 26 weeks after radiation therapy (29-30 weeks)
measure: Tabulation of Tumor Best Responses
timeFrame: From start of study treatment until 26 weeks after radiation therapy (29-30 weeks)
measure: Quality of Life Change Over Time
timeFrame: From start of study treatment until 26 weeks after radiation therapy (29-30 weeks)
measure: Cognitive Change Over Time - DET
timeFrame: From start of study treatment until 26 weeks after radiation therapy (29-30 weeks)
measure: Cognitive Change Over Time - IDN
timeFrame: From start of study treatment until 26 weeks after radiation therapy (29-30 weeks)
measure: Cognitive Change Over Time - OCLT
timeFrame: From start of study treatment until 26 weeks after radiation therapy (29-30 weeks)
measure: Cognitive Change Over Time - GMLT
timeFrame: From start of study treatment until 26 weeks after radiation therapy (29-30 weeks)
Other outcomes:
Locations:
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute
state: Utah
Study officials:
affiliation: University of Utah
name: Adam Cohen, MD
role: PRINCIPAL_INVESTIGATOR
References: