This pilot clinical trial studies magnetic resonance imaging (MRI)-guided laser surgery (MLA) and doxorubicin hydrochloride in treating patients with recurrent glioblastoma multiforme. The blood brain barrier (BBB) is a separation of circulating blood from the tissue of the central nervous system, preventing substances in the blood from entering the brain. MLA disrupts the BBB around the tumor which may allow cancer-killing substances to be carried directly to the tumor and the surrounding area. Using MLA prior to chemotherapy may result in a greater concentration of drug in the tumor to kill the cancer cells while limiting side effects.

Evaluate imaging techniques (MRI) and blood tests (biomarkers) to help figure out the best time for chemotherapy to be initiated after the blood brain barrier is disrupted, as it is immediately following a procedure like MRI-guided laser ablation (MLA-Monteris Neuroblate).

Inclusion Criteria - Arms B and C:

• Histologically confirmed GBM; rare GBM variants, secondary GBM, and suspected secondary GBM are allowed.

• Unequivocal evidence of tumor progression by magnetic resonance imaging (MRI) scan.

• There must be an interval of at least 12 weeks from the completion of radiotherapy to study registration except if there is unequivocal evidence for tumor recurrence per RANO criteria. When the interval is less than 12 weeks from the completion of radiotherapy, the use of PET scan is allowed to differentiate between unequivocal evidence of tumor recurrence and pseudoprogression.

• Candidate for MLA based on size, location, and shape of the recurrent tumor as determined by the performing neurosurgeon

• At least 18 years of age.

• Karnofsky performance status ≥ 60%.

• Scheduled for MRI-guided Laser Ablation (MLA).

• Normal left ventricular ejection fraction on MUGA or echocardiogram within the past 1 year prior to registration for patients with history of congestive heart failure and/or coronary disease requiring medications other than aspirin, or known prior exposure to anthracycline chemotherapy.

• Adequate bone marrow and hepatic function as defined below (must be within 7 days of MLA):

  • Absolute neutrophil count (ANC) ≥ 1500/mcl (G-CSF is allowed)
  • Platelets ≥ 100,000/mcl
  • Hemoglobin ≥ 9 (pRBC transfusion +/- ESA are allowed)
  • ALT ≤ 3 x ULN
  • AST ≤ 3 x ULN
  • ALP ≤ 3 x ULN. If ALP is > 3 x ULN, GGT must be checked and be ≤ 3 x ULN.
  • Bilirubin ≤ 2 x ULN

• At the time of registration, patient must have recovered from the toxic effects of prior therapy to no more than grade 1 toxicity.

• At the time of registration, patient must be at least 2 weeks from prior vincristine, 3 weeks from prior procarbazine, and 4 weeks from other prior cytotoxic chemotherapy.

• Women of childbearing 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 participating in this study, she must inform her treating physician immediately.

• Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).

Exclusion Criteria - Arms B and C:

• Prior treatment with doxorubicin and/or bevacizumab.
• Prior treatment with Gliadel wafer is allowed if it has been at least 3 months from placement.
• Previous treatment with complete cumulative doses of daunorubicin, idarubicin, and/or other anthracyclines and anthracenediones that is equivalent to a total dose of 240 mg/m2 doxorubicin.
• More than 2 prior relapses.
• Currently receiving any other investigational agents that are intended as treatments of GBM.
• A history of allergic reactions attributed to compounds of similar chemical or biologic composition to doxorubicin or other agents used in the study.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, recent heart attack within the previous 12 months or severe heart problems, or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant and/or breastfeeding. Premenopausal women must have a negative serum pregnancy test within 14 days of study entry.
• Inability to undergo MRI due to personal and medical reasons.
• Known history of HIV or autoimmune diseases requiring immunosuppressant drugs.