Laser Interstitial Thermal Therapy and Lomustine in Treating Patients With Recurrent Glioblastoma or Anaplastic Astrocytoma
Condition: IDH Family Wildtype; Recurrent Anaplastic Astrocytoma; Recurrent Glioblastoma
MeSH terms: Glioblastoma; Astrocytoma; Recurrence
Intervention: Laser Interstitial Thermal Therapy; Lomustine
Intervention description: Undergo LITT; Given PO
Intervention MeSH terms: Lomustine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 7.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well laser interstitial thermal therapy and lomustine work in
      treating patients with glioblastoma or anaplastic astrocytoma that has come back. Using laser
      to heat the tumor cells may help to kill them. Drugs used in chemotherapy, such as lomustine,
      work in different ways to stop the growth of tumor cells, either by killing the cells, by
      stopping them from dividing, or by stopping them from spreading. Giving laser interstitial
      thermal therapy and lomustine may work better in treating patients with glioblastoma or
      anaplastic astrocytoma.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have histologically-proven, recurrent supratentorial grade IV
             glioblastoma (or grade III IDH-wildtype anaplastic astrocytoma), for which a complete
             surgical resection is unsafe due to location, shape, or size of the tumor. Diagnosis
             of recurrence will be established by biopsy and frozen section immediately prior to
             initiating LITT procedure. If findings on frozen section are not consistent with
             recurrence (glioblastoma or recurrent IDH-wildtype anaplastic astrocytoma), decision
             to proceed with LITT procedure will be at the discretion of the neurosurgeon (only
             patients with histologically-proven recurrent tumor will be evaluable for efficacy).

          -  All patients must sign an informed consent indicating that they are aware of the
             investigational nature of this study. Patients must have signed an authorization for
             the release of their protected health information. Patients must be registered prior
             to treatment on study.

          -  Patients must have a Karnofsky performance score (KPS) > 60.

          -  Patients must have received standard of care therapy with chemoradiation with
             temozolomide followed by adjuvant chemotherapy with temozolomide. Patients may have
             received one additional chemotherapy regimen (other than lomustine) in addition to
             adjuvant temozolomide prior to study entry (patients at either first or second
             recurrence are eligible).

          -  In the context of this clinical trial, a lesion suitable for LITT is single,
             enhancing, supratentorial, at least 2 cm from inner table of skull over the
             hemispheric convexity, and > 1 cm, but < 4 cm in cross-sectional dimension, including
             thalamic tumor (=< 3 cm).

          -  Patients must have stable cardiovascular, neurovascular and neurological status, and
             be considered surgical candidates, as determined by any relevant pre-operative
             assessments, at the neurosurgeon's discretion.

          -  Patients must not be receiving concurrent anti-tumor treatment and must have recovered
             from toxicity of prior treatment. Minimum interval required: 1) > 6 weeks following
             nitrosourea chemotherapy; 2) > 4 weeks after recovering from any non-nitrosourea drug
             or systemic investigational agent; 3) > 2 weeks after receiving any non-cytotoxic
             anti-tumor drug; 4) > 4 weeks after receiving radiation therapy (> 12 weeks following
             upfront concurrent chemoradiation); 5) > 2 weeks following Optune device use.

          -  Patients must not have previously undergone an intracranial LITT procedure.

          -  White blood cell (WBC) > 3,000/ul (performed within 14 days (+ 3 working days) prior
             to registration)

          -  Absolute neutrophil count (ANC) > 1,500/mm^3 (performed within 14 days (+ 3 working
             days) prior to registration)

          -  Platelet count of > 100,000/mm^3 (may be reached by transfusion) (performed within 14
             days (+ 3 working days) prior to registration)

          -  Hemoglobin > 10 gm/dl (may be reached by transfusion) (performed within 14 days (+ 3
             working days) prior to registration)

          -  Serum glutamic-oxaloacetic transaminase (SGOT) and bilirubin < 2 times upper limit of
             normal (ULN) (performed within 14 days (+ 3 working days) prior to registration)

          -  Creatinine < 1.5 mg/dL (performed within 14 days (+ 3 working days) prior to
             registration)

          -  Women of childbearing potential must have a negative B-Human chorionic gonadotropin
             (HCG) documented within 7 days prior to registration and must agree to practice
             adequate contraception as defined below. Non-childbearing potential (i.e.,
             physiologically incapable of becoming pregnant), includes any female who has had:

               -  A hysterectomy

               -  A bilateral oophorectomy

               -  A bilateral tubal ligation

               -  Is post-menopausal: Subjects not using hormone replacement therapy (HRT) must
                  have experienced total cessation of menses for >= 1 year and be greater than 45
                  years in age, OR, in questionable cases, have a follicle stimulating hormone
                  (FSH) value > 40 mIU/mL and an estradiol value < 40 pg/mL (< 140 pmol/L).

          -  Subjects using HRT must have experienced total cessation of menses for >= 1 year and
             be greater than 45 years of age OR have had documented evidence of menopause based on
             FSH and estradiol concentrations prior to initiation of HRT.

          -  Childbearing potential includes any female who has had a negative serum pregnancy test
             within 7 days of study registration, and agrees to use adequate contraception.
             Acceptable contraceptive methods, when used consistently and in accordance with both
             the product label and the instructions of the physician, are as follows:

               -  Complete abstinence from sexual intercourse for 14 days before starting
                  treatment, through the treatment, and for at least 1 month after the last dose of
                  temozolomide

               -  Oral contraceptive, either combined or progestogen alone. A second barrier method
                  is required during the first month of treatment with oral contraceptives

               -  Injectable progesterone

               -  Implants of levonorgestrel

               -  Estrogenic vaginal ring

               -  Percutaneous contraceptive patches

               -  Intrauterine device (IUD) or intrauterine system (IUS) with a documented failure
                  rate of less than 1% per year

               -  Male partner sterilization (vasectomy with documentation of azoospermia) prior to
                  the female subject's entry into the study, and this male is the sole partner for
                  that subject

               -  Double barrier method: condom and an occlusive cap (diaphragm or cervical/vault
                  caps) with a vaginal spermicidal agent (foam/gel/film/cream/suppository). Female
                  participants who are lactating should discontinue nursing prior to the first dose
                  of temozolomide and should refrain from nursing throughout the treatment period
                  and for 42 days following the last dose of lomustine.

        Exclusion Criteria:

          -  Patients must not have received prior treatment with bevacizumab.

          -  Patients must not have had prior treatment of glioblastoma with stereotactic
             radiosurgery, brachytherapy, or carmustine-impregnated wafers (Gliadel).

          -  Patients must not have symptoms attributed to mass effect of the tumor (despite
             corticosteroid treatment) that would be better treated with debulking surgery, or
             wherein surgical debulking in the first 30 days following LITT procedure would be
             anticipated for symptom management.

          -  Patients unable to undergo MRI are not eligible.

          -  Patients with progression of multifocal tumors or tumors involving the posterior fossa
             (brainstem and cerebellum) will be excluded, as will patients where the anticipated
             treatment margin will be within 5 mm of critical intracranial structures (e.g.,
             primary branches of cerebral vessels, dural sinuses, hypophysis or cranial nerves).

          -  Patients may not have undergone previous treatment with lomustine.

          -  Patients must not have any significant medical illnesses that in the investigator's
             opinion cannot be adequately controlled with appropriate therapy or would compromise
             the patient's ability to tolerate this therapy.

          -  Patients with a history of any other cancer (except non-melanoma skin cancer or
             carcinoma in-situ of the cervix), unless in complete remission and off of all therapy
             for that disease for a minimum of 3 years are ineligible.

          -  Patients must not have active infection or serious intercurrent medical illness.

          -  Patients must not be pregnant/breast feeding and must agree to practice adequate
             contraception.

          -  Patients must not have uncontrolled hypertension (systolic >180 mm hg or diastolic >
             100 mg Hg), angina pectoris, cardiac dysrhythmia, or recent (within 6 weeks)
             intracranial hemorrhage.