Clinical Trials /

Laser Interstitial Thermal Therapy and Lomustine in Treating Patients With Recurrent Glioblastoma or Anaplastic Astrocytoma

NCT03022578

Description:

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.

Related Conditions:
  • Anaplastic Astrocytoma
  • Glioblastoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of Laser Interstitial Thermal Therapy (LITT) in Recurrent Glioblastoma
  • Official Title: Phase II Study of Laser Interstitial Thermal Therapy (LITT) in Recurrent Glioblastoma

Clinical Trial IDs

  • ORG STUDY ID: 2016-0443
  • NCT ID: NCT03022578

Conditions

  • Malignant Neoplasms of Eye Brain and Other Parts of Central Nervous System
  • Glioblastoma
  • Anaplastic Astrocytoma

Interventions

DrugSynonymsArms
LomustineCeeNU, CCNULaser Interstitial Thermal Therapy (LITT) + Lomustine

Purpose

Participant is being asked to take part in this study because they have glioblastoma or anaplastic astrocytoma (AA) that has relapsed (come back) after treatment and the study doctor thinks that it is in their best interest to receive chemotherapy for the disease. Additionally, the study doctor thinks it may be in participant's best interest to also have a surgical procedure called laser interstitial thermal therapy (LITT). LITT is a minimally invasive (using small incisions) surgery method that uses lasers to destroy tumor cells. For the procedure, the study doctor uses the NeuroBlate system to perform LITT in combination with MRIs and software models to focus the lasers on affected brain cells. The goal of this clinical research study is to learn if the NeuroBlate system in combination with lomustine can help to control glioblastoma or anaplastic astrocytoma (AA) that has returned after treatment. The safety of the combination will also be studied.

Detailed Description

      Study Drug/Procedure Administration:

      If participant is found to be eligible to take part in this study, they will be scheduled to
      have the LITT procedure. An MRI will be performed the day before the procedure to produce
      images of participant's brain to direct the study doctor to the areas that should be
      treated. The LITT procedure will then be performed the next day. Participant will sign a
      separate consent form for the LITT procedure that explains this procedure and its risks in
      more detail.

      Participant will then receive standard of care hospitalization after surgery. Participant
      will have an MRI within 48 hours after the procedure to check the status of the disease.

      Participant will have 14 - 35 days for recovery from the LITT procedure. Participant will
      not take lomustine during this period. After the recovery period, participant will take
      lomustine by mouth on Day 1 of every 42-day cycle.

      Participant should take lomustine by mouth on an empty stomach before bed (2 hours after or
      1 hour before food).

      Length of Treatment:

      Participant will take lomustine for up to 6 cycles. Participant will no longer be able to
      take the study drug if the disease gets worse, if they have intolerable side effects, or if
      they are unable to follow study directions.

      Participation in the study will be over after follow-up.

      Study Visits:

      On the day of the LITT procedure:

        -  Participant will have a physical exam, including a neurological exam.

        -  Participant will have MRI scans to help the surgeon perform LITT.

        -  Blood (about 2 teaspoons) will be drawn for biomarker testing. Biomarkers are found in
           the blood and tissue and may be related to participant's reaction to the study drugs.

        -  Tumor tissue will be collected to confirm the diagnosis and for biomarker testing
           during the LITT procedure.

      Within 2 days after the LITT procedure, participant will have an MRI.

      About 14 days after the LITT procedure:

        -  Participant will have a physical exam, including a neurological exam.

        -  Blood (about 2 teaspoons) will be drawn for routine tests. If participant can become
           pregnant, this will also include a pregnancy test.

        -  Participant will complete the questionnaire about your quality of life.

        -  Participant will have an MRI.

      When participant begins receiving lomustine, they will have study visits in 42-day cycles.

      On Day 1 of each cycle:

        -  Participant will have a physical exam, including a neurological exam.

        -  Blood (about 2 teaspoons) will be drawn for routine test. If participant can become
           pregnant, this will also include a pregnancy test.

        -  Participant will complete the questionnaire about their quality of life.

        -  You will have an MRI.

      On Days 15 and 29 of each cycle, blood ( about 2 teaspoons) will be drawn for routine tests.

      At any time during the study, extra tests may be performed if the doctor thinks they are
      needed. The study doctor will tell participant more about any extra tests.

      End-of-Study Visit:

      About 6 weeks after stopping the study drug:

        -  Participant will have a physical and neurological exam.

        -  Participant will complete the questionnaire about their quality of life.

        -  Participant will have an MRI scan.

      Follow-Up:

      Every 3 months after participant's last dose of the study drug, the study staff will call
      and ask how they are feeling. This call should take about 5-10 minutes.

      If participant stops the study drug for any reason other than the disease getting worse,
      they will visit the clinic every 3 months unless the disease gets worse. At these visits:

        -  Participant will have a physical exam, including a neurological exam.

        -  Participant will complete the questionnaire about their quality of life.

        -  Participant will have an MRI.

      This is an investigational study. The NeuroBlate system is FDA approved and commercially
      available for different types of brain surgery. Lomustine is FDA approved and commercially
      available for the treatment of brain tumors. LITT using the NeuroBlate System in combination
      with lomustine for the treatment of glioblastoma is investigational.

      The study doctor can describe how the study drug and procedure are designed to work.

      Up to 37 participants will be enrolled in this study. All will take part at MD Anderson.
    

Trial Arms

NameTypeDescriptionInterventions
Laser Interstitial Thermal Therapy (LITT) + LomustineExperimentalParticipants undergo thermal ablation of tumor utilizing the LITT procedure. 14-35 days following the LITT procedure participants initiate treatment with Lomustine. Lomustine administered by mouth at 90 mg/m2 on Day 1 for the first six week cycle. The dose of Lomustine may be increased to 110 mg/m2 starting with the second six week cycle, at the treating physician's discretion, as long as patient has not required dose modification for toxicity. Quality of life questionnaires completed at baseline, 14 days after LITT procedure, on Day 1 of each Lomustine cycle, 6 weeks after Lomustine stopped, and every 3 months during follow up.
  • Lomustine

Eligibility Criteria

        Inclusion Criteria:

          1. 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).

          2. 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.

          3. Patients must be >/= 18 years old.

          4. Patients must have a Karnofsky Performance Score (KPS) >60.

          5. 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).

          6. 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).

          7. 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.

          8. 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.

          9. Patients must not have previously undergone an intracranial LITT procedure. Patients
             must have adequate bone marrow function (white blood cell (WBC) > 3,000/µl, ANC >
             1,500/mm3, platelet count of > 100,000/mm3, and hemoglobin > 10 gm/dl), adequate
             liver function (SGOT and bilirubin < 2 times ULN), and adequate renal function
             (creatinine < 1.5 mg/dL) before starting therapy. These tests must be performed
             within 14 days (+ 3 working days) prior to registration. Eligibility level for
             hemoglobin and platelets may be reached by transfusion.

         10. Women of childbearing potential must have a negative B-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: 1. A hysterectomy 2. A bilateral
             oophorectomy 3. A bilateral tubal ligation 4. 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 < 40pg/mL
             (<140 pmol/L).

         11. (10. continued) 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.

         12. (11. continued) 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: 1. 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. 2. Oral contraceptive, either combined or progestogen alone. A second
             barrier method is required during the first month of treatment with oral
             contraceptives.

         13. (12. continued) 3. Injectable progesterone 4. Implants of levonorgestrel. 5.
             Estrogenic vaginal ring. 6. Percutaneous contraceptive patches. 7. Intrauterine
             device (IUD) or intrauterine system (IUS) with a documented failure rate of less than
             1% per year. 8. 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. 9. 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:

          1. Patients must not have received prior treatment with bevacizumab.

          2. Patients must not have had prior treatment of glioblastoma with stereotactic
             radiosurgery, brachytherapy, or carmustine-impregnated wafers (Gliadel).

          3. 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.

          4. Patients unable to undergo MRI are not eligible.

          5. 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).

          6. Patients may not have undergone previous treatment with lomustine.

          7. 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.

          8. 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.

          9. Patients must not have active infection or serious intercurrent medical illness.

         10. Patients must not be pregnant/breast feeding and must agree to practice adequate
             contraception.

         11. 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Disease Control Rate
Time Frame:6 months
Safety Issue:
Description:Disease control rate at defined as the percentage of evaluable patients that have at least stable disease or better at 6 months after the LITT procedure. RANO criteria used to determine progression.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:M.D. Anderson Cancer Center

Trial Keywords

  • Malignant Neoplasms of Eye Brain and Other Parts of Central Nervous System
  • Glioblastoma
  • Anaplastic Astrocytoma
  • AA
  • Laser interstitial thermal therapy
  • LITT
  • Lomustine
  • CeeNU
  • CCNU

Last Updated

April 19, 2017