Physician

Hugh Moulding, MD

Study Coordinator

Jillian Timer, RN, BSN
484-503-4156

Jillian.timer@sluhn.org

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Treatment Agent: 5-ALA (Gliolan®)

Synopsis: The purpose of this study is to determine the safety and utility of 5-aminolevulinic acid (ALA) (Gliolan is the name brand for 5-ALA) for identifying your tumor during surgery. Gliolan® (5-ALA) is not FDA approved at this time. Sometimes this can be difficult because the tumor can look like normal brain. In some brain tumors, Gliolan® (5-ALA) can make the tumors glow red under blue light. This may make it easier for your doctor to visualize the tumor from your brain and is known as fluorescence-guided surgery. In multiple studies, Gliolan® (5-ALA)-induced tissue fluorescence has been shown to correlate with malignant tumor. The purpose of this study is to:

• to study if Gliolan® (5-ALA) can predict the presence of tumor during the surgery for tumor resection (surgical removal of tumor).
• confirm Gliolan® (5-ALA) is safe to use with minimal or no side-effects.

During surgical resection of your brain tumor with fluorescence-guidance, after administration of Gliolan, multiple different portions of your brain tumor will be sampled and studied further after tissue banking at the Icahn School of Medicine at Mount Sinai. In addition to standard pathologic examination, the tumor samplings will be studied further for various genetic and protein expression changes localized to different regions of your tumor.

You may qualify to take part in this research study because you may have a brain tumor type that may be visualized in the operating room by fluorescence-guidance after Gliolan® (5-ALA) administration. The manufacturer of the 5-ALA is Photonamic Inc., which is based in Germany and supplies the Gliolan® (5-ALA) to St. Luke’s University Health Network.

The study also plans to assess:

• The safety of ABT-414
• How your body handles this new drug with the combination

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• Subjects included must have an MRI documenting a primary brain tumor for which resection is indicated and has been planned. These patients will include those with newly diagnosed or recurrent malignant gliomas. Standard criteria for diagnosis will include a distinct ring-like pattern of contrast enhancement with thick irregular walls on MRI for patients with a presumed newly diagnosed malignant glioma.
• Age 18-80.
• Karnofsky > 60%.
• Subjects must have normal organ and marrow function as defined below:

Leukocytes >3,000/mL Platelets >100,000/mL Total bilirubin below upper limit of normal AST (SGOT)/ALT (SGPT) <2.5 x="" institutional="" upper="" limit="" of="" normal="" creatinine="" below="" upper="" limit="" of="" normal="" or="" creatinine="" clearance="">60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal.

• The effects of 5-aminolevulinic Acid (5-ALA) on the developing human fetus are unknown. For this reason, women of child-bearing 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. A pregnancy test will be performed for all women of childbearing ability prior to surgery (see Exclusion Criteria below). Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
• Ability to understand and the willingness to sign a written informed consent document. Translation will be provided as appropriate by institution.
• Inclusion of Women and Minorities: Both men and women and members of all ethnic groups are eligible for this trial.

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• Patients with radiographic tumors of, or involving, nonresectable midline, the basal ganglia, or brain stem as assessed by MRI.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to aminolevulinic acid (ALA). Patients should refrain from use of other potential phototoxic substances (e.g. tetracyclines, sulfonamides, fluoroquinolones, hypericin extracts) for 72 h.
• Personal or family history of porphyria.
• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. . Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with 5-aminolevulinic acid (5-ALA), breastfeeding should be discontinued if the mother is treated with 5-aminolevulinic acid (5-ALA).
• Women who are pregnant will be excluded from the trial as aminolevulinic acid (ALA) is unknown to be teratogenic or have abortifacient effects Prior history of GI perforation, diverticulitis, and/or peptic ulcer disease.

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Physician

Hugh Moulding, MD

Study Coordinator

Megan Gavinski, BS

484-503-4157

Megan.gavinski@sluhn.org

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Treatment Agent: Temozolomide, radiotherapy, PCV chemotherapy

Synopsis: The purpose of this study is to see if you have a certain kind of tumor, one that is missing part of both chromosomes 1 and 19. These missing parts of chromosomes are called a “tumor marker” as they make the tumor distinct from other kinds of tumors. This tumor marker is called the 1p/19q co-deletion. Tumors with this 1p/19q co-deletion typically have a more favorable outcome than other types of anaplastic glioma. Standard therapy at this point in time is surgery followed by radiation therapy.

Another purpose of this study is to see if patients survive for a longer period of time without the tumor progressing if thy are treated with a combination of radiotherapy with temozolomide chemotherapy as compared to radiotherapy with PCV chemotherapy (procarbazine, CCNU, and vincristine, which are the drugs that are used in this chemotherapy treatment, also known as PCV)

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• Age ≥ 18 years
• Newly diagnosed and ≤ 3 months from surgical diagnosis
• Histological confirmation of anaplastic glioma (oligodendroglioma, mixed, or astrocytoma [WHO grade III], as determined by pre-registration central pathology review. Note: Mixed gliomas are eligible, regardless of the degree of astrocytic or oligodendrocytic predominance, as long as the tumor is also co-deleted for 1p and 19q.
• Tumor is co-deleted for 1p and 19q.
• Surgery (partial or gross total resection or biopsy) must be performed ≥ 2 weeks prior to registration. Patient must have recovered from the effects of surgery.
• The following laboratory values obtained ≤ 21 days prior to registration.
  • Absolute neutrophil count (ANC) ≥ 1500/mm^3
  • Platelet (PLTs) count ≥ 100,000/mm^3
  • Hemoglobin (Hgb) > 9.0g/dL
  • Total bilirubin ≤ 1.5 x upper limit of normal (ULN)
  • Serum glutamic oxaloacetic transaminase (SGOT) aspartate transaminase (AST) ≤ 3 x ULN
  • Creatinine ≤ 1.5 x ULN
• Negative serum or urine pregnancy test done ≤ 7 days prior to registration for women of childbearing potential only.
• Willing and able to complete neurocognitive testing without assistance and the Quality of Life (QOL) questionnaires with or without assistance
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
• Provide informed written consent.
• Willing to return to enrolling institution for follow-up during the Active Monitoring Phase (ie, active treatment and observation portion of the study)
• Mandatory Tissue Samples for Correlative Research - Patient is willing to provide tissue samples for correlative research purposes

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• Pregnant women, nursing women, men or women of childbearing potential who are unwilling to employ adequate contraception during this study and for up to 6 months following the completion of temozolomide treatments.
• Received any prior surgery, radiation therapy or chemotherapy for any central nervous system (CNS) neoplasm. Note: Patients who have had a prior low grade glioma with or without surgery and who now have anaplastic glioma with no prior radiation or chemotherapy are eligible for the study.
• Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens.
• Concomitant serious immunocompromised status (other than that related to concomitant steroids).
• Patients known to be Human Immunodeficiency Virus (HIV) positive and currently receiving retroviral therapy. Note: Patients known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for the study.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm.
• Other active malignancy within 5 years of registration. Exceptions:
  • Non-melanotic skin cancer or carcinoma in situ of the cervix. Note: if there is a history of prior malignancy, the patient must not be receiving other specific treatment (other than hormonal therapy) for their cancer.
• History of myocardial infarction ≤ 6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias.
• Recent history of hepatitis infection or treating physician determined that the patient would be at significant risk of reactivation of hepatitis.

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Physician

Nimisha Deb, MD

Study Coordinator

Megan Gavinski, BS

484-503-4157

Megan.gavinski@sluhn.org

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Treatment: Radiation 

Synopsis: This randomized phase III trial studies how well radiation therapy works compared with observation in treating patients with newly diagnosed grade II meningioma that has been completely removed by surgery. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors..

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• PRIOR TO STEP 1 REGISTRATION:
• The patient must have a newly diagnosed unifocal intracranial meningioma, gross totally resected, and histologically confirmed as WHO grade II based upon pathology findings at the enrolling institution; WHO grade will be assigned according to WHO 2016 criteria
• Gross total resection (GTR) will be interpreted as modified Simpson grade 1-3 without gross residual dural-based or extradural tumor; GTR must be confirmed both by modified Simpson grade and by post-operative magnetic resonance imaging (MRI) findings
• Step 1 registration must occur within 180 days of the initial surgery; within this 180 day interval, a second surgery is permitted in order to achieve GTR, but even with a second surgery, step 1 registration must occur within 180 days of the initial resection
• For step 1 registration the operating neurosurgeon must provide the modified Simpson grade
• GTR must be confirmed on post-operative imaging following the most recent surgery; submission of both pre-operative and post-operative MRIs is required for patients; if a second surgery is performed, submission of post-operative MRI is required and pre-operative MRI is required only if obtained; all sequences obtained in the pre- and post-operative MR imaging are to be submitted to National Radiology Group (NRG) Oncology for study registration; imaging subsequent to enrollment must include pre and post gadolinium contrast-enhanced three-dimensional spoiled gradient (SPGR), magnetization-prepared rapid gradient echo (MP-RAGE), or turbo field echo (TFE) MRI scan and an axial T2 fluid attenuated inversion recovery (FLAIR) sequence; to yield acceptable image quality, the gadolinium contrast-enhanced three-dimensional SPGR, MP-RAGE, or TFE axial MRI scan should use the smallest possible axial slice thickness not exceeding 1.5 mm; the post-operative MRI must be completed within sufficient time to permit step 1 registration within 180 days of the initial resection; these same conditions apply in the setting of a second surgical procedure, although if a second surgery is completed, step 1 registration must still occur with 180 days of initial surgery; computed tomography (CT) imaging is not required, but may be obtained if desired clinically, for instance to assess calcifications or hyperostosis
• The patient or a legally authorized representative must provide study-specific informed consent prior to study entry
• If the patient is a primary English speaker, the patient must participate in the NCF and patient reported outcomes part of the study; if the patient is a primary French or Spanish speaker, the patient must participate in the patient reported outcomes part of the study
• NOTE: Central pathology review must occur between steps 1 and 2 of registration; once appropriate pathology specimens are received, central pathology review will occur within 15 days, and must confirm WHO grade II meningioma before the patient can proceed to step 2 registration and randomization
• PRIOR TO STEP 2 REGISTRATION:
• Histologically confirmed diagnosis of WHO grade II meningioma confirmed by central pathology review prior to step 2 registration
• History/physical examination, including neurologic examination within 60 days prior to step 2 registration
• Post-operative Zubrod performance status 0-1 within 60 days prior to step 2 registration
• If the patient is a woman is of childbearing potential, a serum pregnancy test, obtained within 14 days prior to step 2 registration, must be negative, and, if randomized to receive radiation therapy, the woman must agree to use contraception

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• Optic nerve sheath meningioma, spinal or other extracranial meningioma, multiple meningiomas, hemangiopericytoma
• Definitive evidence of metastatic meningioma
• Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years (carcinoma in situ of the breast, oral cavity, cervix, melanoma in situ, or other non-invasive malignancies are permissible)
• Previous radiotherapy to the scalp, cranium, brain, or skull base and radiation-induced meningiomas
• Major medical illnesses or psychiatric impairments, which in the investigators opinion, will prevent administration or completion of the protocol therapy and/or preclude informed consent; these include, but are not restricted to:
  • Unstable angina and/or congestive heart failure requiring hospitalization at the time of step 2 registration
  • Transmural myocardial infarction within the last 6 months prior to step 2 registration
  • Acute bacterial or fungal infection requiring intravenous antibiotics at the time of step 2 registration
  • Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of step 2 registration
  • Type II neurofibromatosis (NF2)
  • Ailments entailing substantial increases in sensitivity and side effect risk from radiation therapy (ataxia telangiectasia, Nijmegen breakage syndrome, and human immunodeficiency virus (HIV) with CD4 count < 200 cells/microliter); HIV testing is not required for eligibility for this protocol, and known HIV positive patients are eligible, provided they are under treatment with highly active antiretroviral therapy (HAART) and have a CD4 count >= 200 cells/microliter within 30 days prior to step 2 registration
  • Inability to undergo MRI with and without contrast (e.g. claustrophobia, non-MRI compatible implant or foreign body, etc) or receive gadolinium; note that patients with severe claustrophobia are permitted on this study if they are willing and able to undergo MRI with adequate sedation or anesthesia
• Pregnancy and/or nursing females

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