Clinical Trial Finder

Inclusion Criteria:

1. Has been treated previously with bevacizumab and (or) temozolomide. 2. Be willing and able to provide written informed consent/assent for the trial. 3. Be >/= 18 years of age on day of signing informed consent. 4. Have histologically confirmed World Health Organization Grade IV malignant glioma (glioblastoma or gliosarcoma). Participants will be eligible if the original histology was low-grade glioma and a subsequent histological diagnosis of glioblastoma or variants is made. 5. Patients must be at first or second relapse and clinically require reoperation for tumor progression within 4 to 6 weeks. Note: Relapse is defined as progression following initial therapy (i.e., radiation, chemotherapy, or radiation+ chemotherapy). If the participant had a surgical resection for relapsed disease and no antitumor therapy instituted for up to 12 weeks, this is considered one relapse. For participants who had prior therapy for a low grade glioma, the surgical diagnosis of a high grade glioma will be considered first relapse. 6. Have measurable disease consisting of a minimal volume of 1 cm3. 7. Have provided tissue from an archival tissue sample of a tumor lesion. 8. Have a performance status of >/= 60 on the KPS. 9. Stable dose of steroids for 5 days, no more than 2 mg dexamethasone (or equivalent) total per day. 10. Demonstrate adequate organ function as defined in Table 1, all screening labs should be performed within 14 days prior to registration. 1) Hematological : Absolute neutrophil count (ANC) >/=1,500 /mcL; Platelets >/=100,000 / mcL; Hemoglobin >/= 9 g/dL or >/= 5.6 mmol/L. 2) Renal: Serum creatinine /= 60 mL/min for subject with creatinine levels > 1.5 X institutional ULN. 11. Hepatic: Serum total bilirubin 1.5 ULN; AST (SGOT) and ALT (SGPT) 1 year. 14. Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 90 days after the last dose of study therapy.

Exclusion Criteria:

1. Has tumor localized primarily to the brainstem or spinal cord. 2. There are acute or chronic diseases of the maxillary and paranasal sinuses, sphenoid sinuses, the sinuses of the trellis, early or current traumatic injuries of these zones, fractures of the nasal septum, congenital malformations of the development of bone tissue of the latticed bone. 3. Is currently participating in or has participated in a study of an investigational agent or using an investigational device 4 weeks since last dose of agent administration. 4. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy > 2 mg of dexamethasone total per day or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. 5. Has had a prior monoclonal antibody within 4 weeks prior to study Day 1 or who has not recovered (i.e.,

- Note: Subjects with alopecia, 7. Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy. 8. Has known carcinomatous meningitis, extracranial disease, or multifocal disease. 9. Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. 10. Has evidence of interstitial lung disease or active, non-infectious pneumonitis. 11. Has an active infection requiring systemic therapy. 12. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator. 13. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. 14. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 90 days after the last dose of trial treatment. 15. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies). 16. Has known history of Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).

This is an open-label study, Phase 1 study evaluating the preliminary safety, efficacy, tolerability and clinical benefit of Nasal Spray NST-4G in patients with Recurrent Glioblastoma, Gliosarcoma,Anaplastic Gliomas. Acceptable subjects included in the study will receive Nasal Spray NST-4G, administered twice daily for 7 weeks intranasally. Every 8th day, a blood function (hematopoiesis) is examined . Patients may continue to receive subsequent nasal spray cycles if the subject is not intolerant of the test product, does not withdraw consent or the individual no longer receives clinical benefit (the factors taken for consideration will be the progression of the disease, expressed in increasing neuropathy, hemiparesis, pain intensification ,DLT events, Clinical signs of deteriorating quality of life (QOL). The evaluation of the tumor size will be repeated using the MRI method with a contrast agent after each 7-week nasal spray cycle. The use of nasal spray is a non-invasive method of treatment that does not require specialized conditions for therapy

Arms

Active Comparator: Axitinib

A single dose of Axitinib - 1 mg in a liquid form in the composition (Axitinib+Sunitinib+Pazopanib) of the nasal spray.

Active Comparator: Sunitinib

A single dose of Sunitinib- 5 mg in a liquid form in the composition (Axitinib+Sunitinib+Pazopanib) of the nasal spray.

Active Comparator: Pazopanib

A single dose of Pazopanib-5 mg in a liquid form in the composition (Axitinib+Sunitinib+Pazopanib) of the nasal spray.

Interventions

Drug: - Axitinib 1 MG

Pharmaceutical composition of Axitinib 5MG +Sunitinib 5MG + Pazopanib 5MG in the liquid form of a nasal spray NST-4-G. Subjects take a nasal spray BID at a single dose in each nostril (approximately at the same time of day) for 7 weeks or unacceptable toxicity or other adverse events.

Drug: - Sunitinib 5 MG

Pharmaceutical composition of Axitinib 5MG +Sunitinib 5MG + Pazopanib 5MG in the liquid form of a nasal spray NST-4-G.

Drug: - Pazopanib 5 MG

Pharmaceutical composition of Axitinib 5MG +Sunitinib 5MG + Pazopanib 5MG in the liquid form of a nasal spray NST-4-G.