Phase I Clinical Trial of Nasal Spray in Treating Patients With Recurrent Glioblastoma, Gliosarcoma, Glioma
Overview
- Phase
- Phase 1
- Intervention
- Axitinib 1 MG
- Conditions
- Recurrent Glioblastoma
- Sponsor
- Center Trials & Treatment
- Locations
- 2
- Primary Endpoint
- The definition of survival without progression of disease
- Status
- Withdrawn
- Last Updated
- 7 years ago
Overview
Brief Summary
This is a study to determine the efficacy, safety and clinical benefit (how well the drugs works), of the pharmaceutical compositions in Nasal Spray NST-4G for the treatment of brain tumors( Recurrent Glioblastoma, Gliosarcoma,Anaplastic Gliomas, Previously Treated).
All drugs target the inhibition of the growth factors and neo-angiogenesis as one the main reasons for the growth of the tumor.
The purpose of the Nasal Spray NST-4G study is to determine the safety and tolerability in order to establish the best dose level to be used in future studies.
Detailed Description
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
Investigators
Eligibility Criteria
Inclusion Criteria
- •Has been treated previously with bevacizumab and (or) temozolomide.
- •Be willing and able to provide written informed consent/assent for the trial.
- •Be \>/= 18 years of age on day of signing informed consent.
- •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.
- •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.
- •Have measurable disease consisting of a minimal volume of 1 cm
- •Have provided tissue from an archival tissue sample of a tumor lesion.
- •Have a performance status of \>/= 60 on the KPS.
- •Stable dose of steroids for 5 days, no more than 2 mg dexamethasone (or equivalent) total per day
- •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 \</= 1.5 X upper limit of normal (ULN) OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) \>/= 60 mL/min for subject with creatinine levels \> 1.5 X institutional ULN.
Exclusion Criteria
- •Has tumor localized primarily to the brainstem or spinal cord.
- •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.
- •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.
- •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.
- •Has had a prior monoclonal antibody within 4 weeks prior to study Day 1 or who has not recovered (i.e., \</= Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
- •Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., \</= Grade 1 or at baseline) from adverse events due to a previously administered agent. - Note: Subjects with alopecia, \</= Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
- •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.
- •Has known carcinomatous meningitis, extracranial disease, or multifocal disease.
- •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.
- •Has evidence of interstitial lung disease or active, non-infectious pneumonitis.
Arms & Interventions
Axitinib
A single dose of Axitinib - 1 mg in a liquid form in the composition (Axitinib+Sunitinib+Pazopanib) of the nasal spray.
Intervention: Axitinib 1 MG
Sunitinib
A single dose of Sunitinib- 5 mg in a liquid form in the composition (Axitinib+Sunitinib+Pazopanib) of the nasal spray.
Intervention: Sunitinib 5 MG
Pazopanib
A single dose of Pazopanib-5 mg in a liquid form in the composition (Axitinib+Sunitinib+Pazopanib) of the nasal spray.
Intervention: Pazopanib 5 MG
Outcomes
Primary Outcomes
The definition of survival without progression of disease
Time Frame: From the date of commencement of participation in the study until the date of first documented progression or date of death from any cause, whichever came first /assessed up to 48 months/
The definition of survival without progression of disease is estimated as time of the disease-free period / absence of continued tumor growth (in weeks) by objective methods of control (MRI or CT)
Secondary Outcomes
- The definition of overall survival(From the date of commencement of participation in the study until date of death from any cause / assessed up to 60 months/)
- The definition late toxicity to maximum tolerated dose (MTD)(From the date of commencement of participation in the study until the onset of adverse event /assessed up to 48 months/)