Recurrent GlioblastomaPhase 1NCT03275558
Clinical Trial of the Use of the Nasal Spray of Patients With Recurrence of Glioblastoma
A Phase 1 study testing Axitinib 1 MG, Sunitinib 5 MG and Pazopanib 5 MG in people with Recurrent Glioblastoma and Gliosarcoma, run by Center Trials & Treatment at 2 sites in 2 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Recurrent Glioblastoma, Gliosarcoma, Anaplastic Gliomas
- What is being tested?
- Axitinib 1 MG, Sunitinib 5 MG and Pazopanib 5 MG
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 17 Jul 2018to 17 Jul 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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 cm3.
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- 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.
- Hepatic: Serum total bilirubin </= 1.5 X ULN OR Direct bilirubin </= ULN for subjects with total bilirubin levels > 1.5 ULN; AST (SGOT) and ALT (SGPT) </= 2.5 X ULN, Coagulation: International Normalized Ratio (INR) or Prothrombin Time (PT) </= 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants; Activated Partial Thromboplastin Time (aPTT) </= 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants.
- Female subject of childbearing potential should have a negative serum pregnancy test.
- Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 90 days after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.
- 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.
Who cannot join
- 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.
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- 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.
- Has an active infection requiring systemic therapy.
- 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.
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- 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.
- Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
- Has known history of Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
About this study
Official title: Phase I Clinical Trial of Nasal Spray in Treating Patients With Recurrent Glioblastoma, Gliosarcoma, Glioma
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.
Read the 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
- Conditions
- Recurrent Glioblastoma, Gliosarcoma, Anaplastic Gliomas
- Being tested
- Axitinib 1 MG, Sunitinib 5 MG, Pazopanib 5 MG
- Keywords
- Nasal Spray, Gliosarcoma, Glioblastoma, Gliomas
- Medical subject headings
- Glioblastoma, Gliosarcoma, Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Axitinib 1 MGDrug
Also called AG 013736, Inlyta
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.
Sunitinib 5 MGDrug
Also called SU11248, Sutent
Pharmaceutical composition of Axitinib 5MG +Sunitinib 5MG + Pazopanib 5MG in the liquid form of a nasal spray NST-4-G.
Pazopanib 5 MGDrug
Also called GW786034, Votrient
Pharmaceutical composition of Axitinib 5MG +Sunitinib 5MG + Pazopanib 5MG in the liquid form of a nasal spray NST-4-G.
| Study group | Role | What they receive |
|---|---|---|
| Axitinib | Active comparator | A single dose of Axitinib - 1 mg in a liquid form in the composition (Axitinib+Sunitinib+Pazopanib) of the nasal spray. Receives: Drug: Axitinib 1 MG |
| Sunitinib | Active comparator | A single dose of Sunitinib- 5 mg in a liquid form in the composition (Axitinib+Sunitinib+Pazopanib) of the nasal spray. Receives: Drug: Sunitinib 5 MG |
| Pazopanib | Active comparator | A single dose of Pazopanib-5 mg in a liquid form in the composition (Axitinib+Sunitinib+Pazopanib) of the nasal spray. Receives: Drug: Pazopanib 5 MG |
What is being measured
The primary outcome is the main question the study is designed to answer.
The definition of survival without progression of disease
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)
Measured: 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/
Secondary outcomes (2)
The definition of overall survival
The determine overall survival from the date of commencement of participation in the study until date of death from any cause.
Measured: 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)
To determine late toxicity for the maximum tolerated dose is estimated a function of hematopoiesis of patients by blood sampling every 8th day The MTD is based upon dose-limiting toxicities (DLTs) experienced during Cycle 1 of treatment. The MTD is the dose level at which 0/6 or 1/6 patients experience DLT with at least two patients experiencing DLT at the next higher dose level. Using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, DLTs are defined as: Grade 4 neutropenia lasting greater than 5 days; Grade 3 thrombocytopenia; the occurrence of non-hematologic Grade 3 or greater drug-related adverse events excluding Grade ≥ 3 elevation in alkaline phosphatase, Grade ≥ 3 nausea or vomiting unless occurring despite the use of standard anti-emetics or Grade 3 diarrhea unless occurring despite standard anti-diarrheal therapy; > 14 day delay to re-treat due to failure to resolve drug-related toxicity to re-treatment criteria or pre-treatment baseline.
Measured: From the date of commencement of participation in the study until the onset of adverse event /assessed up to 48 months/
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Sep 2017
- Study start17 Jul 2018
- Primary completion17 Jul 2018
- Study completion17 Jul 2018
Why it stopped: Study halted prior to enrollment of first participant. (It has been determined on 2018 May 15 that the NCT03275558 study will be stopped by sponsor decision)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Recurrent GlioblastomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Center Trials & Treatment
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Ivo Reznic, PhD, Principal investigator, Center Trials & Treatment Inc.Oliever R Kolb, Study director, Center Trials & Treatment Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03275558
- Sponsor's protocol ID
- NST-4-G
- Status last verified
- Jul 2018
- First submitted
- 30 Aug 2017
- Last updated
- 19 Jul 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: IB, SAP. ICF E-mail: info@trials.clinic
Study at a glance
From the registry record, last updated by the sponsor on 19 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Clinical Trial of Nasal Spray in Treating Patients With Recurrent Glioblastoma, Gliosarcoma, Glioma
- ClinicalTrials.gov ID
- NCT03275558
- Acronym / sponsor ID
- NST-4-G
- Conditions
- Recurrent Glioblastoma, Gliosarcoma, Anaplastic Gliomas
- Keywords
- Nasal Spray, Gliosarcoma, Glioblastoma, Gliomas
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Study halted prior to enrollment of first participant. (It has been determined on 2018 May 15 that the NCT03275558 study will be stopped by sponsor decision)
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Center Trials & TreatmentUniversity, hospital or other
- Study start
- 17 Jul 2018 (actual)
- Primary completion
- 17 Jul 2018 (actual)
- Study completion
- 17 Jul 2018 (actual)
- First posted
- 7 Sep 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Axitinib | Active comparator | Drug: Axitinib 1 MGA single dose of Axitinib - 1 mg in a liquid form in the composition (Axitinib+Sunitinib+Pazopanib) of the nasal spray. |
| Sunitinib | Active comparator | Drug: Sunitinib 5 MGA single dose of Sunitinib- 5 mg in a liquid form in the composition (Axitinib+Sunitinib+Pazopanib) of the nasal spray. |
| Pazopanib | Active comparator | Drug: Pazopanib 5 MGA single dose of Pazopanib-5 mg in a liquid form in the composition (Axitinib+Sunitinib+Pazopanib) of the nasal spray. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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.
Key exclusion criteria (16 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Axitinib 1 MGAlso: AG 013736, InlytaPharmaceutical 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 | Axitinib |
| Sunitinib 5 MGAlso: SU11248, SutentPharmaceutical composition of Axitinib 5MG +Sunitinib 5MG + Pazopanib 5MG in the liquid form of a nasal spray NST-4-G. | Drug | Sunitinib |
| Pazopanib 5 MGAlso: GW786034, VotrientPharmaceutical composition of Axitinib 5MG +Sunitinib 5MG + Pazopanib 5MG in the liquid form of a nasal spray NST-4-G. | Drug | Pazopanib |
Primary outcome
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)
2 secondary outcomes
The definition of overall survival
Time frame: 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)
Time frame: From the date of commencement of participation in the study until the onset of adverse event /assessed up to 48 months/
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Jul 2018.
- Individual participant dataSharing planned: Yes. IB, SAP. ICF E-mail: info@trials.clinic
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ivo Reznic, PhD principal investigator
Center Trials & Treatment Inc.
Oliever R Kolb study director
Center Trials & Treatment Inc.
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Axitinib 1 MG, Sunitinib 5 MG and Pazopanib 5 MG in people with Recurrent Glioblastoma and Gliosarcoma, run by Center Trials & Treatment at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 19 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Hong Kong, Singapore. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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/). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Jul 2018.