GlioblastomaPhase 1NCT02133183
Sapanisertib Before and After Surgery in Treating Patients With Recurrent Glioblastoma
A Phase 1 study testing Laboratory Biomarker Analysis, Pharmacological Study and Sapanisertib in people with Glioblastoma and Gliosarcoma, run by National Cancer Institute (NCI) at 10 sites in United States.
Trial summary
This partially randomized pilot phase I trial studies how much sapanisertib reaches the brain tumor and how well it works when given before and after surgery in treating patients with glioblastoma that has grown or come back and requires surgery. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma, Gliosarcoma
- What is being tested?
- Laboratory Biomarker Analysis, Pharmacological Study and Sapanisertib
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 10 sitesUnited States
- Study dates
- 2 Jul 2014to 31 Oct 2023
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must have histologically proven glioblastoma or gliosarcoma which is progressive or recurrent following radiation therapy +/- chemotherapy
- Patients must have measurable, supratentorial contrast-enhancing progressive or recurrent glioblastoma or gliosarcoma by magnetic resonance imaging (MRI) imaging within 21 days of starting treatment; patient must be able to tolerate MRIs
- Patients may have had treatment for no more than 2 prior relapses
- Patients must have recovered from severe toxicity of prior therapy; the following intervals from previous treatments are required to be eligible:
- 12 weeks from the completion of radiation
- 6 weeks from a nitrosourea chemotherapy or mitomycin C
Show all 31Show fewer
- 3 weeks from a non-nitrosourea chemotherapy
- 4 weeks from any investigational (not Food and Drug Administration [FDA]-approved) agents
- 2 weeks from administration of a non-cytotoxic, FDA-approved agent except bevacizumab/vascular endothelial growth factor receptor (VEGFR) inhibitors (e.g., erlotinib, hydroxychloroquine, etc.)
- 6 weeks from bevacizumab/VEGFR inhibitors
- Patients must be undergoing surgery that is clinically indicated as determined by their care providers
- Patients must be eligible for surgical resection according to the following criteria:
- Part 1 Patients: Expectation that the surgeon is able to resect at least 350 mg of tumor from enhancing tumor and at least 350 mg from non-enhancing tumor with low risk of inducing neurological injury
- Part 2 Patients: Expectation that the surgeon is able to resect at least 1000 mg from enhancing tumor and at least 350 mg from non-enhancing tumor with low risk of inducing neurological injury
- Patients must have a Karnofsky performance status >= 60% (i.e. the patient must be able to care for himself/herself with occasional help from others)
- Absolute neutrophil count >= 1,500/mcL
- Platelets >= 100,000/mcL
- Hemoglobin >= 9 g/dL
- Total bilirubin =< 1.5 x upper limit of normal (ULN)
- Fasting serum glucose =< 130 MG/DL
- HbA1c =< 7.0%
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 × institutional upper limit of normal
- Creatinine =< institutional upper limit of normal OR
- Creatinine clearance >= 50 ml/min/1.73 m^2 for patients with creatinine levels above institutional normal
- Activated partial thromboplastin time (APTT)/partial thromboplastin time (PTT) =< 1.5 x institutional upper limit of normal
- Patients must be able to provide written informed consent
- Women of childbearing potential must have a negative serum pregnancy test prior to study entry; women of childbearing potential and men must agree to practice 1 highly effective method of contraception and 1 additional effective (barrier) method, at the same time, prior to study entry, for the duration of study participation, and through 90 days (or longer, as mandated by local labeling [e.g. USPI, SmPC, etc.]) after the last dose of study drug; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately; men treated or enrolled on this protocol must also agree to use highly effective barrier contraception prior to the study, for the duration of study participation, and through 120 days after the last dose of study drug
- Patients must have no concurrent malignancy except curatively treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix, breast, or bladder; patients with prior malignancies must be disease-free for >= five years
- Patients must be able to swallow whole capsules
- Patients enrolled in Part 2 must have at least 20 (preferably 40) slides of archival tumor tissue from a prior surgery demonstrating GBM; patients enrolled in Part 1 will not be required to have archival tissue
- Patients with controlled diabetes are allowed on study; controlled diabetes is defined as < 130 ml/dL for the sake of this study
Who cannot join
- Patients receiving any other investigational agents are ineligible
- Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to MLN0128 (TAK-228) are ineligible
- Patients may not have had prior treatment with mTOR, peptidase inhibitor 3, skin-derived (PI3) kinase or Akt inhibitors
- Patients on enzyme-inducing anti-epileptic drugs (EIAED) are not eligible for treatment on this protocol; patients may be on non-enzyme inducing anti-epileptic drugs or not be taking any anti-epileptic drugs; patients previously treated with EIAED may be enrolled if they have been off the EIAED for 10 days or more prior to the first dose of MLN0128 (TAK-228)
- Patients must not have evidence of significant hematologic, renal, or hepatic dysfunction
- Patients must not have evidence of significant intracranial hemorrhage
Show all 23Show fewer
- Patients with a history of any of the following within the last 6 months prior to study entry are ineligible:
- Ischemic myocardial event, including angina requiring therapy and artery revascularization procedures
- Ischemic cerebrovascular event, including transient ischemic attack (TIA) and artery revascularization procedures
- Requirement for inotropic support (excluding digoxin) or serious (uncontrolled) cardiac arrhythmia (including atrial flutter/fibrillation, ventricular fibrillation or ventricular tachycardia)
- Placement of a pacemaker for control of rhythm
- New York Heart Association (NYHA) class III or IV heart failure
- Pulmonary embolism
- Patients with known significant active cardiovascular or pulmonary disease at the time of study entry are ineligible
- Patients with baseline prolongation of the rate-corrected QT interval (QTc) (e.g., repeated demonstration of QTc interval > 480 milliseconds, or history of congenital long QT syndrome, or torsades de pointes) are ineligible
- Patients with known diabetes mellitus which is poorly controlled (defined as hemoglobin A1c [HbA1c] > 7%) are ineligible; subjects with a history of transient glucose intolerance due to corticosteroid administration are allowed in this study if all other inclusion/exclusion have been met
- Patients who have initiated treatment with bisphosphonates less than 30 days prior to the first administration of MLN0128 (TAK-228) are ineligible; concurrent bisphosphonate use is only allowed if the bisphosphonate was initiated at least 30 days prior to the first administration of MLN0128 (TAK-228)
- For weekly MLN0128 (TAK-228) dose cohorts, patients taking proton pump inhibitors (PPIs) are ineligible unless these patients are able to switch to a histamine (H2) blocker and/or antacid
- Patients with known manifestations of malabsorption due to prior gastrointestinal (GI) surgery, GI disease, or for an unknown reason that may alter the absorption of MLN0128 (TAK-228) are ineligible
- Patients with 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, are ineligible
- Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with this agent
- Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible
- Subjects taking strong CYP3A4 and CYP2C19 inhibitors and/or inducers should be considered with caution; alternative treatments that are less likely to affect MLN0128 (TAK-228) metabolism, if available, should be considered; if a subject requires treatment with 1 or more of the strong CYP3A4 and CYP2C19 inhibitors and/or inducers, the study doctor should be consulted
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
United States10 sites
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, 35233
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Case Western Reserve University
Cleveland, Ohio, 44106
Cleveland Clinic Foundation
Cleveland, Ohio, 44195
Henry Ford Hospital
Detroit, Michigan, 48202
UCLA / Jonsson Comprehensive Cancer Center
Los Angeles, California, 90095
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, 15232
UCSF Medical Center-Parnassus
San Francisco, California, 94143
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157
About this study
Official title: Pilot Study of MLN0128 (TAK-228) in Preoperative Recurrent Glioblastoma (GBM) Patients
This partially randomized pilot phase I trial studies how much sapanisertib reaches the brain tumor and how well it works when given before and after surgery in treating patients with glioblastoma that has grown or come back and requires surgery. Sapanisertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Read the detailed description
PRIMARY OBJECTIVES:
- To evaluate the penetration of sapanisertib (MLN0128 [TAK-228]) across the blood brain barrier and achieve a concentration of 70 nM in tissue resected from a contrast enhancing region of the tumor in 60% of recurrent glioblastoma (GBM) patients. (Part I) II. To determine the ability of MLN0128 (TAK-228) to inhibit TOR complex (TORC)1/2 in the enhancing components of the tumor as determined by modulation of RPS6 phosphorylated Ser-235 (pS235) in reverse phase protein array (RPPA) assays. (Part II)
SECONDARY OBJECTIVES:
- To evaluate the penetration of MLN0128 (TAK-228) across the blood brain barrier by determining its concentration in tissue resected from a non-contrast enhancing region of the tumor. (Part I) II. To assess the plasma pharmacokinetics of MLN0128 (TAK-228) in patients with recurrent GBM. (Part I) III. To determine the ability of MLN0128 (TAK-228) to inhibit TORC1/2 in the non-enhancing components of the tumor as determined by modulation of RPS6 pS235 in RPPA assays. (Part II) IV. To assess the ability of MLN0128 (TAK-228) to inhibit TORC1/2 by evaluating pharmacodynamics (PD) markers by immunohistochemistry such as pS235, pS236, phosphorylated 4E-binding protein (p4EBP), phosphorylated-mechanistic target of rapamycin (serine/threonine kinase) (pmTOR), and AKTpSer473. (Phase II) V. To evaluate the safety profile of MLN0128 (TAK-228) in pre-operative patients with recurrent GBM.
VI. To estimate response rate, progression-free survival, and overall survival.
TERTIARY OBJECTIVES:
- To perform mass spectrometry imaging (MSI) to qualitatively assess the ability of MLN0128 (TAK-228) to penetrate the blood brain barrier and enter tumor tissue in enhancing and non-enhancing regions of the tumor. (Part I) II. To determine ex-vivo sensitivity of tumor neurosphere cultures (patient derived cell lines [PDCL]) established from surgical specimens to MLN0128 (TAK-228). (Part II) III. To explore the potential association of tumor genotype with progression-free survival among patients treated with MLN0128 (TAK-228). (Part II) IV. To determine the ability of MLN0128 (TAK-228) to inhibit TORC1/2 as determined by modulation of additional TORC1/2 markers in RPPA assays. (Part II)
OUTLINE:
PART I:
COHORT A: Patients receive sapanisertib orally (PO) once daily (QD) for 7-9 days (including 2-4 hours before surgery). On day 0, patients undergo surgery. Within 45 days after surgery, patients receive sapanisertib PO QD. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. If patients do not demonstrate adequate sapanisertib tumor tissue concentrations, patients are enrolled in Cohort B.
COHORT B: Patients receive sapanisertib PO 2-4 hours before surgery on day 0. Within 45 days after surgery, patients receive sapanisertib PO once weekly. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
PART II: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive sapanisertib PO according to the results from Part I. Patients also undergo surgery on day 0. Within 30 days after surgery, patients receive sapanisertib PO according to the results from Part I. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
ARM II: Patients undergo surgery on day 0. Within 30 days after surgery, patients receive sapanisertib PO according to the results from Part I. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days, every 2 months for 2 years, and then every 6 months thereafter.
- Conditions
- Glioblastoma, Gliosarcoma
- Being tested
- Laboratory Biomarker Analysis, Pharmacological Study, Sapanisertib, Therapeutic Conventional Surgery
- Medical subject headings
- Glioblastoma, Gliosarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Laboratory Biomarker AnalysisOther
Correlative studies
Correlative studies
SapanisertibDrug
Also called INK-128, INK128, MLN-0128, MLN0128
Given PO
Therapeutic Conventional SurgeryProcedure or surgery
Undergo surgery
| Study group | Role | What they receive |
|---|---|---|
| Arm I (sapanisertib before and after surgery) | Experimental | Patients receive sapanisertib PO according to the results from Part I. Patients also undergo surgery on day 0. Within 45 days after surgery, patients receive sapanisertib PO according to the results from Part I. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Receives: Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Drug: Sapanisertib; Procedure: Therapeutic Conventional Surgery |
| Arm II (sapanisertib after surgery) | Experimental | Patients undergo surgery on day 0. Within 45 days after surgery, patients receive sapanisertib PO according to the results from Part I. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Receives: Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Drug: Sapanisertib; Procedure: Therapeutic Conventional Surgery |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of patients who achieve a drug concentration >= 70 nM in contrast enhancing tumor tissue
The proportion of patients who achieve a drug concentration >= 70 nM in contrast enhancing tumor tissue will be calculated and the 90% confidence interval will be estimated using binomial distribution.
Measured: Up to 2 years
Difference in ratio of the S6 phosphorylation over the total between the two groups
Two sample t-test will be used for the hypothesis testing of a difference in ratio of the S6 phosphorylation over the total between the two groups.
Measured: Up to 2 years
Difference of the pS6 concentration between the two groups
Two sample t-test will be used for the hypothesis testing of a difference in ratio of the S6 phosphorylation over the total between the two groups. A "heat map" or "heat map visualization" may also be used to present and examine possible difference in clustering signaling pathway activation between the groups.
Measured: Up to 2 years
Secondary outcomes (8)
Sapanisertib concentration in non-enhancing tumor
Will be summarized using descriptive statistics or two-group comparison between groups. The Spearman correlation coefficient might be used to assess potential correlations between pathway modulation scores and tumor growth measured by KI67 (proliferation) and cleaved caspase 3 (apoptosis/cell death).
Measured: Up to 2 years
Sapanisertib concentration in blood
Will be summarized using descriptive statistics or two-group comparison between Groups A and B. The Spearman correlation coefficient might be used to assess potential correlations between pathway modulation scores and tumor growth measured by KI67 (proliferation) and cleaved caspase 3 (apoptosis/cell death).
Measured: Up to 2 years
Inhibition TORC1/2 in the non-enhancing components of the tumor as determined by modulation of RPS6 pS235 in reverse phase protein array (RPPA) assays
Will be summarized using descriptive statistics or two-group comparison between Groups A and B. The Spearman correlation coefficient might be used to assess potential correlations between pathway modulation scores and tumor growth measured by KI67 (proliferation) and cleaved caspase 3 (apoptosis/cell death).
Measured: Up to 2 years
Pharmacodynamic marker such as pS6 (by immunohistochemistry), p4EBP, pmTOR, and AKTpSer473 compared to the control
Will be summarized using descriptive statistics or two-group comparison between Groups A and B. The Spearman correlation coefficient might be used to assess potential correlations between pathway modulation scores and tumor growth measured by KI67 (proliferation) and cleaved caspase 3 (apoptosis/cell death).
Measured: Up to 2 years
Incidence of toxicity graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0
All treatment or surgically related adverse events will be reported descriptively. A proportion of toxicity grade >= 3 will be estimated using binomial distribution.
Measured: Up to 30 days
Tumor response
The proportion of patients who had tumor response (partial response + complete response) during the course of treatment will be estimated using the exact binomial distribution.
Measured: Up to 2 years
Progression-free survival (PFS)
PFS along with 95% confidence interval will be estimated using Kaplan-Meier method.
Measured: Time from date of post-surgical treatment start to the date progressive disease was defined, assessed up to 2 years
Overall survival (death)
Overall survival along with 95% confidence interval will be estimated using Kaplan-Meier method.
Measured: Time from the date of post-surgical treatment start to the date death occurred, assessed up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 May 2014 (estimated)
- Study start2 Jul 2014
- Primary completion31 Jan 2020
- Study completion31 Oct 2023
Why it stopped: Other - Lapse in funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for GlioblastomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Eudocia Q Lee, Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02133183
- Sponsor's protocol ID
- NCI-2014-00907
- Other IDs
- NCI-2014-00907, ABTC-1301, 1301, ABTC-1301, ABTC-1301, U01CA137443, UM1CA137443
- Status last verified
- Apr 2024
- First submitted
- 6 May 2014
- Last updated
- 4 Apr 2024
- Results posted
- No
- Data monitoring committee
- No
Publications
Arnold A, Rodriguez F, Eberhart CG, Raabe EH. Response to letter to the editor: "All models are wrong; some models are useful". Neuro Oncol. 2020 Sep 29;22(9):1406-1407. doi: 10.1093/neuonc/noaa137. No abstract available.
PubMed 32597469
Study at a glance
From the registry record, last updated by the sponsor on 4 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study of MLN0128 (TAK-228) in Preoperative Recurrent Glioblastoma (GBM) Patients
- ClinicalTrials.gov ID
- NCT02133183
- Acronym / sponsor ID
- NCI-2014-00907
- Conditions
- Glioblastoma, Gliosarcoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Other - Lapse in funding
- Enrolment
- 40 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 2 Jul 2014 (actual)
- Primary completion
- 31 Jan 2020 (actual)
- Study completion
- 31 Oct 2023 (actual)
- First posted
- 7 May 2014 (estimated)
- 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 partially randomized pilot phase I trial studies how much sapanisertib reaches the brain tumor and how well it works when given before and after surgery in treating patients with glioblastoma that has grown or come back and requires surgery. Sapanisertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Detailed description
PRIMARY OBJECTIVES:
- To evaluate the penetration of sapanisertib (MLN0128 [TAK-228]) across the blood brain barrier and achieve a concentration of 70 nM in tissue resected from a contrast enhancing region of the tumor in 60% of recurrent glioblastoma (GBM) patients. (Part I) II. To determine the ability of MLN0128 (TAK-228) to inhibit TOR complex (TORC)1/2 in the enhancing components of the tumor as determined by modulation of RPS6 phosphorylated Ser-235 (pS235) in reverse phase protein array (RPPA) assays. (Part II)
SECONDARY OBJECTIVES:
- To evaluate the penetration of MLN0128 (TAK-228) across the blood brain barrier by determining its concentration in tissue resected from a non-contrast enhancing region of the tumor. (Part I) II. To assess the plasma pharmacokinetics of MLN0128 (TAK-228) in patients with recurrent GBM. (Part I) III. To determine the ability of MLN0128 (TAK-228) to inhibit TORC1/2 in the non-enhancing components of the tumor as determined by modulation of RPS6 pS235 in RPPA assays. (Part II) IV. To assess the ability of MLN0128 (TAK-228) to inhibit TORC1/2 by evaluating pharmacodynamics (PD) markers by immunohistochemistry such as pS235, pS236, phosphorylated 4E-binding protein (p4EBP), phosphorylated-mechanistic target of rapamycin (serine/threonine kinase) (pmTOR), and AKTpSer473. (Phase II) V. To evaluate the safety profile of MLN0128 (TAK-228) in pre-operative patients with recurrent GBM.
VI. To estimate response rate, progression-free survival, and overall survival.
TERTIARY OBJECTIVES:
- To perform mass spectrometry imaging (MSI) to qualitatively assess the ability of MLN0128 (TAK-228) to penetrate the blood brain barrier and enter tumor tissue in enhancing and non-enhancing regions of the tumor. (Part I) II. To determine ex-vivo sensitivity of tumor neurosphere cultures (patient derived cell lines [PDCL]) established from surgical specimens to MLN0128 (TAK-228). (Part II) III. To explore the potential association of tumor genotype with progression-free survival among patients treated with MLN0128 (TAK-228). (Part II) IV. To determine the ability of MLN0128 (TAK-228) to inhibit TORC1/2 as determined by modulation of additional TORC1/2 markers in RPPA assays. (Part II)
OUTLINE:
PART I:
COHORT A: Patients receive sapanisertib orally (PO) once daily (QD) for 7-9 days (including 2-4 hours before surgery). On day 0, patients undergo surgery. Within 45 days after surgery, patients receive sapanisertib PO QD. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. If patients do not demonstrate adequate sapanisertib tumor tissue concentrations, patients are enrolled in Cohort B.
COHORT B: Patients receive sapanisertib PO 2-4 hours before surgery on day 0. Within 45 days after surgery, patients receive sapanisertib PO once weekly. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
PART II: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive sapanisertib PO according to the results from Part I. Patients also undergo surgery on day 0. Within 30 days after surgery, patients receive sapanisertib PO according to the results from Part I. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
ARM II: Patients undergo surgery on day 0. Within 30 days after surgery, patients receive sapanisertib PO according to the results from Part I. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days, every 2 months for 2 years, and then every 6 months thereafter.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I (sapanisertib before and after surgery) | Experimental | Other: Laboratory Biomarker Analysis, Other: Pharmacological Study, Drug: Sapanisertib, Procedure: Therapeutic Conventional SurgeryPatients receive sapanisertib PO according to the results from Part I. Patients also undergo surgery on day 0. Within 45 days after surgery, patients receive sapanisertib PO according to the results from Part I. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
| Arm II (sapanisertib after surgery) | Experimental | Other: Laboratory Biomarker Analysis, Other: Pharmacological Study, Drug: Sapanisertib, Procedure: Therapeutic Conventional SurgeryPatients undergo surgery on day 0. Within 45 days after surgery, patients receive sapanisertib PO according to the results from Part I. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (31 listed)
- Patients must have histologically proven glioblastoma or gliosarcoma which is progressive or recurrent following radiation therapy +/- chemotherapy
- Patients must have measurable, supratentorial contrast-enhancing progressive or recurrent glioblastoma or gliosarcoma by magnetic resonance imaging (MRI) imaging within 21 days of starting treatment; patient must be able to tolerate MRIs
- Patients may have had treatment for no more than 2 prior relapses
- Patients must have recovered from severe toxicity of prior therapy; the following intervals from previous treatments are required to be eligible:
- Patients must be undergoing surgery that is clinically indicated as determined by their care providers
Key exclusion criteria (23 listed)
- Patients receiving any other investigational agents are ineligible
- Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to MLN0128 (TAK-228) are ineligible
- Patients may not have had prior treatment with mTOR, peptidase inhibitor 3, skin-derived (PI3) kinase or Akt inhibitors
- Patients on enzyme-inducing anti-epileptic drugs (EIAED) are not eligible for treatment on this protocol; patients may be on non-enzyme inducing anti-epileptic drugs or not be taking any anti-epileptic drugs; patients previously treated with EIAED may be enrolled if they have been off the EIAED for 10 days or more prior to the first dose of MLN0128 (TAK-228)
- Patients must not have evidence of significant hematologic, renal, or hepatic dysfunction
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 |
|---|---|---|
| Laboratory Biomarker AnalysisCorrelative studies | Other | Arm I (sapanisertib before and after surgery), Arm II (sapanisertib after surgery) |
| Pharmacological StudyCorrelative studies | Other | Arm I (sapanisertib before and after surgery), Arm II (sapanisertib after surgery) |
| SapanisertibAlso: INK-128, INK128, MLN-0128, MLN0128Given PO | Drug | Arm I (sapanisertib before and after surgery), Arm II (sapanisertib after surgery) |
| Therapeutic Conventional SurgeryUndergo surgery | Procedure or surgery | Arm I (sapanisertib before and after surgery), Arm II (sapanisertib after surgery) |
Primary outcome
Proportion of patients who achieve a drug concentration >= 70 nM in contrast enhancing tumor tissue
Time frame: Up to 2 years
The proportion of patients who achieve a drug concentration >= 70 nM in contrast enhancing tumor tissue will be calculated and the 90% confidence interval will be estimated using binomial distribution.
Difference in ratio of the S6 phosphorylation over the total between the two groups
Time frame: Up to 2 years
Two sample t-test will be used for the hypothesis testing of a difference in ratio of the S6 phosphorylation over the total between the two groups.
Difference of the pS6 concentration between the two groups
Time frame: Up to 2 years
Two sample t-test will be used for the hypothesis testing of a difference in ratio of the S6 phosphorylation over the total between the two groups. A "heat map" or "heat map visualization" may also be used to present and examine possible difference in clustering signaling pathway activation between the groups.
8 secondary outcomes
Sapanisertib concentration in non-enhancing tumor
Time frame: Up to 2 years
Sapanisertib concentration in blood
Time frame: Up to 2 years
Inhibition TORC1/2 in the non-enhancing components of the tumor as determined by modulation of RPS6 pS235 in reverse phase protein array (RPPA) assays
Time frame: Up to 2 years
Pharmacodynamic marker such as pS6 (by immunohistochemistry), p4EBP, pmTOR, and AKTpSer473 compared to the control
Time frame: Up to 2 years
Incidence of toxicity graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0
Time frame: Up to 30 days
Tumor response
Time frame: Up to 2 years
Progression-free survival (PFS)
Time frame: Time from date of post-surgical treatment start to the date progressive disease was defined, assessed up to 2 years
Overall survival (death)
Time frame: Time from the date of post-surgical treatment start to the date death occurred, assessed up to 2 years
Results and safety
The study was stopped early (reason given: Other - Lapse in funding). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Apr 2024.
- Derived from this study: PubMed 32597469Arnold A, Rodriguez F, Eberhart CG, Raabe EH. Response to letter to the editor: "All models are wrong; some models are useful". Neuro Oncol. 2020 Sep 29;22(9):1406-1407. doi: 10.1093/neuonc/noaa137. No abstract available.
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Recurrent Glioblastoma, IDH-Wildtype, Recurrent MGMT-Methylated Glioblastoma
Active, not recruitingPhase 1
Oral Gallium Maltolate for the Treatment of Relapsed and Refractory Glioblastoma
Glioblastoma
RecruitingPhase 1/2
PLX038 in Primary Central Nervous System Tumors Containing MYC or MYCN Amplifications
Glioma, Medulloblastoma
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.
Eudocia Q Lee principal investigator
National Cancer Institute (NCI)
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Laboratory Biomarker Analysis, Pharmacological Study and Sapanisertib in people with Glioblastoma and Gliosarcoma, run by National Cancer Institute (NCI) at 10 sites in United States.
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 31 inclusion and 23 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: stopped early, as of the sponsor's last update on 4 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States. 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 stopped early (reason given: Other - Lapse in funding). Results are not available in the source record.
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?
Proportion of patients who achieve a drug concentration >= 70 nM in contrast enhancing tumor tissue (time frame: Up to 2 years). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02133183, which also lists 1 linked publication.
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 4 Apr 2024.