Sapanisertib Before and After Surgery in Treating Patients With Recurrent Glioblastoma

NCT02133183 | Terminated Phase 1

• 5 other identifiers: NCI-2014-00907ABTC-13011301U01CA137443UM1CA137443
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 10

Brief 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. Sapanisertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Conditions

Glioblastoma; Gliosarcoma

Outcome Measures

Primary Outcomes (3)

• 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.

  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.

  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.

  Up to 2 years

Secondary Outcomes (8)

• Sapanisertib concentration in non-enhancing tumor

  Up to 2 years

• Sapanisertib concentration in blood

  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

  Up to 2 years

• Pharmacodynamic marker such as pS6 (by immunohistochemistry), p4EBP, pmTOR, and AKTpSer473 compared to the control

  Up to 2 years

• Incidence of toxicity graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0

  Up to 30 days

Other Outcomes (3)

• MSI from treated versus (vs) untreated enhancing and non- enhancing tumor

  Up to 2 years

• Ex-vivo sensitivity of tumor sphere cultures established from surgical specimens to sapanisertib, defined by a minimum of 20% reduction in cell proliferation as measured by cell titer glow in the sapanisertib group compared to the untreated group

  Up to 2 years

• Tumor genotype

  Up to 2 years

Study Arms (2)

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.

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.

Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Drug: Sapanisertib; Procedure: Therapeutic Conventional Surgery

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm I (sapanisertib before and after surgery); Arm II (sapanisertib after surgery)

Pharmacological Study OTHER

Correlative studies

Arm I (sapanisertib before and after surgery); Arm II (sapanisertib after surgery)

Sapanisertib DRUG

Given PO

Also known as: INK-128, INK128, MLN-0128, MLN0128, TAK-228

Arm I (sapanisertib before and after surgery); Arm II (sapanisertib after surgery)

Therapeutic Conventional Surgery PROCEDURE

Undergo surgery

Arm I (sapanisertib before and after surgery); Arm II (sapanisertib after surgery)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• weeks from the completion of radiation
• weeks from a nitrosourea chemotherapy or mitomycin C
• weeks from a non-nitrosourea chemotherapy
• weeks from any investigational (not Food and Drug Administration \[FDA\]-approved) agents
• weeks from administration of a non-cytotoxic, FDA-approved agent except bevacizumab/vascular endothelial growth factor receptor (VEGFR) inhibitors (e.g., erlotinib, hydroxychloroquine, etc.)
• 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)

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (10)

University of Alabama at Birmingham Cancer Center

Birmingham, Alabama, 35233, United States

Location

UCLA / Jonsson Comprehensive Cancer Center

Los Angeles, California, 90095, United States

Location

UCSF Medical Center-Parnassus

San Francisco, California, 94143, United States

Location

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

Location

Case Western Reserve University

Cleveland, Ohio, 44106, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, 15232, United States

Location

Related Publications (1)

• 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.

  PMID: 32597469 DERIVED

MeSH Terms

Conditions

Glioblastoma; Gliosarcoma

Interventions

sapanisertib

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Eudocia Q Lee

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 6, 2014
• First Posted: May 7, 2014
• Study Start: July 2, 2014
• Primary Completion: January 31, 2020
• Study Completion: October 31, 2023
• Last Updated: April 4, 2024

Record last verified: 2024-04

Locations

US (10)