INdividualized Screening Trial of Innovative Glioblastoma Therapy (INSIGhT)

NCT02977780 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 16-443
• Study Type: interventional
• Target: 460
• Locations: 1 country
• Sites: 12

Brief Summary

This research study is studying several investigational drugs as a possible treatment for Glioblastoma (GBM). The drugs involved in this study are :

• Abemaciclib (arm is currently closed to accrual)
• Temozolomide (temodar)
• Neratinib (arm is currently closed to accrual)
• CC115 (arm is currently closed to accrual)
• QBS10072S

Conditions

Glioblastoma

Keywords

Glioblastoma

Outcome Measures

Primary Outcomes (1)

• Overall Survival in Experimental Arms Compared with Standard Therapy

  2 years

Secondary Outcomes (4)

• Incidence of Treatment-Emergent Adverse Events

  2 years

• Progression Free Survival Among Experimental Arms And Biomarker Groups

  2 years

• Overall Survival Among Experimental Arms And Biomarker Groups

  2 years

• Association Between Progression Free Survival and Overall Survival Effects Of Experimental Agents

  2 years

Study Arms (5)

Temozolomide

ACTIVE COMPARATOR

* Daily Radiation for a maximum of 49 days. * Temozolomide will be administered orally on a daily dosing schedule * Temozolomide will be administered approximately 2-3 hours before each session of radiotherapy * Temozolomide will also be administered post radiation for up to 6 cycles (5 days/cycle)

Drug: Temozolomide

Neratinib with Temozolomide

EXPERIMENTAL

* Daily Radiation for a maximum of 49 days. * Temozolomide will be administered orally on a daily dosing schedule * Temozolomide will be administered approximately 2-3 hours before each session of radiotherapy * Neratinib will be taken post radiation at a daily oral pre-determine dose

Drug: Temozolomide; Drug: Neratinib

QBS10072S

EXPERIMENTAL

Daily Radiation for a maximum of 49 days. QBS10072S will be administered on Day 1 of Radiation Treatment QBS10072S will be administered post- radiation for up to 6 cycles

Drug: QBS10072S

Abemaciclib with Temozolomide

EXPERIMENTAL

* Daily Radiation for a maximum of 49 days. * Temozolomide will be administered orally on a daily dosing schedule during radiation * Temozolomide will be administered approximately 2-3 hours before each session of radiotherapy * Abemaciclib will be taken post radiation at a twice daily oral pre-determined dose

Drug: Temozolomide; Drug: Abemaciclib

CC-115

EXPERIMENTAL

* Twice daily oral dosing of CC-115 * Daily Radiation for a maximum of 49 days * CC115 will also be taken twice daily post radiation

Drug: CC-115

Interventions

Temozolomide DRUG

Temzolomide capsules

Also known as: Temodar

Abemaciclib with Temozolomide; Neratinib with Temozolomide; Temozolomide

Neratinib DRUG

Neratinib tablets

Neratinib with Temozolomide

QBS10072S DRUG

QBS10072S administered intravenously

QBS10072S

Abemaciclib DRUG

Abemaciclib tablets

Abemaciclib with Temozolomide

CC-115 DRUG

CC-115 tablets

CC-115

Eligibility Criteria

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

You may qualify if:

• Participants must have histologically confirmed intracranial glioblastoma or gliosarcoma following maximum surgical resection. Tumors primarily localized in the infratentorial compartment will be excluded.
• Participants may have had prior surgery for glioblastoma or gliosarcoma but no systemic or radiation therapy.
• Age ≥ 18 years.
• Karnofsky performance status ≥60
• Participants must have normal organ and marrow function as defined below:
• Leukocytes ≥3,000/mL
• Absolute neutrophil count ≥1,500/mL
• Platelets ≥100,000/mL
• Hemoglobin ≥ 9g/dl
• Total bilirubin within normal institutional limits (except for participant's with Gilbert's disease)
• AST(SGOT)/ALT(SGPT) ≤ 2.5 × institutional upper limit of normal
• Creatinine ≤ institutional upper limit of normal OR
• Creatinine clearance ≥ 60 mL/min/1.73 m2 for participants with creatinine levels above institutional normal.
• Potassium within normal institutional range, or correctable with supplements
• Serum amylase ≤ 1.5 x institutional upper limit of normal

You may not qualify if:

• Participants will not be eligible if the original diagnosis was a lower grade glioma and a subsequent histologic diagnosis revealed glioblastoma.
• Planned major surgery.
• Participants who are receiving any other investigational agents.
• Participants who have had any prior cranial radiotherapy.
• Planned use of Optune™.
• History of a different malignancy, unless (a) have been disease-free for at least 2 years and are deemed by the investigator to be at low risk for recurrence of that malignancy, and/or (b) malignancy was cervical cancer in situ, superficial bladder cancer or basal cell or squamous cell carcinoma of the skin, and malignancy has been treated. Patients who meet the above listed criteria and are only on preventative treatment will be deemed eligible.
• History of intratumoral or peritumoral hemorrhage if deemed significant by the treating physician.
• Impaired cardiac function or clinically significant cardiac diseases, including any of the following:
• Active uncontrolled cardiac disease, including cardiomyopathy, congestive heart failure (New York Heart Association functional classification of ≥2), unstable angina, myocardial infarction within 12 months of enrollment, or ventricular arrhythmia.
• Known history of congenital QT prolongation or Torsade de pointes (TdP).
• Complete left bundle branch or bifascicular block.
• QTc interval \> 450 ms for men or \> 470 ms for women.
• Persistent or history of clinically meaningful ventricular arrhythmias or atrial fibrillation.
• Unstable pectoris or myocardial infarction ≤ 3 months prior to starting study treatment.
• Uncontrolled hypertension (blood pressure ≥ 160/95 mmHg).

Sponsors & Collaborators

• Patrick Wen, MD: lead
• Eli Lilly and Company: collaborator
• Celgene: collaborator
• Puma Biotechnology, Inc.: collaborator
• Accelerate Brain Cancer Cure: collaborator
• Quadriga Biosciences, Inc.: collaborator

Study Sites (12)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

ACTIVE NOT RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

RECRUITING

Mayo Clinic

Rochester, Minnesota, 55905, United States

ACTIVE NOT RECRUITING

Columbia University Medical Center

New York, New York, 10032, United States

ACTIVE NOT RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

Cleveland Clinic

Cleveland, Ohio, 44195, United States

ACTIVE NOT RECRUITING

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15232, United States

RECRUITING

Lifespan / Rhode Island Hospital

Providence, Rhode Island, 02903, United States

ACTIVE NOT RECRUITING

UT MD Anderson Cancer Center

Houston, Texas, 77030, United States

COMPLETED

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

ACTIVE NOT RECRUITING

University of Virginia Health System

Charlottesville, Virginia, 22908, United States

COMPLETED

Related Publications (2)

• Rahman R, Trippa L, Lee EQ, Arrillaga-Romany I, Fell G, Touat M, McCluskey C, Wiley J, Gaffey S, Drappatz J, Welch MR, Galanis E, Ahluwalia MS, Colman H, Nabors LB, Hepel J, Elinzano H, Schiff D, Chukwueke UN, Beroukhim R, Nayak L, McFaline-Figueroa JR, Batchelor TT, Rinne ML, Kaley TJ, Lu-Emerson C, Mellinghoff IK, Bi WL, Arnaout O, Peruzzi PP, Haas-Kogan D, Tanguturi S, Cagney D, Aizer A, Doherty L, Lavallee M, Fisher-Longden B, Dowling S, Geduldig J, Watkinson F, Pisano W, Malinowski S, Ramkissoon S, Santagata S, Meredith DM, Chiocca EA, Reardon DA, Alexander BM, Ligon KL, Wen PY. Inaugural Results of the Individualized Screening Trial of Innovative Glioblastoma Therapy: A Phase II Platform Trial for Newly Diagnosed Glioblastoma Using Bayesian Adaptive Randomization. J Clin Oncol. 2023 Dec 20;41(36):5524-5535. doi: 10.1200/JCO.23.00493. Epub 2023 Sep 18.

  PMID: 37722087 DERIVED

• Groot J, Ott M, Wei J, Kassab C, Fang D, Najem H, O'Brien B, Weathers SP, Matsouka CK, Majd NK, Harrison RA, Fuller GN, Huse JT, Long JP, Sawaya R, Rao G, MacDonald TJ, Priebe W, DeCuypere M, Heimberger AB. A first-in-human Phase I trial of the oral p-STAT3 inhibitor WP1066 in patients with recurrent malignant glioma. CNS Oncol. 2022 Jun 1;11(2):CNS87. doi: 10.2217/cns-2022-0005. Epub 2022 May 16.

  PMID: 35575067 DERIVED

MeSH Terms

Conditions

Glioblastoma

Interventions

Temozolomide; neratinib; abemaciclib; 1-ethyl-7-(2-methyl-6-(1H-1,2,4-triazol-3-yl)pyridin-3-yl)-3,4-dihydropyrazino(2,3-b)pyrazin-2(1H)-one

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

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Patrick Y Wen, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Patrick Y Wen, MD

CONTACT

617-632-2166; patrick_wen@dfci.harvard.edu

Lisa Doherty, NP

CONTACT

617-632-2166; lisa_doherty@dfci.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director, Center for Neuro-Oncology

Model Details: This research study is studying several investigational drugs as a possible treatment for Glioblastoma (GBM). The drugs involved in this study are: Abemaciclib: start date= 12/9/2017 Temozolomide (temodar): start date= 12/9/2017 Neratinib: start date= 12/9/2017 CC115: start date= 12/9/2017 QBS10072S: start date= 12/13/2022

Study Record Dates

• First Submitted: November 18, 2016
• First Posted: November 30, 2016
• Study Start: February 9, 2017
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): April 30, 2028
• Last Updated: November 10, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (12)