AzTrials
AzTrials

GlioblastomaPhase 2NCT02977780

INdividualized Screening Trial of Innovative Glioblastoma Therapy (INSIGhT)

A Phase 2 study testing Temozolomide, Neratinib and QBS10072S in people with Glioblastoma, run by David Reardon, MD at 12 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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 Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Glioblastoma
What is being tested?
Temozolomide, Neratinib and QBS10072S
Could I receive a placebo?
No, everyone receives an active treatment
How many people
460 participants
Where
12 sitesUnited States
Study dates
9 Feb 2017to 30 Apr 2028
Phase
Phase 2
Are there results?
Not yet: the study is under way

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

  • 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
Show all 27Show fewer
  • 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
  • Serum lipase ≤ 1.5 x institutional upper limit of normal
  • INR < 2.0
  • PTT ≤ institutional upper limit of normal, unless receiving therapeutic low molecular weight heparin
  • Must be able to swallow pills.
  • Participants must plan to begin radiation therapy 14-42 days after surgical resection.
  • Immunohistochemically negative for IDH1 R132H mutation.
  • Evidence that the tumor MGMT promoter is unmethylated by standard of care assays.
  • Genotyping data available or in process (data must be available at time of initial registration if randomization probabilities differ across biomarker subgroups as determined by the DFCI Coordinating Center) to assign biomarker subgroups through whole exome sequencing, whole genome copy number analysis, or a combination as described in Section 9.1.
  • MRI with gadolinium should be obtained within 21 days prior to beginning treatment. Patients without measurable disease are eligible. Participants must be able to undergo MRIs (CTs are not allowed for response assessment on study).
  • The effects of the experimental agents used in this study on the developing human fetus are unknown. For this reason and because other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential (women who are not free from menses for > 2 years, post hysterectomy/oophorectomy, or surgically sterilized) and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation unless otherwise specified in sub-study that the participant is randomized to. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
  • For women of child bearing potential (women who are not free from menses for > 2 years, post hysterectomy/oophorectomy, or surgically sterilized) a negative serum pregnancy test must be documented prior to initial registration.
  • Ability to understand and the willingness to sign a written informed consent document.

Who cannot join

  • 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.
Show all 31Show fewer
  • 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).
  • Other clinically significant heart disease such as congestive heart failure requiring treatment.
  • Uncontrolled diabetes mellitus, or subjects with either of the following:
  • Fasting blood glucose (FBG defined as fasting for at least 8 hours) ≥ 200 mg/dL (7.0 mmol/L), or
  • HbA1c ≥ 8%
  • Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, chronic liver disease (e.g., cirrhosis, hepatitis), chronic renal disease, pancreatitis, chronic pulmonary disease, or psychiatric illness/social situations that would limit compliance with study requirements. Subjects must be free of any clinically relevant disease (other than glioma) that would, in the treating investigator's opinion, interfere with the conduct of the study or study evaluations.
  • Known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNS [qualitative] is detected).
  • Known acute or chronic pancreatitis.
  • Participants with active diarrhea ≥ CTCAE grade 2 despite medical management.
  • Active infection requiring antibiotics.
  • Pregnant or breastfeeding.
  • Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or extensive small bowel resection). Participants with unresolved diarrhea ≥ CTCAE grade 2 will be excluded as previously indicated.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to any of the experimental agents or other agents used in study.
  • Participants taking an enzyme-inducing anti-epileptic drug (EIAED): phenobarbital, phenytoin, fosphenytoin, primidone, carbamazepine, oxcarbazepine, eslicarbazepine, rufinamide, and felbamate. Participant must be off any EIAEDs for at least 7 days prior to planned start of study treatment. A list of EIAED and other inducers of CYP3A4 is provided. Among non-EIAED, caution is recommended with use of valproic acid due to potential for drug interaction.
  • Participants taking a drug known to be strong inhibitors or inducers of isoenzyme CYP3A. Participant must be off CYP3A inhibitors and inducers for at least 7 days prior to planned start of study treatment. NOTE: participants must avoid consumption of Seville orange (and juice), grapefruit or grapefruit juice, grapefruit hybrids, pummelos and exotic citrus fruits from 7 days prior to planned start of study treatment and during the entire study treatment period due to potential CYP3A4 interaction.
  • Current use of herbal preparations/medications, including but not limited to: St. John's wort, Kava, ephedra (ma huang), gingko biloba, dehydroepiandrosterone (DHEA), yohimbe, saw palmetto, ginseng. Participants should stop using these herbal medications 7 days prior to planned start of study treatment.
  • Current use of warfarin sodium or any other coumadin-derivative anticoagulant. Participant must be off Coumadin-derivative anticoagulants for at least 7 days prior to planned start of study treatment. Low molecular weight heparin and factor Xa inhibitors are allowed.

Trial locations and contacts

12 sites in 1 country. Contact the study team or a site near you to ask about taking part.

David Y Reardon, MD contact

6176322166

David_Reardon@DFCI.HARVARD.EDU

David Reardon contact

6176322166

David_Reardon@DFCI.HARVARD.EDU

12 sites in 1 country

United States12 sites, 4 recruiting

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35294

    Active, not recruiting

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

    Isabel Arrillaga-Romany, MD PhD, 617-724-8770, iarrillaga@mgh.harvard.edu

    Isabel Arrillaga-Romany, MD PhD

    Recruiting

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02115

    David Y. Reardon, MD, 6176322166, David_Reardon@DFCI.HARVARD.EDU

    6176322166, David_Reardon@DFCI.HARVARD.EDU

    Recruiting

  • University of Virginia Health System

    Charlottesville, Virginia, 22908

    Completed

  • Cleveland Clinic

    Cleveland, Ohio, 44195

    Active, not recruiting

  • UT MD Anderson Cancer Center

    Houston, Texas, 77030

    Completed

  • Columbia University Medical Center

    New York, New York, 10032

    Active, not recruiting

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

    Thomas Kaley, MD, 212-639-5122, kaleyt@mskcc.org

    Recruiting

  • University of Pittsburgh Medical Center

    Pittsburgh, Pennsylvania, 15232

    Jan Drappatz, MD, 412-864-7791, drappatzj@upmc.edu

    Recruiting

  • Lifespan / Rhode Island Hospital

    Providence, Rhode Island, 02903

    Active, not recruiting

  • Mayo Clinic

    Rochester, Minnesota, 55905

    Active, not recruiting

  • Huntsman Cancer Institute

    Salt Lake City, Utah, 84112

    Active, not recruiting

Other trials in United States

About this study

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
Read the detailed description

This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational drug to learn whether the study drug works in treating a specific disease. "Investigational" means that the drug is being studied.

In this research study, the investigators are looking to compare the effects, good and bad, of the standard of care with the three investigational agent sub-studies Abemaciclib, Neratinib, CC115, QBS10072S to help people with Glioblastoma including the specific molecular changes in the genes and proteins.

The FDA has approved Temozolomide (temodar) as a treatment for this disease, however the FDA has not approved Abemaciclib, CC115, Neratinib, QBS10072S for any diseases.

Conditions
Glioblastoma
Being tested
Temozolomide, Neratinib, QBS10072S, Abemaciclib, CC-115
Keywords
Glioblastoma
Medical subject headings
Glioblastoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TemozolomideDrug

    Also called Temodar

    Temzolomide capsules

  • NeratinibDrug

    Neratinib tablets

  • QBS10072SDrug

    QBS10072S administered intravenously

  • AbemaciclibDrug

    Abemaciclib tablets

  • CC-115Drug

    CC-115 tablets

Study groups in NCT02977780
Study groupRoleWhat they receive
TemozolomideActive 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)
Receives: Drug: Temozolomide
Neratinib with TemozolomideExperimental* 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
Receives: Drug: Temozolomide; Drug: Neratinib
QBS10072SExperimentalDaily 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
Receives: Drug: QBS10072S
Abemaciclib with TemozolomideExperimental* 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
Receives: Drug: Temozolomide; Drug: Abemaciclib
CC-115Experimental* Twice daily oral dosing of CC-115 * Daily Radiation for a maximum of 49 days * CC115 will also be taken twice daily post radiation
Receives: Drug: CC-115

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall Survival in Experimental Arms Compared with Standard Therapy

    Measured: 2 years

Secondary outcomes (4)

  1. Incidence of Treatment-Emergent Adverse Events

    Safety will be assessed by quantifying the toxicities and grades experienced by subjects, including serious adverse events (SAEs). The following will also be measured as part of safety: laboratory safety assessments, KPS status, vital signs and physical examinations.

    Measured: 2 years

  2. Progression Free Survival Among Experimental Arms And Biomarker Groups

    Measured: 2 years

  3. Overall Survival Among Experimental Arms And Biomarker Groups

    Measured: 2 years

  4. Association Between Progression Free Survival and Overall Survival Effects Of Experimental Agents

    Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Nov 2016 (estimated)
  2. Study start9 Feb 2017
  3. Primary completion1 Feb 2028 (estimated)
  4. Study completion30 Apr 2028 (estimated)

Resources

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
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
Masking
None (open label)
Enrolment
460 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02977780
Sponsor's protocol ID
16-443
Status last verified
Aug 2026
First submitted
18 Nov 2016
Last updated
19 Aug 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Rudra Gupta T, Polley MC, Redd R, Lee EQ, Arrillaga-Romany I, Gilbert MR, Tan Y, Touat M, 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, Kaley TJ, Lu-Emerson C, Mellinghoff IK, Bi WL, Arnaout O, Peruzzi PP, Haas-Kogan D, Tanguturi S, Aizer A, Doherty L, Santagata S, Meredith DM, Chiocca EA, Reardon DA, Ligon KL, Weller M, Mehta MP, Wen PY, Trippa L, Rahman R. Treatment Effect Reanalysis of the Randomized Individual Screening Trial of Innovative Glioblastoma Therapy in Newly Diagnosed Glioblastoma With External Control Data. J Clin Oncol. 2026 Jul 20;44(21):2048-2058. doi: 10.1200/JCO-25-01586. Epub 2026 May 22.

    PubMed 42172567

  • 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.

    PubMed 37722087

  • 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.

    PubMed 35575067

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Temozolomide, Neratinib and QBS10072S in people with Glioblastoma, run by David Reardon, MD at 12 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 27 inclusion and 31 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: looking for participants now, as of the sponsor's last update on 19 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 12 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact David Y Reardon, MD (6176322166, David_Reardon@DFCI.HARVARD.EDU), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Survival in Experimental Arms Compared with Standard Therapy (time frame: 2 years). 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 NCT02977780, which also lists 3 linked publications.

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 Aug 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in