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INdividualized Screening Trial of Innovative Glioblastoma Therapy (INSIGhT)

This study is currently recruiting participants.
Verified October 2017 by Brian Alexander, MD, Dana-Farber Cancer Institute
Sponsor:
ClinicalTrials.gov Identifier:
NCT02977780
First Posted: November 30, 2016
Last Update Posted: October 24, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborators:
Eli Lilly and Company
Celgene
Puma Biotechnology, Inc.
Accelerate Brain Cancer Cure
Information provided by (Responsible Party):
Brian Alexander, MD, Dana-Farber Cancer Institute
  Purpose

This research study is studying several investigational drugs as a possible treatment for Glioblastoma (GBM).

The drugs involved in this study are :

  • Abemaciclib
  • Temozolomide (temodar)
  • Neratinib
  • CC115

Condition Intervention Phase
Glioblastoma Drug: Temozolomide Drug: Neratinib Drug: CC-115 Drug: Abemaciclib Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: INdividualized Screening Trial of Innovative Glioblastoma Therapy (INSIGhT)

Resource links provided by NLM:


Further study details as provided by Brian Alexander, MD, Dana-Farber Cancer Institute:

Primary Outcome Measures:
  • Overall Survival in Experimental Arms Compared with Standard Therapy [ Time Frame: 2 years ]

Secondary Outcome Measures:
  • Incidence of Treatment-Emergent Adverse Events [ Time Frame: 2 years ]
    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.

  • Progression Free Survival Among Experimental Arms And Biomarker Groups [ Time Frame: 2 years ]
  • Overall Survival Among Experimental Arms And Biomarker Groups [ Time Frame: 2 years ]
  • Association Between Progression Free Survival and Overall Survival Effects Of Experimental Agents [ Time Frame: 2 years ]

Estimated Enrollment: 280
Actual Study Start Date: February 9, 2017
Estimated Study Completion Date: May 2021
Estimated Primary Completion Date: May 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Temozolomide
  • 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
Temzolomide capsules
Other Name: Temodar
Experimental: Abemaciclib with Temozolomide
  • 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
Temzolomide capsules
Other Name: Temodar
Drug: Abemaciclib
Abemaciclib capsules
Other Name: LY2835219
Experimental: CC-115
  • 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
CC-115 capsule
Other Name: CC0483115
Experimental: Neratinib with Temozolomide
  • 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
Temzolomide capsules
Other Name: Temodar
Drug: Neratinib
Neratinib tablets

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 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 for any diseases.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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
    • 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.

Exclusion Criteria:

  • 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).
  • 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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02977780


Contacts
Contact: Brian Alexander, MD MPH 617-732-7560 Brian_Alexander@dfci.harvard.edu
Contact: Sarah Gaffey 617-632-4341 sarah_gaffey@dfci.harvard.edu

Locations
United States, Alabama
University of Alabama at Birmingham Not yet recruiting
Birmingham, Alabama, United States, 35294
Contact: L. Burt Nabors, MD    205-934-1432    bnabors@uab.edu   
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Isabel Arrillaga-Romany, MD PhD    617-724-8770    iarrillaga@mgh.harvard.edu   
Principal Investigator: Isabel Arrillaga-Romany, MD PhD         
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02115
Contact: Brian Alexander, MD MPH    617-732-7560    Brian_Alexander@dfci.harvard.edu   
Contact: Lisa Doherty, NP    617-632-2166    lisa_doherty@dfci.harvard.edu   
Principal Investigator: Brian Alexander, MD MPH         
United States, Minnesota
Mayo Clinic Not yet recruiting
Rochester, Minnesota, United States, 55905
Contact: Eva Galanis, MD    507-284-2511    galanis.evanthia@mayo.edu   
United States, New York
Columbia University Medical Center Not yet recruiting
New York, New York, United States, 10032
Contact: Andrew Lassman, MD    212-342-0571    abl7@cumc.columbia.edu   
United States, Ohio
Cleveland Clinic Recruiting
Cleveland, Ohio, United States, 44195
Contact: Manmeet Ahluwalia,, MD    216-444-6145    ahluwam@ccf.org   
United States, Pennsylvania
University of Pittsburgh Medical Center Recruiting
Pittsburgh, Pennsylvania, United States, 15232
Contact: Jan Drappatz, MD    412-864-7791    drappatzj@upmc.edu   
United States, Texas
UT MD Anderson Cancer Center Not yet recruiting
Houston, Texas, United States, 77030
Contact: John DeGroot, MD    713-745-3072    jdegroot@mdanderson.org   
United States, Utah
Huntsman Cancer Institute Recruiting
Salt Lake City, Utah, United States, 84112
Contact: Howard Colman, MD    801-587-4042    Howard.colman@hci.utah.edu   
United States, Virginia
University of Virginia Health System Recruiting
Charlottesville, Virginia, United States, 22908
Contact: David Schiff, MD    434-924-5610    Ds4jd@virginia.edu   
Sponsors and Collaborators
Dana-Farber Cancer Institute
Eli Lilly and Company
Celgene
Puma Biotechnology, Inc.
Accelerate Brain Cancer Cure
Investigators
Principal Investigator: Brian Alexander, MD MPH Dana-Farber Cancer Institute
  More Information

Responsible Party: Brian Alexander, MD, Director, CNS Radiation Oncology, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT02977780     History of Changes
Other Study ID Numbers: 16-443
First Submitted: November 18, 2016
First Posted: November 30, 2016
Last Update Posted: October 24, 2017
Last Verified: October 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Brian Alexander, MD, Dana-Farber Cancer Institute:
Glioblastoma

Additional relevant MeSH terms:
Glioblastoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Temozolomide
Dacarbazine
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents