INCMGA00012 and Epacadostat in Combination With Radiation and Bevacizumab in Patients With Recurrent Gliomas

  • STATUS
    Recruiting
  • End date
    Apr 30, 2026
  • participants needed
    55
  • sponsor
    Washington University School of Medicine
Updated on 6 November 2021
measurable disease
karnofsky performance status
neutrophil count
blood transfusion
bevacizumab
aptt
glioblastoma multiforme
gliosarcoma
recurrent glioblastoma
immunotherapeutic agent

Summary

In this study, the investigators propose to combine INCMGA00012 with radiation therapy (RT) and bevacizumab with or without epacadostat in the treatment of recurrent glioblastoma (GBM). The investigators hypothesize that this combination provides a powerful synergy between RT and immune modulators to produce more robust anti-tumor immune response, induce tumor regression and improve overall survival.

Details
Condition glial tumor, Glioma, Glioblastoma Multiforme, glioblastoma, Glioblastoma multiforme, Gliomas
Treatment radiation therapy, bevacizumab, Peripheral blood draw, Epacadostat
Clinical Study IdentifierNCT03532295
SponsorWashington University School of Medicine
Last Modified on6 November 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Recurrent WHO grade IV glioblastoma or gliosarcoma, including molecular features of glioblastoma
Other GBM variants and "secondary GBM" are allowed. IDH-mutant GBM that have relapsed more than once may be included, as the prognosis of multiply recurrent GBM patients may not differ based on IDH mutation status
Disease must have recurred and patient must be a candidate for re-irradiation and bevacizumab. Any number of recurrences are allowed
Patients must have measurable disease per RANO criteria. Lesions will be considered measurable when they are bi-dimensional with clearly defined margins of 5 mm in two perpendicular diameters
At least 18 years of age
Prior transient use of bevacizumab for cerebral edema or radiation necrosis is allowed without a washout period. Prior bevacizumab use is permitted if used for treatment of disease if administered more than 6 months prior to registration
Karnofsky performance status 60%
Normal bone marrow and organ function as defined below
Absolute neutrophil count 1,000/mcL
Platelets 75,000/mcL
Hemoglobin 9.0 g/dL or > 5.6 mmol/L (transfusion is acceptable to meet this criterion)
Serum creatinine ULN or creatinine clearance 60 mL/min/1.73 m2 by Cockcroft-Gault for patients
Serum total bilirubin 1.5 ULN
AST(SGOT)/ALT(SGPT) 2.5 x IULN
INR or PT 1.5 x IULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
aPTT 1.5 x IULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
At least 28 days from any major surgery such as craniotomy and surgical wound is fully healed, and at least 14 days from LITT or biopsy. Prior to surgery, there must be imaging evidence of measurable progressive disease (PD) per RANO criteria and noted above
Women of childbearing potential and men must agree to use highly effective contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately
Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable)

Exclusion Criteria

Currently receiving any other investigational agents
A history of allergic reactions attributed to compounds of similar chemical or biologic composition to epacadostat, avelumab, bevacizumab, or other agents used in the study
Dexamethasone dose > 4 mg daily at the time of registration (higher dose of steroid for symptom control is allowed during the study)
History of intracranial abscess within 6 months prior to start of study therapy
Has active autoimmune disease or syndrome (i.e. moderate or severe rheumatoid arthritis, moderate or severe psoriasis, multiple sclerosis, active inflammatory bowel disease) that has required systemic treatment in the past 2 years (i.e. with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs) or who are receiving systemic therapy for an autoimmune or inflammatory disease (i.e. with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment. Subjects are permitted to enroll if they have vitiligo, resolved childhood asthma/atopy, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger
Has a severe acute or chronic medical condition including immune colitis, inflammatory bowel disease, immune pneumonitis, pulmonary fibrosis, or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior, or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study
Has had an allogeneic tissue/solid organ transplant
Has an active infection requiring intravenous antibiotic therapy. Has a known history of active tuberculosis (TB; bacillus tuberculosis)
Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, or IDO inhibitor
If a patient is enrolled to regimen B, they are prohibited from receiving monoamine oxidase inhibitors (MAOIs) or drug which has significant MAOI activity (meperidine, linezolid, methylene blue) within the 21 days before screening
If a patient is enrolled to regimen B, the use of any UGT1A9 inhibitor from screening through follow-up period, including acitretin, amitriptyline, androsterone, cyclosporine, dasatinib, diclofenac, diflunisal, efavirenz, erlotinib, estradiol (17-beta), flutamide, gefitinib, gemfibrozil, glycyrrhetinic acid, glycyrrhizin, imatinib, imipramine, ketoconazole, linoleic acid supplements, mefenamic acid, mycophenolic acid, niflumic acid, nilotinib, phenobarbital, phenylbutazone, phenytoin, probenecid, propofol, quinidine, ritonavir, sorafenib, sulfinpyrazone, valproic acid, and verapamil is prohibited
Any history of serotonin syndrome (SS) after receiving serotonergic drugs
If a patient is enrolled to regimen B, the use of probiotics from screening through end of treatment is prohibited
Has uncontrolled HIV (HIV 1/2 antibodies). Well-controlled HIV is defined as CD4+ count > 300 cells, undetectable viral load, and receiving HAART/ART. Study specific HIV testing is not required for patients who do not have any prior history of HIV
If a patient is enrolled to regimen B, the use of warfarin is prohibited. If anti-coagulation is needed during the conduct of the study and non-warfarin regimens are not feasible, the participant must discontinue study therapy
Chronic use of systemic antibiotics (> 14 days) unless medical monitor review and approval
Uncontrolled intercurrent illness including, but not limited to, clinically significant (i.e. active) cardiovascular disease: cerebral vascular accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 60 months prior to enrollment), congestive heart failure ( NYHA class II), unstable angina pectoris, or serious cardiac arrhythmia requiring medication
Due to the potential concern for epacadostat metabolite inhibition of CYP1A2, CYP2C8 and CYP2C19, OATP1B1 and OATPIB3 transporters with doses of epacadostat greater than 300 mg BID (eg 400 mg BID or 600 mg BID), the medications will be prohibited for concomitant use
History or presence of an abnormal electrocardiogram (ECG) that, in the investigator's opinion, is clinically meaningful. Screening QTc interval > 480 msec will require investigator's evaluation on patient's eligibility. Subjects with left bundle branch block are excluded
Presence of a gastrointestinal condition that may affect drug absorption
Receipt of live attenuated vaccine within 30 days before the first dose of study treatment. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, yellow fever, rabies, Bacillus Calmette-Gurin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g. FluMist) are live attenuated vaccines and are not allowed
Has uncontrolled active hepatitis B (e.g., HBsAg reactive or HBV DNA detected by quant RT PCR) or hepatitis C (e.g. HCsAg reactive or HCV RNA [qualitative or quantitative] is detected)
Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test prior to the start of study treatment
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact

site

0/250

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Browse trials for

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note