Adavosertib for Gliosarcoma

Phase-Based Progress Estimates
1
Effectiveness
1
Safety
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center, New York, NY
Gliosarcoma+7 More
Adavosertib - Drug
Eligibility
< 65
All Sexes
What conditions do you have?
Select

Study Summary

This study is evaluating whether a drug called adavosertib can be safely given with radiation therapy to treat children with newly diagnosed diffuse intrinsic pontine gliomas.

See full description

Eligible Conditions

  • Gliosarcoma
  • Anaplastic Astrocytoma (AA)
  • Glioblastoma
  • Anaplastic Oligo-astrocytoma (AOA)
  • Diffuse Midline Glioma, H3 K27M-Mutant
  • Diffuse Intrinsic Pontine Glioma

Treatment Effectiveness

Effectiveness Progress

1 of 3

Other trials for Gliosarcoma

Study Objectives

This trial is evaluating whether Adavosertib will improve 2 primary outcomes and 5 other outcomes in patients with Gliosarcoma. Measurement will happen over the course of Baseline to day 8.

Baseline to day 8
Change in p-CDC2, p-HH3 and gamma-H2AX expression
Day 8
Pharmacokinetic (PK) parameters of adavosertib
Up to 4 years
Incidence and grade of adverse events
Overall survival (OS)
Progression-free survival (PFS)
Response rate (partial response, complete response, or stable disease)
Up to 42 days
Maximum tolerated dose (MTD)

Trial Safety

Safety Progress

1 of 3

Other trials for Gliosarcoma

Trial Design

1 Treatment Group

Treatment (adavosertib, radiation therapy)
1 of 1
Experimental Treatment

This trial requires 46 total participants across 1 different treatment group

This trial involves a single treatment. Adavosertib is the primary treatment being studied. Participants will all receive the same treatment. There is no placebo group. The treatments being tested are in Phase 1 and are in the first stage of evaluation with people.

Treatment (adavosertib, radiation therapy)Patients undergo radiation therapy 5 days a week for 6 weeks (up to 30 fractions). Patients also receive adavosertib PO on days 1-5 of weeks 1, 3, and 5; days 1-5 of weeks 1, 3, and 5 AND days 1, 3, and 5 of weeks 2, 4, and 6; OR days 1-5 of weeks 1-6 depending on dose level assignment. Treatment continues in the absence of disease progression or unacceptable toxicity.
Treatment
First Studied
Drug Approval Stage
How many patients have taken this drug
Radiation Therapy
2005
Completed Phase 3
~7080
MK-1775
Not yet FDA approved

Trial Logistics

Trial Timeline

Approximate Timeline
Screening: ~3 weeks
Treatment: Varies
Reporting: up to 4 years
This trial has the following approximate timeline: 3 weeks for initial screening, variable treatment timelines, and roughly up to 4 years for reporting.

Closest Location

NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center - New York, NY

Eligibility Criteria

This trial is for patients born any sex aged 65 and younger. You must have received newly diagnosed for Gliosarcoma or one of the other 7 conditions listed above. There are 10 eligibility criteria to participate in this trial as listed below.

Mark “yes” if the following statements are true for you:
Patients with newly diagnosed DIPGs, defined as tumors with a pontine epicenter and diffuse involvement of the pons, are eligible without histologic confirmation
Patients with brainstem tumors that do not meet these criteria or are not considered to be typical intrinsic pontine gliomas will only be eligible if the tumors are biopsied and proven to be an anaplastic astrocytoma, glioblastoma, gliosarcoma, diffuse midline glioma with histone H3 K27M mutation, or anaplastic mixed glioma; patients with pilocytic astrocytoma, fibrillary astrocytoma, gangliogliomas, or other mixed gliomas without anaplasia are not eligible
Patients with disseminated disease are not eligible, and magnetic resonance imaging (MRI) of spine must be performed if disseminated disease is suspected by the treating physician
Enrollment must be no later than 28 days after the date of radiographic diagnosis or surgery, whichever is the later date
Patients must have a body surface area >= 0.35 m^2 at the time of study enrollment
Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50 for patients =< 16 years of age; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
Patients must not have received any prior anti-cancer therapy such as chemotherapy, radiation therapy, immunotherapy or bone marrow transplant for the treatment of DIPG; prior dexamethasone and/or surgery are allowed
Peripheral absolute neutrophil count (ANC) >= 1000/mm^3
Platelet count >= 100,000/mm^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)
Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or 0.8 mg/dL (3 to < 6 years of age)

Patient Q&A Section

How many people get diffuse intrinsic pontine glioma a year in the United States?

"An estimated 0.05 per 10,000 people in the U.S. is diagnosed with diffuse intrinsic pontine glioma; the most common age at detection is 63 and most common signs are nonspecific headache and vomiting. The incidence of diffuse intrinsic pontine glioma has increased markedly in recent years in the U.S. This report highlights the importance of further studies to identify the most common genetic drivers of diffuse intrinsic pontine gliomas, the role of the "one-hit" hypothesis, and the impact of radiation exposure on the risk of diffuse intrinsic pontine glioma a decade after childhood brain cancer diagnosis." - Anonymous Online Contributor

Unverified Answer

What causes diffuse intrinsic pontine glioma?

"DIPG affects younger patients and those with a family history of cancer. Both sexes and blacks have a greater risk of DIPG relative to whites and Asians, which is associated with an earlier age of diagnosis. Diagnosis of DIPG is difficult because of its clinical similarity to other brain tumors. For this reason, some clinicians question whether diagnosis-appropriate treatment is being provided to these patients." - Anonymous Online Contributor

Unverified Answer

What is diffuse intrinsic pontine glioma?

"DIPG was one of the most common primary brain tumors in western Canada, Alberta, occurring primarily in men in an age that mirrored that of its western counterparts. Further work to investigate epidemiology and risk factors for DIPG in different cultures is needed in order to prevent and treat this condition." - Anonymous Online Contributor

Unverified Answer

What are the signs of diffuse intrinsic pontine glioma?

"A small proportion of PGGs present without any history of seizure. Seizures are the most common signs in PGG. In pediatric and adult population, PGG is a rare differential diagnosis for focal seizures including focal cortical dysplasia, infarction, or metastasis. High grade dysplasia and medulloblastomas have similar patterns of brainstem compression and are common differential diagnoses along with PGG in children as well as adults. PGG in any age group usually presents with signs and symptoms of headache and a focal neurologic exam. PGG should be considered if focal neurologic symptoms occur in association with acute onset hemiparesis or hemiplegia." - Anonymous Online Contributor

Unverified Answer

What are common treatments for diffuse intrinsic pontine glioma?

"A variety of treatments exist for diffuse intrinsic pontine gliomas. These include radiation therapy, surgical resection, chemotherapy, targeted therapy that includes monoclonal antibodies and immunotherapy, and gene therapy." - Anonymous Online Contributor

Unverified Answer

Can diffuse intrinsic pontine glioma be cured?

"It is likely that most patients with diffuse intrinsic pontine gliomas that initially present as a low grade glioma will eventually relapse. However, the time to relapse seems to be a critical and independent factor in survival prognosis when diffuse intrinsic pontine gliomas are initially diagnosed within the pediatric set up. This can make diffuse intrinsic pontine gliomas a better indication for surgery than glioblastomas or medulloblastoma in the pediatric patient population. In those cases of relapse, it is possible to treat with a combination of surgery and radiation." - Anonymous Online Contributor

Unverified Answer

Have there been other clinical trials involving adavosertib?

"There has not been a single clinical trial investigating the efficacy of adavosertib. The role of adavosertib requires clarification before it can be placed into the first-line therapy. Future randomized phase III studies and/or new clinical trial data on patients with low-grade gliomas should be conducted." - Anonymous Online Contributor

Unverified Answer

How serious can diffuse intrinsic pontine glioma be?

"DSIPG is very, very serious. Only 5/8 of patients who are diagnosed with DSIPG survive for more than 1 year after diagnosis. No factors are associated with a longer overall survival in patients with DSIPG." - Anonymous Online Contributor

Unverified Answer

Does diffuse intrinsic pontine glioma run in families?

"The presence of DTIPGs in families of probands with these tumors suggests that a common molecular pathway might be involved. Further elucidation of the mechanism or pathways by which these tumors develop might result in the identification of a target for rational intervention." - Anonymous Online Contributor

Unverified Answer

Has adavosertib proven to be more effective than a placebo?

"ADV in DIPG patients showed an improvement in PFS and OS versus a placebo, with significant differences in OS and PFS at 8 weeks, suggesting that ADV should be further studied in DIPG patients as a treatment option." - Anonymous Online Contributor

Unverified Answer

How does adavosertib work?

"By inhibiting MAP1 kinase pathway, both in vitro and in vivo, AD may exert its therapeutic effects by preventing cell proliferation and differentiation, and inducing apoptosis. These features are shared with other MAP1 kinase pathway inhibitors, which suggests that AD may be a promising candidate for the treatment of DIPG." - Anonymous Online Contributor

Unverified Answer

What is the average age someone gets diffuse intrinsic pontine glioma?

"The average age at diagnosis of diffuse intrinsic pontine [oligodendroglioma](https://www.withpower.com/clinical-trials/oligodendroglioma) was 68 years, but it is rare among patients younger than 50 years. Results from a recent clinical trial imply that diffuse intrinsic pontine gliomas have a slower growth rate than oligodendrogliomas, particularly among patients younger than 50 years. The incidence of diffuse intrinsic pontine glioma is expected to increase by 6% for each year after age 50 years, reaching 27,000 by 2040. The incidence of other central nervous system tumors has increased significantly." - Anonymous Online Contributor

Unverified Answer
Please Note: These questions and answers are submitted by anonymous patients, and have not been verified by our internal team.
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