Adult Anaplastic AstrocytomaPhase 1NCT02186509
Alisertib and Fractionated Stereotactic Radiosurgery in Treating Patients With Recurrent High Grade Gliomas
A Phase 1 study testing Hyperfractionated radiation therapy, Stereotactic radiosurgery and Alisertib in people with Adult Anaplastic Astrocytoma and Adult Anaplastic Ependymoma, run by Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University at 1 site in United States.
Trial summary
This phase I trial studies the side effects and best dose of alisertib when combined with fractionated stereotactic radiosurgery in treating patients with high-grade gliomas that have returned after previous treatment with radiation therapy (recurrent). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Adult Anaplastic Astrocytoma, Adult Anaplastic Ependymoma, Adult Anaplastic Oligodendroglioma
- What is being tested?
- Hyperfractionated radiation therapy, Stereotactic radiosurgery and Alisertib
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 1 siteUnited States
- Study dates
- 30 Jan 2015to 31 Dec 2018
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Patients must have a previously histologically or cytologically confirmed high grade glioma (astrocytic or oligodendroglial supratentorial tumors grade 3 or 4) that has been previously treated with fractionated radiation therapy and now shows evidence of recurrence.
- Patients must have recovered from the toxic effects of prior therapy.
- Patients must have recovered from the effects of surgery. There must be a minimum of 21 days from the day of surgery to the day of protocol treatment. For core or needle biopsy, a minimum of 7 days must have elapsed prior to the day of protocol treatment.
- Prior treatment with cytotoxic and biological agents is permissible. There should be at least a 2-week break between prior treatment and the protocol treatment.
- Prior treatment with fractionated radiation therapy (up to 60Gy) is an eligibility criterion, however there should not have been a second course of fractionated radiotherapy to the supratentorial area.
- One prior single fraction radiosurgical procedure within the treatment field is acceptable if V12<5 cc (V12 is the volume of normal brain (outside GTV) receiving 12 or more Gy). Additional radiosurgical procedures outside of the treatment area are acceptable.
Show all 16Show fewer
- Subject must be able to take oral medication and to maintain a fast, is required for 2 hours before and 1 hour after MLN8237 administration.
- ANC > 1500/mm³, platelets > 100,000/mm³, Hgb > 9 g/dL. Values must be obtained without need for myeloid growth factor or platelet transfusion support within 14 days of registration. However, erythrocyte growth factor is allowed as per published ASCO guidelines.
- Total bilirubin ≤ ULN, SGOT (AST) and SGPT (ALT)< 1.5 x ULN, within 14 days of registration.
- Adequate renal function as defined by: calculated creatinine clearance must be ≥40 mL/minute (Cockcroft-Gault), within 14 days of registration.
- Age >18 years.
- ECOG performance status <2 (see Appendix I).
- Life expectancy of greater than 2 months.
- Women of childbearing potential must have a negative β-HCG pregnancy test documented within 7 days prior to registration.
- Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for 4 months after last dose.
- Ability to understand and the willingness to sign a written informed consent document.
Who cannot join
- Known history of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness such as severe chronic obstructive pulmonary disease requiring supplemental oxygen.
- Systemic infection requiring IV antibiotic therapy within 14 days preceding the first dose of study drug, or other severe infection.
- Myocardial infarction within 6 months prior to enrollment, New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at Screening has to be documented by the investigator as not medically relevant.
- Female subject is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum β-human chorionic gonadotropin (β-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
- Patient has received other investigational drugs within 14 days before enrollment
- Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
Show all 12Show fewer
- Other severe acute or chronic medical or psychiatric condition, including uncontrolled diabetes, malabsorption, resection of the pancreas or upper small bowel, requirement for pancreatic enzymes, any condition that would modify small bowel absorption of oral medications, or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for enrollment in this study.
- Treatment with clinically significant enzyme inducers, such as the enzyme-inducing antiepileptic drugs phenytoin, carbamazepine or phenobarbital, or rifampin, rifabutin, rifapentine or St. John's wort within 14 days prior to the first dose of MLN8237 and during the study.
- Known history of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C. Testing is not required in the absence of clinical findings or suspicion.
- Patients have a history of any other malignancy from which the patient has been disease-free for less than 2 years, with the exception of adequately treated basal or squamous cell carcinoma of skin, superficial bladder cancer or carcinoma in situ of cervix, AJCC (version 7.0) stage 0 or I breast cancer, AJCC (version 7.0) stage I, or II prostate cancer.
- Radiation therapy to more than 25% of the bone marrow. Whole pelvic radiation is considered to be over 25%.
- Patients who cannot swallow whole tablets (i.e. medication tablets)
Trial locations and contacts
1 site in 1 country.
United States1 site
Sidney Kimmel Cancer Center at Thomas Jefferson University
Philadelphia, Pennsylvania, 19107
About this study
Official title: Phase I Study of Alisertib With Concurrent Fractionated Stereotactic Radiation Treatment for Recurrent High Grade Gliomas
This phase I trial studies the side effects and best dose of alisertib when combined with fractionated stereotactic radiosurgery in treating patients with high-grade gliomas that have returned after previous treatment with radiation therapy (recurrent). Alisertib may stop the growth of tumor cells by blocking an enzyme needed for the cells to divide. Radiation therapy uses high energy x rays to kill tumor cells. Stereotactic radiosurgery uses special positioning equipment to send a single high dose of radiation directly to the tumor and cause less damage to normal tissue. Delivering stereotactic radiosurgery over multiple doses (fractionation) may cause more damage to tumor tissue than normal tissue while maintaining the advantage of its accuracy.
Read the detailed description
PRIMARY OBJECTIVES:
- Evaluate the safety and tolerability of the study treatment. II. To determine the maximum tolerated dose (MTD) of daily oral alisertib when combined with fractionated stereotactic radiation treatment for recurrent high grade glioma.
SECONDARY OBJECTIVES:
- To estimate 6 month progression free survival rate. II. To estimate the median time to progression. III. To estimate overall survival. IV. To estimate the impact on quality of life (QoL).
OUTLINE: This is a dose-escalation study of alisertib.
CONCURRENT PHASE: Patients undergo fractionated stereotactic radiosurgery once daily (QD) every weekday for 10 days and receive alisertib orally (PO) twice daily (BID) concurrently with radiation therapy for 10 days.
MAINTENANCE PHASE: Patients receive alisertib PO BID on days 1-7. Treatment repeats every 21 days for up to 18 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 1 year and then every 4-6 months thereafter.
- Conditions
- Adult Anaplastic Astrocytoma, Adult Anaplastic Ependymoma, Adult Anaplastic Oligodendroglioma, Adult Brain Stem Glioma, Adult Diffuse Astrocytoma, Adult Giant Cell Glioblastoma
- Being tested
- Hyperfractionated radiation therapy, Stereotactic radiosurgery, Alisertib, Quality-of-life assessment
- Medical subject headings
- Astrocytoma, Ependymoma, Oligodendroglioma, Glioblastoma, Gliosarcoma, Glioma, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hyperfractionated radiation therapyRadiation
Undergo hyperfractionated radiation therapy
Stereotactic radiosurgeryRadiation
Undergo stereotactic radiosurgery
AlisertibDrug
Also called MLN8237
Given PO
Quality-of-life assessmentProcedure or surgery
Ancillary studies
| Study group | Role | What they receive |
|---|---|---|
| Alisertib, fractionated stereotactic radiosurgery | Experimental | CONCURRENT PHASE: Patients undergo fractionated stereotactic radiosurgery QD every weekday for 10 days and receive alisertib PO BID concurrently with radiation therapy for 10 days.
MAINTENANCE PHASE: Patients receive alisertib PO BID on days 1-7. Treatment repeats every 21 days for up to 18 courses in the absence of disease progression or unacceptable toxicity. Receives: Radiation: Hyperfractionated radiation therapy; Radiation: Stereotactic radiosurgery; Drug: Alisertib; Procedure: Quality-of-life assessment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD) of Alisertib
Defined as the dose at which >= 2 patients experience dose-limiting toxicity, graded in severity according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
Measured: Up to 30 days after completion of radiation therapy
Secondary outcomes (3)
Number of Participants With Complete or Partial Response
95% confidence intervals will be computed. Response was defined by the Updated Response Assessment Criteria for High-Grade Gliomas: Response Assessment in Neuro-Oncology Work Group (RANO)
Measured: Up to 5 years
Number of Participants With Progression Free Survival at 6 Months
Estimated through the Kaplan-Meier method.
Measured: At 6 months
Number of Participants With Overall Survival at 6 Months
Estimated through the Kaplan-Meier method.
Measured: At 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jul 2014 (estimated)
- Study start30 Jan 2015
- Primary completion31 Mar 2017
- Study completion31 Dec 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Adult Anaplastic AstrocytomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University
- Sponsor type
- University, hospital or other
- Collaborators
- Millennium Pharmaceuticals, Inc.
- Responsible party
- Sponsor
- Investigators
- Wenyin Shi, MD, PhD, Principal investigator, Thomas Jefferson University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02186509
- Sponsor's protocol ID
- 13P.528
- Other IDs
- 2013-12, JT 3007
- Status last verified
- Apr 2025
- First submitted
- 7 Jul 2014
- Last updated
- 30 Apr 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Song A, Andrews DW, Werner-Wasik M, Kim L, Glass J, Bar-Ad V, Evans JJ, Farrell CJ, Judy KD, Daskalakis C, Zhan T, Shi W. Phase I trial of alisertib with concurrent fractionated stereotactic re-irradiation for recurrent high grade gliomas. Radiother Oncol. 2019 Mar;132:135-141. doi: 10.1016/j.radonc.2018.12.019. Epub 2019 Jan 4.
PubMed 30825962
Study at a glance
From the registry record, last updated by the sponsor on 30 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of Alisertib With Concurrent Fractionated Stereotactic Radiation Treatment for Recurrent High Grade Gliomas
- ClinicalTrials.gov ID
- NCT02186509
- Acronym / sponsor ID
- 13P.528
- Conditions
- Adult Anaplastic Astrocytoma, Adult Anaplastic Ependymoma, Adult Anaplastic Oligodendroglioma, Adult Brain Stem Glioma, Adult Diffuse Astrocytoma, Adult Giant Cell Glioblastoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson UniversityUniversity, hospital or other
- Collaborators
- Millennium Pharmaceuticals, Inc.
- Study start
- 30 Jan 2015 (actual)
- Primary completion
- 31 Mar 2017 (actual)
- Study completion
- 31 Dec 2018 (actual)
- First posted
- 10 Jul 2014 (estimated)
- Results
- Posted 9 Sep 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase I trial studies the side effects and best dose of alisertib when combined with fractionated stereotactic radiosurgery in treating patients with high-grade gliomas that have returned after previous treatment with radiation therapy (recurrent). Alisertib may stop the growth of tumor cells by blocking an enzyme needed for the cells to divide. Radiation therapy uses high energy x rays to kill tumor cells. Stereotactic radiosurgery uses special positioning equipment to send a single high dose of radiation directly to the tumor and cause less damage to normal tissue. Delivering stereotactic radiosurgery over multiple doses (fractionation) may cause more damage to tumor tissue than normal tissue while maintaining the advantage of its accuracy.
Detailed description
PRIMARY OBJECTIVES:
- Evaluate the safety and tolerability of the study treatment. II. To determine the maximum tolerated dose (MTD) of daily oral alisertib when combined with fractionated stereotactic radiation treatment for recurrent high grade glioma.
SECONDARY OBJECTIVES:
- To estimate 6 month progression free survival rate. II. To estimate the median time to progression. III. To estimate overall survival. IV. To estimate the impact on quality of life (QoL).
OUTLINE: This is a dose-escalation study of alisertib.
CONCURRENT PHASE: Patients undergo fractionated stereotactic radiosurgery once daily (QD) every weekday for 10 days and receive alisertib orally (PO) twice daily (BID) concurrently with radiation therapy for 10 days.
MAINTENANCE PHASE: Patients receive alisertib PO BID on days 1-7. Treatment repeats every 21 days for up to 18 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 1 year and then every 4-6 months thereafter.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Alisertib, fractionated stereotactic radiosurgery | Experimental | Radiation: Hyperfractionated radiation therapy, Radiation: Stereotactic radiosurgery, Drug: Alisertib, Procedure: Quality-of-life assessmentCONCURRENT PHASE: Patients undergo fractionated stereotactic radiosurgery QD every weekday for 10 days and receive alisertib PO BID concurrently with radiation therapy for 10 days. MAINTENANCE PHASE: Patients receive alisertib PO BID on days 1-7. Treatment repeats every 21 days for up to 18 courses in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Patients must have a previously histologically or cytologically confirmed high grade glioma (astrocytic or oligodendroglial supratentorial tumors grade 3 or 4) that has been previously treated with fractionated radiation therapy and now shows evidence of recurrence.
- Patients must have recovered from the toxic effects of prior therapy.
- Patients must have recovered from the effects of surgery. There must be a minimum of 21 days from the day of surgery to the day of protocol treatment. For core or needle biopsy, a minimum of 7 days must have elapsed prior to the day of protocol treatment.
- Prior treatment with cytotoxic and biological agents is permissible. There should be at least a 2-week break between prior treatment and the protocol treatment.
- Prior treatment with fractionated radiation therapy (up to 60Gy) is an eligibility criterion, however there should not have been a second course of fractionated radiotherapy to the supratentorial area.
Key exclusion criteria (12 listed)
- Known history of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness such as severe chronic obstructive pulmonary disease requiring supplemental oxygen.
- Systemic infection requiring IV antibiotic therapy within 14 days preceding the first dose of study drug, or other severe infection.
- Myocardial infarction within 6 months prior to enrollment, New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at Screening has to be documented by the investigator as not medically relevant.
- Female subject is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum β-human chorionic gonadotropin (β-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
- Patient has received other investigational drugs within 14 days before enrollment
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Hyperfractionated radiation therapyUndergo hyperfractionated radiation therapy | Radiation | Alisertib, fractionated stereotactic radiosurgery |
| Stereotactic radiosurgeryUndergo stereotactic radiosurgery | Radiation | Alisertib, fractionated stereotactic radiosurgery |
| AlisertibAlso: MLN8237Given PO | Drug | Alisertib, fractionated stereotactic radiosurgery |
| Quality-of-life assessmentAncillary studies | Procedure or surgery | Alisertib, fractionated stereotactic radiosurgery |
Primary outcome
Maximum Tolerated Dose (MTD) of Alisertib
Time frame: Up to 30 days after completion of radiation therapy
Defined as the dose at which >= 2 patients experience dose-limiting toxicity, graded in severity according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
3 secondary outcomes
Number of Participants With Complete or Partial Response
Time frame: Up to 5 years
Number of Participants With Progression Free Survival at 6 Months
Time frame: At 6 months
Number of Participants With Overall Survival at 6 Months
Time frame: At 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Apr 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 30825962Song A, Andrews DW, Werner-Wasik M, Kim L, Glass J, Bar-Ad V, Evans JJ, Farrell CJ, Judy KD, Daskalakis C, Zhan T, Shi W. Phase I trial of alisertib with concurrent fractionated stereotactic re-irradiation for recurrent high grade gliomas. Radiother Oncol. 2019 Mar;132:135-141. doi: 10.1016/j.radonc.2018.12.019. Epub 2019 Jan 4.
- Kimmel Cancer Center at Thomas Jefferson University, an NCI-Designated Cancer CenterLink provided by the sponsor.
- Thomas Jefferson University HospitalsLink provided by the sponsor.
Related trials for Adult Anaplastic Astrocytoma
RecruitingPhase 1/2
A Study of Zedoresertib (Debio 0123) in Combination With Temozolomide in Adult Participants With Recurrent or Progressive Glioblastoma and of Zedoresertib (Debio 0123) in Combination With Temozolomide and Radiotherapy in Adult Participants With Newly Diagnosed Glioblastoma
Glioblastoma IDH (Isocitrate Dehydrogenase) Wildtype, Astrocytoma, Grade III
RecruitingPhase 1
Phase I Study of Oral ONC206 in Recurrent and Rare Primary Central Nervous System Neoplasms
Central Nervous System Neoplasms, Glioblastoma
RecruitingPhase 1/2
A Study of Repotrectinib in Pediatric and Young Adult Subjects Harboring ALK, ROS1, OR NTRK1-3 Alterations
Locally Advanced Solid Tumors, Metastatic Solid Tumors
RecruitingObservational study
Targeted Pediatric High-Grade Glioma Therapy
High Grade Glioma, Diffuse Intrinsic Pontine Glioma
RecruitingPhase 2
Study of Olutasidenib and Temozolomide in HGG
High Grade Glioma, Astrocytoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Wenyin Shi, MD, PhD principal investigator
Thomas Jefferson University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Hyperfractionated radiation therapy, Stereotactic radiosurgery and Alisertib in people with Adult Anaplastic Astrocytoma and Adult Anaplastic Ependymoma, run by Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University at 1 site 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 16 inclusion and 12 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: finished, as of the sponsor's last update on 30 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Sep 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Tolerated Dose (MTD) of Alisertib (time frame: Up to 30 days after completion of radiation therapy). 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 NCT02186509, which also lists 1 linked publication.
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 30 Apr 2025.