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Recurrent GlioblastomaPhase 1NCT04854044

ONC201 and Radiation Therapy Before Surgery for the Treatment of Recurrent Glioblastoma

A Phase 1 study testing Akt/ERK Inhibitor ONC201, Radiation Therapy and Resection in people with Recurrent Glioblastoma and Recurrent Gliosarcoma, run by Jonsson Comprehensive Cancer Center at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

This phase I trial studies the effects of ONC201 in combination with standard of care radiation therapy in treating patients with glioblastoma that has come back (recurrent). ONC201 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Akt/ERK Inhibitor ONC201, Radiation Therapy and Resection
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteUnited States
Study dates
1 May 2021to 1 Jul 2026
Phase
Phase 1
Are there results?
None posted in the registry

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 proven glioblastoma or gliosarcoma which is progressive or recurrent following radiation therapy +/- chemotherapy
  • Participants must have evaluable, supratentorial contrast-enhancing progressive or recurrent glioblastoma or gliosarcoma by magnetic resonance imaging (MRI) imaging within 14 days of study treatment initiation. Participants must be able to tolerate MRIs
  • Participants can have any number of prior relapses
  • Participants must have recovered from severe toxicity of prior therapy. The following intervals from previous treatments are required to be eligible:
  • 12 weeks from the completion of radiation
  • 6 weeks from a nitrosourea chemotherapy or mitomycin C
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  • 23 days from temozolomide chemotherapy
  • 4-weeks from other cytotoxic therapy unless noted above
  • 4 weeks or 5-half-lives (whichever is shorter) from any other investigational (not Food and Drug Administration [FDA]-approved) agents (including vaccines)
  • Participants must be undergoing surgery that is clinically indicated as determined by their care providers. Patients must be eligible for surgical resection with the expectation that the surgeon is able to resect at least 300 mg of tumor with low risk of inducing neurological injury
  • Participants must be undergoing radiotherapy that is clinically indicated as determined by their care providers. The field of radiation must overlap the area of tumor planned for surgical resection. Participants must have a minimum tumor size of 2 x 2 cm^2 based on MRI scan prior to surgery
  • Participants must be 18 years of age or older
  • Participants must have a Karnofsky performance status >= 60% (i.e. the participant must be able to care for himself/herself with occasional help from others)
  • Absolute neutrophil count >= 1,500/mcL
  • Platelets >= 100,000/mcL
  • Hemoglobin >= 9 g/dL
  • Total bilirubin =< 1.5 x upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) / alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 2.5 x institutional upper limit of normal
  • Creatinine =< institutional upper limit of normal OR creatinine clearance >= 50 mL/min/1.73m^2 for patients with creatinine levels above institutional normal
  • Activated partial thromboplastin time/ partial thromboplastin time (APTT/PTT) =< 1.5 x institutional upper limit of normal (unless participant is receiving anticoagulant therapy as long as prothrombin time [PT] or aPTT is within therapeutic range of intended use of anticoagulants)
  • Female participants of childbearing potential must have a negative urine or serum pregnancy test prior to study entry. Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., age appropriate, history of vasomotor symptoms) or six months of spontaneous amenorrhea with serum follicle stimulating hormone [FSH] levels > 40 mIU/mL and estradiol < 20 pg/mL or have had surgical bilateral oophorectomy (with or without hysterectomy) at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential
  • Female participants of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and through 30 days after the last dose of study drug. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
  • Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and through 30 days after the last dose of study drug. Women who are nursing should discontinue nursing prior to starting study drug
  • Participants must have no concurrent malignancy except curatively treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix, breast, or bladder. Patients with prior malignancies must be disease-free for >= three years
  • Participants must be able to swallow whole capsules
  • Participants must have at least 20 (preferably 40) slides of archival tumor tissue from a prior surgery demonstrating GBM
  • Participants must have the ability to understand and the willingness to sign a written informed consent document

Who cannot join

  • Participants receiving any other investigational agents or using an investigational device are ineligible
  • Participants with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to ONC201 are ineligible
  • Participants may not have had prior treatment with ONC201
  • Participants may have had prior treatment with bevacizumab/VEGFR inhibitors, but last dose of treatment must be at least 4 weeks prior to the date of planned tumor resection
  • Participants may not be on concurrent treatment with Optune device. Prior use of the device is allowable
  • Participants must not have evidence of significant hematologic, renal, or hepatic dysfunction
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  • Participants with a history of any of the following within the last 6 months prior to study entry are ineligible:
  • Ischemic myocardial event, including angina requiring therapy and artery revascularization procedures
  • Ischemic cerebrovascular event, including transient ischemic attack (TIA) and artery revascularization procedures
  • Requirement for inotropic support (excluding digoxin) or serious (uncontrolled) cardiac arrhythmia (including atrial flutter/fibrillation, ventricular fibrillation or ventricular tachycardia)
  • Placement of a pacemaker for control of rhythm
  • New York Heart Association (NYHA) class III or IV heart failure
  • Participants with known significant active cardiovascular or pulmonary disease at the time of study entry are ineligible
  • Participants receiving therapeutic agents known to prolong QT interval will be excluded. Patients on sertraline which has the conditional risk of prolonging the QT interval will be allowed on study if they hold sertraline on the day of ONC201 administration
  • Participants using concomitant CYP3A4/5 inhibitors within 72 hours prior to starting study drug administration are ineligible
  • Participants with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements, are ineligible
  • Pregnant women are excluded from this study because there is unknown risk of ONC201 on the fetus. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother on ONC201, breastfeeding should be discontinued if the mother is treated with ONC201

Trial locations and contacts

1 site in 1 country.

United States1 site

  • UCLA / Jonsson Comprehensive Cancer Center

    Los Angeles, California, 90095

Other trials in United States

About this study

Official title: Phase 1b Study of ONC201 and Radiotherapy in Preoperative Recurrent Glioblastoma (GBM) Patients

This phase I trial studies the effects of ONC201 in combination with standard of care radiation therapy in treating patients with glioblastoma that has come back (recurrent). ONC201 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high energy photons to kill tumors cells and shrink tumors. Giving ONC201 in combination with radiation therapy may help treat patients with recurrent glioblastoma.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the safety and tolerability of Akt/ERK Inhibitor ONC201 (ONC201) in combination with radiotherapy before a tumor resection in recurrent glioblastoma (GBM) patients.

II. To determine the ability of ONC201 to decrease glioblastoma-initiating cells as determined by percentage of neurosphere formation of treated brain tumor tissues compared to non-treated brain tumor tissues.

SECONDARY OBJECTIVES:

  1. To determine the ability of ONC201 to decrease glioblastoma-initiating cells as determined by expression of glioma stem cells using ribonucleic acid-sequencing (RNA-Seq) of treated brain tumor tissues compared to non-treated brain tumor tissues.

II. To assess the ability of ONC201 to inhibit Akt by evaluating progressive disease (PD) markers by immunohistochemistry such as Sox2, Oct3/4, Nanog, Akt and p-Akt, GSK3 and pGSK3alpha.

EXPLORATORY OBJECTIVES:

  1. To estimate progression-free survival (PFS) and overall survival (OS). II. To determine the immunogenicity of the combination of ONC201 + radiation therapy (RT) via immune cell studies.

III. To determine if the combination of ONC201 + RT leads to increase cholesterol synthesis.

IV. To determine molecular markers of response to ONC201 in correlation to survival such as DRD5 expression.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients undergo radiation therapy for 10 fractions over 2 weeks, and receive ONC201 orally (PO) daily on days 1, 2, 8, and 9. Beginning 24 hours after completion of radiation therapy, patients undergo surgical resection. Beginning 7 days from last pre-surgery dose of ONC201, patients receive ONC201 PO daily on two consecutive days weekly (2 days on/5 days off) in the absence of disease progression or unacceptable toxicity.

ARM II: Patients undergo radiation therapy for 10 fractions over 2 weeks. Beginning 24 hours after completion of radiation therapy, patients undergo surgical resection. After recovery from surgery, patients receive ONC201 PO daily on two consecutive days weekly (2 days on/5 days off) in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and then every 3 months.

Being tested
Akt/ERK Inhibitor ONC201, Radiation Therapy, Resection
Medical subject headings
Glioblastoma, Gliosarcoma

What participants receive

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

  • Akt/ERK Inhibitor ONC201Drug

    Also called ONC201, TIC10

    Given orally

  • Radiation TherapyRadiation

    Also called Cancer Radiotherapy, ENERGY_TYPE, Irradiate, Irradiated

    Undergo radiation therapy

  • ResectionProcedure or surgery

    Also called Surgical Resection

    Undergo surgical resection

Study groups in NCT04854044
Study groupRoleWhat they receive
Arm I (ONC201, radiation therapy, resection)ExperimentalPatients undergo radiation therapy for 10 fractions over 2 weeks, and receive ONC201 PO daily on days 1, 2, 8, and 9. Beginning 24 hours after completion of radiation therapy, patients undergo surgical resection. Beginning 7 days from last pre-surgery dose of ONC201, patients receive ONC201 PO daily on two consecutive days weekly (2 days on/5 days off) in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Akt/ERK Inhibitor ONC201; Radiation: Radiation Therapy; Procedure: Resection
Arm II (ONC201, radiation therapy, resection)ExperimentalPatients undergo radiation therapy for 10 fractions over 2 weeks. Beginning 24 hours after completion of radiation therapy, patients undergo surgical resection. After recovery from surgery, patients receive ONC201 PO daily on two consecutive days weekly (2 days on/5 days off) in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Akt/ERK Inhibitor ONC201; Radiation: Radiation Therapy; Procedure: Resection

What is being measured

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

  1. Incidence of adverse events

    Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.

    Measured: Up to 90 days after the last study treatment

  2. Percentage of neurosphere formation

    A two-sample two-sided t-test will be performed to compare the percentage of neurosphere formation of treated brain tumor tissues and non-treated brain tumor tissues.

    Measured: At the tumor resection during surgery

Secondary outcomes (2)

  1. Expression of glioma stem cells using ribonucleic acid-sequencing (RNA-Seq)

    Will be compared between treated brain tumor tissues and non-treated brian tumor tissues. Markers for expression of glioma stem cells as determined by RNA-Seq and makers indicating cellular pathways leading to formation of GICs, such as Sox2, Oct3/4, Nanog, Akt and p-Akt, GSK3 and pGSK3alpha, will be examined graphically and summarized by descriptive statistics. Changes in markers pre- and post- treatment will be assessed using paired t-tests or Wilcoxon signed rank test. Between-group differences in these markers will be assessed by two-sample t-test or Wilcoxon rank-sum test for quantitative variables and by Chi-squared test or Fisher's exact test for categorical ones.

    Measured: At the tumor resection during surgery

  2. Pharmacodynamic (PD) markers

    Evaluated by immunohistochemistry such as Sox2, Oct3/4, Nanog, Akt and p-Akt, GSK3 and pGSK3alpha. Markers for expression of glioma stem cells as determined by RNA-Seq and makers indicating cellular pathways leading to formation of GICs, such as Sox2, Oct3/4, Nanog, Akt and p-Akt, GSK3 and pGSK3alpha, will be examined graphically and summarized by descriptive statistics. Changes in markers pre- and post- treatment will be assessed using paired t-tests or Wilcoxon signed rank test. Between-group differences in these markers will be assessed by two-sample t-test or Wilcoxon rank-sum test for quantitative variables and by Chi-squared test or Fisher's exact test for categorical ones.

    Measured: At the tumor resection during surgery

Timeline

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

  1. First posted22 Apr 2021
  2. Study start1 May 2021 (estimated)
  3. Primary completion1 Jul 2025 (estimated)
  4. Study completion1 Jul 2026 (estimated)

Why it stopped: The P.I. is not prepared to move forward at this thime

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 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04854044
Sponsor's protocol ID
21-000054
Other IDs
NCI-2021-02121, 21-000054, P50CA211015
Status last verified
Mar 2021
First submitted
31 Mar 2021
Last updated
12 May 2021
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Akt/ERK Inhibitor ONC201, Radiation Therapy and Resection in people with Recurrent Glioblastoma and Recurrent Gliosarcoma, run by Jonsson Comprehensive Cancer Center 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 27 inclusion and 17 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: withdrawn, as of the sponsor's last update on 12 May 2021. 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?

The study was withdrawn before enrolling participants, so there are no results.

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?

Incidence of adverse events (time frame: Up to 90 days after the last study treatment). The study lists 2 primary outcomes in all. 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 NCT04854044.

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 12 May 2021.

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