A Phase 1/2 interventional study of Zotiraciclib (TG02) and Temozolomide (TMZ) in Brain Tumor, Astrocytoma and Astroglioma, sponsored by National Cancer Institute (NCI). Terminated at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-02-23.
Sponsored by National Cancer Institute (NCI) · Phase 1/2, Interventional, and Treatment
Background:
Zotiraciclib (TG02) is an investigational drug that penetrates the blood-brain barrier and might treat brain tumors. Temozolomide (TMZ) is a drug used to treat brain tumors.
Objective:
To find out if Zotiraciclib (TG02) is safe, and to find out if it in combination with TMZ is as effective as TMZ alone in people with brain tumors.
Eligibility:
People ages 18 and older with a brain tumor that has progressed after standard treatment
Design:
In phase I part, the Bayesian optimal interval (BOIN) design will be used to find the maximum tolerated dose (MTD) of Zotiraciclib (TG02) for Arm 1 (dose dense TMZ) and Arm 2 (metronomic TMZ) independently. Then a randomized cohort expansion compared progression free survival at 4 months (PFS4) of the two arms for an efficient determination of a TMZ schedule to combine with Zotiraciclib at MTD.
In Phase II part, a Bayesian design based on posterior probability will be used to monitor efficacy.
Participants will be screened with:
Participants will take Zotiraciclib (TG02) plus TMZ by mouth in 28-day cycles.
Participants will have study visits. These include:
Participants will continue treatment until their disease gets worse or they have intolerable side effects.
Participants will also be enrolled in another protocol to test molecular markers for their brain tumor.
Background:
Objectives:
Phase I:
-To determine the maximum tolerated dose (MTD) of Zotiraciclib (TG02) plus TMZ using both the dd and mn TMZ schedules in adult patients with recurrent anaplastic astrocytoma or glioblastoma/gliosarcoma.
To select the treatment regimen with better progression free survival (PFS)4 between Zotiraciclib (TG02) plus dd TMZ or mn TMZ at each of the MTDs following cohort expansion.
Phase II:
-To determine the efficacy of Zotiraciclib (TG02) plus TMZ versus TMZ alone in patients with recurrent World Health Organization (WHO) grade III or IV astrocytoma as determined by progression free survival.
Eligibility:
Design:
Phase I:
Phase II:
--Patients will be randomized between two competing treatment arms: ("winner" of dd vs mn) TMZ + Zotiraciclib (TG02) versus dd/mn TMZ alone using a Bayesian clinical trial design. The dosage for the combination arm will be derived from the MTD determined in the Phase I component of the study.
2,440 studies on the registry are indexed under Brain Neoplasms; 540 are open to participants now.
This study's enrollment of 53 is above the median of 40 across 1,831 interventional studies indexed under Brain Neoplasms.
Browse Brain Neoplasms studies →National Cancer Institute (NCI) is the lead sponsor of 3,556 studies on the registry; 336 are open to participants now.
Of its 411 completed or terminated interventional studies of FDA-regulated products, 373 (91%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
At the time of registration, subject must be removed from prior therapy as follows:
Patients having undergone recent resection of recurrent or progressive tumor will be eligible given all of the following conditions apply:
EXCLUSION CRITERIA:
Any condition, including the presence of laboratory abnormalities, which places the patient at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study. These would include:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Neoadjuvant treatment is given before the main treatment (usually surgery), often to shrink a tumour. Adjuvant treatment is given after it, to lower the chance of the cancer coming back.
A 0–100 scale of how well someone can carry out everyday activities. 100 is no complaints and no signs of illness; 70 is able to look after yourself but not to work or keep up normal activity; 50 is needing considerable help and frequent medical care.
Studies often ask for 60 or 70 and above. Your doctor gives the score.
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
Histologically or cytologically confirmed
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Biopsy and archival tissue
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Adjuvant and neoadjuvant
Neoadjuvant treatment is given before the main treatment (usually surgery), often to shrink a tumour. Adjuvant treatment is given after it, to lower the chance of the cancer coming back.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Karnofsky performance status (KPS)
A 0–100 scale of how well someone can carry out everyday activities. 100 is no complaints and no signs of illness; 70 is able to look after yourself but not to work or keep up normal activity; 50 is needing considerable help and frequent medical care.
Studies often ask for 60 or 70 and above. Your doctor gives the score.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Absolute neutrophil count (ANC)
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Relapsed and refractory
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis C tests
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
CYP3A (CYP3A4) inhibitors and inducers
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
QT and QTc
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
dose dense (dd) Temozolomide (TMZ) 125 mg/m\^2 x 7 days on / 7 days off plus Zotiraciclib (TG02) dose escalation
Drug: Zotiraciclib (TG02) · Drug: Temozolomide (TMZ)
metronomic Temozolomide (TMZ) 50 mg/ m\^2 daily plus Zotiraciclib (TG02) dose escalation
Drug: Zotiraciclib (TG02) · Drug: Temozolomide (TMZ)
Maximum tolerated dose (MTD) of Zotiraciclib (TG02) from phase I plus and "winner" of dose dense (dd) vs metronomic Temozolomide (TMZ) from phase I
Drug: Zotiraciclib (TG02) · Drug: Temozolomide (TMZ)
"winner" of dose dense (dd) vs metronomic Temozolomide (TMZ) from phase I alone
Drug: Temozolomide (TMZ)
Phase I: Two treatment arms and several dose levels are planned; In the maximum tolerated dose (MTD) finding part, Temozolomide (TMZ) with two alternate schedules (dose dense (dd) and metronomic (mn) in combination with Zotiraciclib (TG02) will be administered; --A cohort extension of both arms will be performed at each MTD and the treatment arm with a better progression free survival at 4 months (PFS4) will be selected for the combination treatment arm for Phase II; Patients will be randomized between two competing treatment arms: (winner of dd vs mn) TMZ + Zotiraciclib (TG02) versus dd/mn TMZ alone using a Bayesian clinical trial design. The dosage for the combination arm will be derived from the MTD determined in the Phase I component of the study.
Also known as: TG02
Phase I: In the maximum tolerated dose (MTD) finding part, Temozolomide (TMZ) with two alternate schedules (dose dense (dd) and metronomic (mn) in combination with Zotiraciclib (TG02) will be administered; A cohort extension of both arms will be performed at each MTD and the treatment arm with a better progression free survival at 4 months (PFS4) will be selected for the combination treatment arm for Phase II; Patients will be randomized between two competing treatment arms: ("winner" of dd vs mn) TMZ + Zotiraciclib (TG02) versus dd/mn TMZ alone using a Bayesian clinical trial design.
Also known as: Temodar
Phase I: Maximum Tolerated Dose (MTD) of Zotiraciclib in Combination With Dose Dense (dd) Temozolomide (TMZ) in Adult Patients With Recurrent Anaplastic Astrocytoma or Glioblastoma/Gliosarcoma
Maximum tolerated dose of Zotiraciclib (TG02) in combination with dose dense Temozolomide (TMZ) was assessed using the Bayesian Optimal Interval (BOIN) design. The MTD is defined as the dose for which the isotonic estimate of the toxicity rate is closest to the target toxicity rate of 0.35. If there are ties, we select the higher dose level when the isotonic estimate is lower than the target toxicity rate; and we select the lower dose level when the isotonic estimate is greater than the target toxicity rate of 0.35.
Time frame: 4 weeks after initiation of treatment
Phase I: Maximum Tolerated Dose (MTD) of Zotiraciclib (TG02) in Combination of Metronomic (mn) Temozolomide (TMZ) in Adult Patients With Recurrent Anaplastic Astrocytoma or Glioblastoma/Gliosarcoma
Maximum tolerated dose of metronomic (mn) Zotiraciclib (TG02) was assessed using the Bayesian Optimal Interval (BOIN) design. The MTD is defined as the dose for which the isotonic estimate of the toxicity rate is closest to the target toxicity rate of 0.35. If there are ties, we select the higher dose level when the isotonic estimate is lower than the target toxicity rate; and we select the lower dose level when the isotonic estimate is greater than the target toxicity rate of 0.35.
Time frame: 4 weeks after initiation of treatment
% of Participants Free of Disease Progression at 4mos Treated w/Zotiraciclib at the Maximum Tolerated Dose in Combination Temozolomide w/Dose Dense Temozolomide Schedules in Adult Patients With Recurrent Anaplastic Astrocytoma or Glioblastoma/Gliosarcoma
We first determined the maximum tolerated dose (MTDs) in each ARM and we then performed the cohort expansion at the MTD in both ARMs separately, until we treated a total of 18 participants at this dose in each ARM. PFS is defined as the duration of time from start of registration to time of progression or death, whichever comes first. Progression was assessed by the Response Assessment in Neuro-Oncology Criteria (RANO). Progression is ≥25% increase in tumor volume compared to baseline in the sum of the products of perpendicular diameters of enhancing lesions compared with the smallest measurement obtained either at baseline or best response with the participant on stable or increasing doses of steroids. Significant increase in T2-weighted-Fluid-Attenuated Inversion Recovery (T2/FLAIR) non-enhancing lesions with the participant on stable or increasing doses of steroids (not caused by comorbid events). Any new lesions.
Time frame: 4 months
% of Participants Free of Disease Progression at 4mos Treated w/Zotiraciclib at the Maximum Tolerated Dose (MTD) in Combination With the Metronomic (mn) Temozolomide (TMZ) in Adult Patients With Recurrent Anaplastic Astrocytoma or Glioblastoma/Gliosarcoma
We first determined the MTDs in each ARM and we then performed the cohort expansion at the MTD in both ARMs separately, until we treated a total of 18 participants at this dose in each ARM. PFS is defined as the duration of time from start of registration to time of progression or death, whichever comes first. Progression was assessed by the Response Assessment in Neuro-Oncology Criteria (RANO). Progression is ≥25% increase in tumor volume compared to baseline in the sum of the products of perpendicular diameters of enhancing lesions compared with the smallest measurement obtained either at baseline or best response with the participant on stable or increasing doses of steroids. Significant increase in T2-weighted-Fluid-Attenuated Inversion Recovery (T2/FLAIR) non-enhancing lesions with the participant on stable or increasing doses of steroids (not caused by comorbid events). Any new lesions.
Time frame: 4 months
Phase II: Progression Free Survival in Subjects Taking Zotiraciclib (TG02) Plus Temozolomide (TMZ) Versus TMZ Alone in Patients With Recurrent World Health Organization (WHO) Grade III or IV Astrocytoma.
Median amount of time subject survives without disease progression after treatment
Time frame: Disease progression
Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0)
Here is the number of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
Time frame: Date treatment consent signed to date off study, approximately 15mo(m)/8days(d), 26m, 7m/26d, 13m/17d, 11m/30d, 12m/6d, 19m/11d, 9m/28d and 18m/21d for Group 1-9 respectively.
Phase I: Number of Participants With a Dose-limiting Toxicity (DLT)
DLT is defined as any adverse events attributed to the study drug. For example, Grade 4 neutropenia lasting 5 days or more. Febrile neutropenia defined as grade 3-4 neutropenia with fever ≥38.5ºC and/or infection requiring antibiotic or antifungal treatment. Nausea or vomiting that responds to symptomatic therapy and lasts ≤7 days. Fatigue that responds to symptomatic therapy and lasts ≤7 days. And weight gain (in patients on steroids).
Time frame: 4 weeks after initiation of treatment
| Milestone | ARM 1 Dose Level 0 - (Starting Dose) | ARM 1 Dose Level 1 - (Dose Escalation) | ARM 2 Dose Level 0 (Starting Dose) | ARM 2 Dose 1 - (Dose Escalation) | ARM 2 Dose 0 - (Dose De-escalation) | ARM 2 Dose Level II - (Dose Escalation) | ARM 2 Dose Level I - (Dose De-escalation) | ARM 1 Dose Level 1 (MTD Level in ARM1) | ARM 2 Dose Level 1 (MTD Level in ARM2) |
|---|---|---|---|---|---|---|---|---|---|
| Started | 6 | 13 | 3 | 6 | 3 | 2 | 7 | 0 | 0 |
| Completed | 6 | 12 | 3 | 6 | 3 | 2 | 6 | 0 | 0 |
| Not completed | 0 | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Withdrew: Withdrawal of consent | 0 | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Milestone | ARM 1 Dose Level 0 - (Starting Dose) | ARM 1 Dose Level 1 - (Dose Escalation) | ARM 2 Dose Level 0 (Starting Dose) | ARM 2 Dose 1 - (Dose Escalation) | ARM 2 Dose 0 - (Dose De-escalation) | ARM 2 Dose Level II - (Dose Escalation) | ARM 2 Dose Level I - (Dose De-escalation) | ARM 1 Dose Level 1 (MTD Level in ARM1) | ARM 2 Dose Level 1 (MTD Level in ARM2) |
|---|---|---|---|---|---|---|---|---|---|
| Started | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 6 | 7 |
| Completed | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 6 | 6 |
| Not completed | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Withdrew: Withdrawal of consent | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
Maximum tolerated dose of Zotiraciclib (TG02) in combination with dose dense Temozolomide (TMZ) was assessed using the Bayesian Optimal Interval (BOIN) design. The MTD is defined as the dose for which the isotonic estimate of the toxicity rate is closest to the target toxicity rate of 0.35. If there are ties, we select the higher dose level when the isotonic estimate is lower than the target toxicity rate; and we select the lower dose level when the isotonic estimate is greater than the target toxicity rate of 0.35.
| mg/day | All Participants |
|---|---|
| Phase I: Maximum Tolerated Dose (MTD) of Zotiraciclib in Combination With Dose Dense (dd) Temozolomide (TMZ) in Adult Patients With Recurrent Anaplastic Astrocytoma or Glioblastoma/Gliosarcoma | 250 |
Maximum tolerated dose of metronomic (mn) Zotiraciclib (TG02) was assessed using the Bayesian Optimal Interval (BOIN) design. The MTD is defined as the dose for which the isotonic estimate of the toxicity rate is closest to the target toxicity rate of 0.35. If there are ties, we select the higher dose level when the isotonic estimate is lower than the target toxicity rate; and we select the lower dose level when the isotonic estimate is greater than the target toxicity rate of 0.35.
| mg/day | All Participants |
|---|---|
| Phase I: Maximum Tolerated Dose (MTD) of Zotiraciclib (TG02) in Combination of Metronomic (mn) Temozolomide (TMZ) in Adult Patients With Recurrent Anaplastic Astrocytoma or Glioblastoma/Gliosarcoma | 250 |
We first determined the maximum tolerated dose (MTDs) in each ARM and we then performed the cohort expansion at the MTD in both ARMs separately, until we treated a total of 18 participants at this dose in each ARM. PFS is defined as the duration of time from start of registration to time of progression or death, whichever comes first. Progression was assessed by the Response Assessment in Neuro-Oncology Criteria (RANO). Progression is ≥25% increase in tumor volume compared to baseline in the sum of the products of perpendicular diameters of enhancing lesions compared with the smallest measurement obtained either at baseline or best response with the participant on stable or increasing doses of steroids. Significant increase in T2-weighted-Fluid-Attenuated Inversion Recovery (T2/FLAIR) non-enhancing lesions with the participant on stable or increasing doses of steroids (not caused by comorbid events). Any new lesions.
| percentage of participants | All Participants |
|---|---|
| % of Participants Free of Disease Progression at 4mos Treated w/Zotiraciclib at the Maximum Tolerated Dose in Combination Temozolomide w/Dose Dense Temozolomide Schedules in Adult Patients With Recurrent Anaplastic Astrocytoma or Glioblastoma/Gliosarcoma | 40 |
We first determined the MTDs in each ARM and we then performed the cohort expansion at the MTD in both ARMs separately, until we treated a total of 18 participants at this dose in each ARM. PFS is defined as the duration of time from start of registration to time of progression or death, whichever comes first. Progression was assessed by the Response Assessment in Neuro-Oncology Criteria (RANO). Progression is ≥25% increase in tumor volume compared to baseline in the sum of the products of perpendicular diameters of enhancing lesions compared with the smallest measurement obtained either at baseline or best response with the participant on stable or increasing doses of steroids. Significant increase in T2-weighted-Fluid-Attenuated Inversion Recovery (T2/FLAIR) non-enhancing lesions with the participant on stable or increasing doses of steroids (not caused by comorbid events). Any new lesions.
| percentage of participants | All Participants |
|---|---|
| % of Participants Free of Disease Progression at 4mos Treated w/Zotiraciclib at the Maximum Tolerated Dose (MTD) in Combination With the Metronomic (mn) Temozolomide (TMZ) in Adult Patients With Recurrent Anaplastic Astrocytoma or Glioblastoma/Gliosarcoma | 25 |
Median amount of time subject survives without disease progression after treatment
No measurements were reported for this outcome.
Here is the number of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
| Participants | ARM 1 Dose Level 0 - (Starting Dose) | ARM 1 Dose Level 1 - (Dose Escalation) | ARM 2 Dose Level 0 (Starting Dose) | ARM 2 Dose 1 - (Dose Escalation) | ARM 2 Dose 0 - (Dose De-escalation) | ARM 2 Dose Level II - (Dose Escalation) | ARM 2 Dose Level I - (Dose De-escalation) | ARM 1 Dose Level 1 (MTD Level in ARM1) | ARM 2 Dose Level 1 (MTD Level in ARM2) |
|---|---|---|---|---|---|---|---|---|---|
| Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0) | 6 | 13 | 3 | 6 | 3 | 2 | 7 | 6 | 7 |
DLT is defined as any adverse events attributed to the study drug. For example, Grade 4 neutropenia lasting 5 days or more. Febrile neutropenia defined as grade 3-4 neutropenia with fever ≥38.5ºC and/or infection requiring antibiotic or antifungal treatment. Nausea or vomiting that responds to symptomatic therapy and lasts ≤7 days. Fatigue that responds to symptomatic therapy and lasts ≤7 days. And weight gain (in patients on steroids).
| Participants | ARM 1 Dose Level 0 - (Starting Dose) | ARM 1 Dose Level 1 - (Dose Escalation) | ARM 2 Dose Level 0 (Starting Dose) | ARM 2 Dose 1 - (Dose Escalation) | ARM 2 Dose 0 - (Dose De-escalation) | ARM 2 Dose Level II - (Dose Escalation) | ARM 2 Dose Level I - (Dose De-escalation) | ARM 1 Dose Level 1 (MTD Level in ARM1) | ARM 2 Dose Level 1 (MTD Level in ARM2) |
|---|---|---|---|---|---|---|---|---|---|
| Phase I: Number of Participants With a Dose-limiting Toxicity (DLT) | 1 | 3 | 0 | 3 | 1 | 1 | 4 | — | — |
Collected over Date treatment consent signed to date off study, approximately 15mo(m)/8days(d), 26m, 7m/26d, 13m/17d, 11m/30d, 12m/6d, 19m/11d, 9m/28d and 18m/21d for Group 1-9 respectively.. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| ARM 1 Dose Level 0 (Starting Dose) | 0/6 (0%) | 3/6 (50%) | 6/6 (100%) |
| ARM 1 Dose Level 1 (Dose Escalation) | 0/13 (0%) | 8/13 (61.5%) | 13/13 (100%) |
| ARM 2 Dose Level 0 (Starting Dose) | 2/3 (66.7%) | 1/3 (33.3%) | 3/3 (100%) |
| ARM 2 Dose 1 (Dose Escalation) | 0/6 (0%) | 4/6 (66.7%) | 6/6 (100%) |
| ARM 2 Dose 0 (Dose De-escalation) | 1/3 (33.3%) | 1/3 (33.3%) | 3/3 (100%) |
| ARM 2 Dose Level II (Dose Escalation) | 0/2 (0%) | 2/2 (100%) | 2/2 (100%) |
| ARM 2 Dose Level I (Dose De-escalation) | 1/7 (14.3%) | 2/7 (28.6%) | 7/7 (100%) |
| ARM 1 Dose Level 1 (MTD Level in ARM1) | 0/6 (0%) | 2/6 (33.3%) | 6/6 (100%) |
| ARM 2 Dose Level 1 (MTD Level in ARM2) | 0/7 (0%) | 2/7 (28.6%) | 7/7 (100%) |
| Event | ARM 1 Dose Level 0 (Starting Dose) | ARM 1 Dose Level 1 (Dose Escalation) | ARM 2 Dose Level 0 (Starting Dose) | ARM 2 Dose 1 (Dose Escalation) | ARM 2 Dose 0 (Dose De-escalation) | ARM 2 Dose Level II (Dose Escalation) | ARM 2 Dose Level I (Dose De-escalation) | ARM 1 Dose Level 1 (MTD Level in ARM1) | ARM 2 Dose Level 1 (MTD Level in ARM2) |
|---|---|---|---|---|---|---|---|---|---|
| Alanine aminotransferase increasedInvestigations | 0/6 | 0/13 | 0/3 | 0/6 | 0/3 | 1/2 | 0/7 | 0/6 | 0/7 |
| EncephalopathyNervous system disorders | 0/6 | 0/13 | 0/3 | 0/6 | 0/3 | 1/2 | 0/7 | 1/6 | 0/7 |
| Febrile neutropeniaBlood and lymphatic system disorders | 0/6 | 0/13 | 0/3 | 0/6 | 0/3 | 1/2 | 0/7 | 0/6 | 0/7 |
| SeizureNervous system disorders | 0/6 | 2/13 | 0/3 | 0/6 | 1/3 | 1/2 | 0/7 | 1/6 | 0/7 |
| ConfusionPsychiatric disorders | 0/6 | 0/13 | 1/3 | 0/6 | 1/3 | 0/2 | 0/7 | 0/6 | 0/7 |
| Edema cerebralNervous system disorders | 0/6 | 1/13 | 0/3 | 0/6 | 1/3 | 0/2 | 0/7 | 0/6 | 0/7 |
| Neutrophil count decreasedInvestigations | 2/6 | 0/13 | 1/3 | 0/6 | 1/3 | 0/2 | 0/7 | 0/6 | 0/7 |
| White blood cell decreasedInvestigations | 2/6 | 0/13 | 1/3 | 0/6 | 0/3 | 0/2 | 0/7 | 0/6 | 0/7 |
| FatigueGeneral disorders | 0/6 | 0/13 | 0/3 | 0/6 | 0/3 | 0/2 | 2/7 | 0/6 | 0/7 |
| Intracranial hemorrhageNervous system disorders | 0/6 | 3/13 | 0/3 | 0/6 | 0/3 | 0/2 | 0/7 | 0/6 | 0/7 |
| Event | ARM 1 Dose Level 0 (Starting Dose) | ARM 1 Dose Level 1 (Dose Escalation) | ARM 2 Dose Level 0 (Starting Dose) | ARM 2 Dose 1 (Dose Escalation) | ARM 2 Dose 0 (Dose De-escalation) | ARM 2 Dose Level II (Dose Escalation) | ARM 2 Dose Level I (Dose De-escalation) | ARM 1 Dose Level 1 (MTD Level in ARM1) | ARM 2 Dose Level 1 (MTD Level in ARM2) |
|---|---|---|---|---|---|---|---|---|---|
| Alanine aminotransferase increasedInvestigations | 4/6 | 11/13 | 1/3 | 6/6 | 2/3 | 1/2 | 3/7 | 4/6 | 6/7 |
| Aspartate aminotransferase increasedInvestigations | 2/6 | 8/13 | 1/3 | 4/6 | 1/3 | 2/2 | 3/7 | 2/6 | 5/7 |
| ConstipationGastrointestinal disorders | 3/6 | 5/13 | 3/3 | 0/6 | 1/3 | 1/2 | 1/7 | 2/6 | 1/7 |
| DiarrheaGastrointestinal disorders | 5/6 | 9/13 | 3/3 | 2/6 | 1/3 | 1/2 | 4/7 | 2/6 | 6/7 |
| FatigueGeneral disorders | 4/6 | 7/13 | 3/3 | 5/6 | 1/3 | 1/2 | 5/7 | 3/6 | 5/7 |
| Lymphocyte count decreasedInvestigations | 6/6 | 9/13 | 3/3 | 6/6 | 0/3 | 2/2 | 5/7 | 6/6 | 7/7 |
| NauseaGastrointestinal disorders | 4/6 | 7/13 | 2/3 | 4/6 | 3/3 | 1/2 | 5/7 | 1/6 | 6/7 |
| Neutrophil count decreasedInvestigations | 4/6 | 7/13 | 2/3 | 3/6 | 1/3 | 1/2 | 4/7 | 5/6 | 7/7 |
| Platelet count decreasedInvestigations | 4/6 | 10/13 | 0/3 | 6/6 | 1/3 | 1/2 | 2/7 | 4/6 | 4/7 |
| VomitingGastrointestinal disorders | 4/6 | 3/13 | 1/3 | 4/6 | 1/3 | 2/2 | 5/7 | 1/6 | 3/7 |
| Age, Categorical(Participants) | ARM 1 Dose Level 0 - (Starting Dose) | ARM 1 Dose Level 1 - (Dose Escalation) | ARM 2 Dose Level 0 (Starting Dose) | ARM 2 Dose 1 - (Dose Escalation) | ARM 2 Dose 0 - (Dose De-escalation) | ARM 2 Dose Level II - (Dose Escalation) | ARM 2 Dose Level I - (Dose De-escalation) | ARM 1 Dose Level 1 (MTD Level in ARM1) | ARM 2 Dose Level 1 (MTD Level in ARM2) | Total |
|---|---|---|---|---|---|---|---|---|---|---|
| <=18 years | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Between 18 and 65 years | 5 | 13 | 3 | 5 | 3 | 2 | 6 | 4 | 5 | 46 |
| >=65 years | 1 | 0 | 0 | 1 | 0 | 0 | 1 | 2 | 2 | 7 |
| Age, Continuous(years) | ARM 1 Dose Level 0 - (Starting Dose) | ARM 1 Dose Level 1 - (Dose Escalation) | ARM 2 Dose Level 0 (Starting Dose) | ARM 2 Dose 1 - (Dose Escalation) | ARM 2 Dose 0 - (Dose De-escalation) | ARM 2 Dose Level II - (Dose Escalation) | ARM 2 Dose Level I - (Dose De-escalation) | ARM 1 Dose Level 1 (MTD Level in ARM1) | ARM 2 Dose Level 1 (MTD Level in ARM2) | Total |
|---|---|---|---|---|---|---|---|---|---|---|
| Mean | 49.47 ± 18.41 | 48.15 ± 10.47 | 33.3 ± 12.93 | 55.2 ± 14.25 | 38.7 ± 18.68 | 49.05 ± 11.1 | 54.46 ± 9.87 | 56.38 ± 11.63 | 56.36 ± 13.15 | 50.38 ± 12.49 |
| Sex: Female, Male(Participants) | ARM 1 Dose Level 0 - (Starting Dose) | ARM 1 Dose Level 1 - (Dose Escalation) | ARM 2 Dose Level 0 (Starting Dose) | ARM 2 Dose 1 - (Dose Escalation) | ARM 2 Dose 0 - (Dose De-escalation) | ARM 2 Dose Level II - (Dose Escalation) | ARM 2 Dose Level I - (Dose De-escalation) | ARM 1 Dose Level 1 (MTD Level in ARM1) | ARM 2 Dose Level 1 (MTD Level in ARM2) | Total |
|---|---|---|---|---|---|---|---|---|---|---|
| Female | 2 | 4 | 0 | 0 | 1 | 1 | 4 | 0 | 1 | 13 |
| Male | 4 | 9 | 3 | 6 | 2 | 1 | 3 | 6 | 6 | 40 |
| Ethnicity (NIH/OMB)(Participants) | ARM 1 Dose Level 0 - (Starting Dose) | ARM 1 Dose Level 1 - (Dose Escalation) | ARM 2 Dose Level 0 (Starting Dose) | ARM 2 Dose 1 - (Dose Escalation) | ARM 2 Dose 0 - (Dose De-escalation) | ARM 2 Dose Level II - (Dose Escalation) | ARM 2 Dose Level I - (Dose De-escalation) | ARM 1 Dose Level 1 (MTD Level in ARM1) | ARM 2 Dose Level 1 (MTD Level in ARM2) | Total |
|---|---|---|---|---|---|---|---|---|---|---|
| Hispanic or Latino | 1 | 0 | 0 | 1 | 1 | 0 | 0 | 1 | 0 | 4 |
| Not Hispanic or Latino | 5 | 12 | 3 | 5 | 2 | 2 | 7 | 5 | 7 | 48 |
| Unknown or Not Reported | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Race (NIH/OMB)(Participants) | ARM 1 Dose Level 0 - (Starting Dose) | ARM 1 Dose Level 1 - (Dose Escalation) | ARM 2 Dose Level 0 (Starting Dose) | ARM 2 Dose 1 - (Dose Escalation) | ARM 2 Dose 0 - (Dose De-escalation) | ARM 2 Dose Level II - (Dose Escalation) | ARM 2 Dose Level I - (Dose De-escalation) | ARM 1 Dose Level 1 (MTD Level in ARM1) | ARM 2 Dose Level 1 (MTD Level in ARM2) | Total |
|---|---|---|---|---|---|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Black or African American | 0 | 0 | 0 | 0 | 1 | 0 | 2 | 1 | 0 | 4 |
| White | 6 | 12 | 3 | 5 | 1 | 2 | 5 | 4 | 7 | 45 |
| More than one race | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 1 | 0 | 3 |
| Region of Enrollment(participants) | ARM 1 Dose Level 0 - (Starting Dose) | ARM 1 Dose Level 1 - (Dose Escalation) | ARM 2 Dose Level 0 (Starting Dose) | ARM 2 Dose 1 - (Dose Escalation) | ARM 2 Dose 0 - (Dose De-escalation) | ARM 2 Dose Level II - (Dose Escalation) | ARM 2 Dose Level I - (Dose De-escalation) | ARM 1 Dose Level 1 (MTD Level in ARM1) | ARM 2 Dose Level 1 (MTD Level in ARM2) | Total |
|---|---|---|---|---|---|---|---|---|---|---|
| United States | 6 | 13 | 3 | 6 | 3 | 2 | 7 | 6 | 7 | 53 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: Yes — We plan to share the Study Protocol, SAP and the Informed Consent Form on ClinicalTrials.gov.
Supporting information: Study protocol, Statistical analysis plan, Informed consent form
Time frame: Study Protocol, SAP, and Informed Consent Form will be available indefinitely after summary results data is published on clinicaltrials.gov.
Access criteria: Study Protocol, SAP, and Informed Consent Form will be accessible via clinicaltrials.gov.
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Studies of the drug tested here: Zotiraciclib
National Cancer Institute (NCI) →