Trial · NCT02942264

Zotiraciclib (TG02) Plus Dose-Dense or Metronomic Temozolomide Followed by Randomized Phase II Trial of Zotiraciclib (TG02) Plus Temozolomide Versus Temozolomide Alone in Adults With Recurrent Anaplastic Astrocytoma and Glioblastoma

NCT02942264, Phase 1, Phase 2, Terminated, National Cancer Institute (NCI); results first posted 2021-09-28

3 sourcestrials-2026-11-12-0.5.0

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ConductScience Library. Zotiraciclib (TG02) Plus Dose-Dense or Metronomic Temozolomide Followed by Randomized Phase II Trial of Zotiraciclib (TG02) Plus Temozolomide Versus Temozolomide Alone in Adults With Recurrent Anaplastic Astrocytoma and Glioblastoma. Trials, record NCT02942264. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT02942264

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Trial

As registered on ClinicalTrials.gov, in the graph's capture of the registry.

Title: Zotiraciclib (TG02) Plus Dose-Dense or Metronomic Temozolomide Followed by Randomized Phase II Trial of Zotiraciclib (TG02) Plus Temozolomide Versus Temozolomide Alone in Adults With Recurrent Anaplastic Astrocytoma and Glioblastoma
NCT number: NCT02942264
Status: Terminated
Phases: Phase 1, Phase 2
Enrollment: 53 participants, actual
Lead sponsor: National Cancer Institute (NCI)
Conditions: Brain Tumor, Astrocytoma, Astroglioma, Glioblastoma, Gliosarcoma
Interventions: Zotiraciclib (TG02), Temozolomide (TMZ)
First posted: 2016-10-24
Last updated: 2026-02-23
Results first posted: 2021-09-28

Source ClinicalTrials.gov

Registered outcomes7

Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.

List	Outcome	Time frame	Description
Primary	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	4 weeks after initiation of treatment	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.
Primary	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	4 weeks after initiation of treatment	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.
Primary	% 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	4 months	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.
Primary	% 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	4 months	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.
Primary	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.	Disease progression	Median amount of time subject survives without disease progression after treatment
Other	Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0)	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.	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.
Other	Phase I: Number of Participants With a Dose-limiting Toxicity (DLT)	4 weeks after initiation of treatment	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).

Source ClinicalTrials.gov

Outcomes7

Each outcome the trial posted results for, in ClinicalTrials.gov's words.

Type	Outcome	Time frame	Population	Units	Measured as
PRIMARY	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	4 weeks after initiation of treatment		mg/day	NUMBER
PRIMARY	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	4 weeks after initiation of treatment		mg/day	NUMBER
PRIMARY	% 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	4 months		percentage of participants	NUMBER
PRIMARY	% 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	4 months		percentage of participants	NUMBER
PRIMARY	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.	Disease progression	This outcome measure was not done because a Phase II study and strategy will be discussed in an upcoming meeting with the FDA to potentially conduct the Phase II as a separate protocol.	mg/day	NUMBER
OTHER_PRE_SPECIFIED	Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0)	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.		Participants	COUNT_OF_PARTICIPANTS
OTHER_PRE_SPECIFIED	Phase I: Number of Participants With a Dose-limiting Toxicity (DLT)	4 weeks after initiation of treatment	Arm2 DI: After prot. amend. previously defined gr 4 lymphopenia was no longer counted as DLT. 2/3 DLTs listed here are no longer DLTs. Arm2 D0:Prot. amend occurred after this dose de-escal. Re-eval. of DLT rate at DL1 led to the next dose escal. Analysis not applic. for Arm1 DL1\& Arm2D. Arm1 DL1:Per study design, pts in expans. stage are not analyzed for DLT. Arm2 DL1:Per study design, pts in expans. stage are not analyzed for DLT;as part of the expans. no pt in this grp were analyzed for DLT.	Participants	COUNT_OF_PARTICIPANTS

Source ClinicalTrials.gov

Results by group20

Each measurement the trial posted, group by group, in the words and numbers it posted.

Outcome	Group	Value	Units
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	All Participants	250	mg/day
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	All Participants	250	mg/day
% 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	All Participants	40	percentage of 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	All Participants	25	percentage of participants
Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0)	ARM 1 Dose Level 0 - (Starting Dose)	6	Participants
Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0)	ARM 1 Dose Level 1 - (Dose Escalation)	13	Participants
Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0)	ARM 2 Dose Level 0 (Starting Dose)	3	Participants
Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0)	ARM 2 Dose 1 - (Dose Escalation)	6	Participants
Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0)	ARM 2 Dose 0 - (Dose De-escalation)	3	Participants
Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0)	ARM 2 Dose Level II - (Dose Escalation)	2	Participants

1 to 10 of 20Source ClinicalTrials.gov

See all 20 results by group

Participant flow54

How many started, completed or left each group, period by period.

Period	Milestone	Group	Participants
Phase 1 MTD finding Stage	STARTED	ARM 1 Dose Level 0 - (Starting Dose)	6
Phase 1 MTD finding Stage	STARTED	ARM 1 Dose Level 1 - (Dose Escalation)	13
Phase 1 MTD finding Stage	STARTED	ARM 2 Dose Level 0 (Starting Dose)	3
Phase 1 MTD finding Stage	STARTED	ARM 2 Dose 1 - (Dose Escalation)	6
Phase 1 MTD finding Stage	STARTED	ARM 2 Dose 0 - (Dose De-escalation)	3
Phase 1 MTD finding Stage	STARTED	ARM 2 Dose Level II - (Dose Escalation)	2
Phase 1 MTD finding Stage	STARTED	ARM 2 Dose Level I - (Dose De-escalation)	7
Phase 1 MTD finding Stage	STARTED	ARM 1 Dose Level 1 (MTD Level in ARM1)	0
Phase 1 MTD finding Stage	STARTED	ARM 2 Dose Level 1 (MTD Level in ARM2)	0
Phase 1 MTD finding Stage	COMPLETED	ARM 1 Dose Level 0 - (Starting Dose)	6

1 to 10 of 54Source ClinicalTrials.gov

See all 54 participant flow

Adverse events1,179

Each adverse event the trial posted, group by group: the participants affected out of those at risk.

Type	Event	Organ system	Group	Affected	At risk	Events
other	Abdominal pain	Gastrointestinal disorders	ARM 1 Dose Level 0 (Starting Dose)	0	6	0
other	Abdominal pain	Gastrointestinal disorders	ARM 1 Dose Level 1 (Dose Escalation)	0	13	0
other	Abdominal pain	Gastrointestinal disorders	ARM 2 Dose Level 0 (Starting Dose)	0	3	0
other	Abdominal pain	Gastrointestinal disorders	ARM 2 Dose 1 (Dose Escalation)	0	6	0
other	Abdominal pain	Gastrointestinal disorders	ARM 2 Dose 0 (Dose De-escalation)	0	3	0
other	Abdominal pain	Gastrointestinal disorders	ARM 2 Dose Level II (Dose Escalation)	0	2	0
other	Abdominal pain	Gastrointestinal disorders	ARM 2 Dose Level I (Dose De-escalation)	0	7	0
other	Abdominal pain	Gastrointestinal disorders	ARM 1 Dose Level 1 (MTD Level in ARM1)	1	6	2
other	Abdominal pain	Gastrointestinal disorders	ARM 2 Dose Level 1 (MTD Level in ARM2)	1	7	1
other	Activated partial thromboplastin time prolonged	Investigations	ARM 1 Dose Level 0 (Starting Dose)	0	6	0

1 to 10 of 1,179Source ClinicalTrials.gov

See all 1,179 adverse events

Adverse event totals27

The totals the trial posted for each group.

Total	Group	Affected	At risk
Total, all-cause mortality	ARM 1 Dose Level 0 (Starting Dose)	0	6
Total, all-cause mortality	ARM 1 Dose Level 1 (Dose Escalation)	0	13
Total, all-cause mortality	ARM 2 Dose Level 0 (Starting Dose)	2	3
Total, all-cause mortality	ARM 2 Dose 1 (Dose Escalation)	0	6
Total, all-cause mortality	ARM 2 Dose 0 (Dose De-escalation)	1	3
Total, all-cause mortality	ARM 2 Dose Level II (Dose Escalation)	0	2
Total, all-cause mortality	ARM 2 Dose Level I (Dose De-escalation)	1	7
Total, all-cause mortality	ARM 1 Dose Level 1 (MTD Level in ARM1)	0	6
Total, all-cause mortality	ARM 2 Dose Level 1 (MTD Level in ARM2)	0	7
Total, other adverse events	ARM 1 Dose Level 0 (Starting Dose)	6	6

1 to 10 of 27Source ClinicalTrials.gov

See all 27 adverse event totals

Papers1

The papers the trial lists on ClinicalTrials.gov.

PMID	Listed as
15758009	BACKGROUND

Source PubMed

Grants0

The grants NIH RePORTER links to the trial, newest funded first: NIH's, and some of AHRQ's, CDC's, FDA's and VA's. Each shows its title, principal investigators, organization and funder in its newest year.

None in this release.

Trial comparisons0

Comparisons of the trial's two groups, calculated by ConductScience from the counts it posted.

None in this release.

Tests0

The ConductCognition tests this trial's registered outcomes name, as ScienceGraph matched them in trial-tests-2026-11-12-0.2.1.

None in this release.

Data dates

The day each source was copied for this release.

ClinicalTrials.gov: 2026-11-12; ClinicalTrials.gov
Results, from AACT: 2026-03-23; AACT
NIH grant links: 2026-11-13; NIH RePORTER

Sources 3

ClinicalTrials.gov's posted results, through CTTI's AACTFreely available. Acknowledgement requested
ClinicalTrials.govNo license stated
NIH RePORTER's clinical studies and project filesPublic domain

Each source's terms

ClinicalTrials.gov's posted results, through CTTI's AACTClinicalTrials.gov data via Aggregate Analysis of ClinicalTrials.gov (AACT), CTTI. CTTI makes its materials freely available and requests acknowledgement. https://aact.ctti-clinicaltrials.org/documentation/299
ClinicalTrials.govnone stated
NIH RePORTER's clinical studies and project filesPublic domain (NIH RePORTER)

ClinicalTrials.gov's data carry an international copyright outside the United States: https://clinicaltrials.gov/about-site/terms-conditions.

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