Trial Outcomes & Findings for A Study of Intraventricular Liposomal Encapsulated Ara-C (DepoCyt) in Patients With Recurrent Glioblastoma (NCT NCT01044966)

Results Overview

The type and number of adverse events will be recorded and reported by the number of participants with treatment-related adverse events as assessed by CTCAE v4.0

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

12 participants

Primary outcome timeframe

52 weeks

Results posted on

2019-02-12

Participant Flow

Participant milestones

Participant milestones
Measure	ITV DepoCyt + Temozolomide Patients will undergo an induction phase of intraventricular (ITV) DepoCyt, using the dosage determined from the Phase I portionPatients with stable disease (clinically and radiographically), not exhibiting systemic toxicity, will undergo a three month consolidation phase of ITV DepoCyt, for one month (Cycles 3-6). Patients without progression or toxicity will undergo maintenance therapy using ITV DepoCyt every four weeks (+/- 3 days) for a maximum of 8 months (cycles 7-14) or until recurrence or toxicity ensues. ITV DepoCyt + Temozolomide: Intrathecal liposomal Ara-C dosing will begin at 50 mg ITV every 2-4 weeks, and de-escalated based on toxicity obtained from the Phase I portion of the trial. Metronomic dosing of temozolomide will be given at 75 mg/m2 for 21 days (continuous ora
Induction Phase STARTED	12
Induction Phase COMPLETED	12
Induction Phase NOT COMPLETED	0
Consolidation Phase STARTED	12
Consolidation Phase COMPLETED	2
Consolidation Phase NOT COMPLETED	10

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Study of Intraventricular Liposomal Encapsulated Ara-C (DepoCyt) in Patients With Recurrent Glioblastoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	ITV DepoCyt + Temozolomide n=12 Participants Patients will undergo an induction phase of intraventricular (ITV) DepoCyt, using the dosage determined from the Phase I portionPatients with stable disease (clinically and radiographically), not exhibiting systemic toxicity, will undergo a three month consolidation phase of ITV DepoCyt, for one month (Cycles 3-6). Patients without progression or toxicity will undergo maintenance therapy using ITV DepoCyt every four weeks (+/- 3 days) for a maximum of 8 months (cycles 7-14) or until recurrence or toxicity ensues. ITV DepoCyt + Temozolomide: Intrathecal liposomal Ara-C dosing will begin at 50 mg ITV every 2-4 weeks, and de-escalated based on toxicity obtained from the Phase I portion of the trial. Metronomic dosing of temozolomide will be given at 75 mg/m2 for 21 days (continuous ora
Age, Categorical <=18 years	0 Participants n=93 Participants
Age, Categorical Between 18 and 65 years	9 Participants n=93 Participants
Age, Categorical >=65 years	3 Participants n=93 Participants
Age, Continuous	52.9 years n=93 Participants
Sex: Female, Male Female	3 Participants n=93 Participants
Sex: Female, Male Male	9 Participants n=93 Participants
Region of Enrollment United States	12 participants n=93 Participants

PRIMARY outcome

Timeframe: 52 weeks

The type and number of adverse events will be recorded and reported by the number of participants with treatment-related adverse events as assessed by CTCAE v4.0

Outcome measures

Outcome measures
Measure	ITV DepoCyt + Temozolomide n=12 Participants Patients will undergo an induction phase of intraventricular (ITV) DepoCyt, using the dosage determined from the Phase I portionPatients with stable disease (clinically and radiographically), not exhibiting systemic toxicity, will undergo a three month consolidation phase of ITV DepoCyt, for one month (Cycles 3-6). Patients without progression or toxicity will undergo maintenance therapy using ITV DepoCyt every four weeks (+/- 3 days) for a maximum of 8 months (cycles 7-14) or until recurrence or toxicity ensues. ITV DepoCyt + Temozolomide: Intrathecal liposomal Ara-C dosing will begin at 50 mg ITV every 2-4 weeks, and de-escalated based on toxicity obtained from the Phase I portion of the trial. Metronomic dosing of temozolomide will be given at 75 mg/m2 for 21 days (continuous oral dosing), followed by 7 days off in a 28 day cycle as a once daily dosing regimen.
Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0	12 Participants

SECONDARY outcome

Timeframe: 16 weeks

Eligibility of patients with GBM that are able to receive study drug to estimate the proportion of patients with recurrent GBM treated with ITV DepoCyt in combination with oral temozolomide who are progression-free at 16 weeks. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Outcome measures

Outcome measures
Measure	ITV DepoCyt + Temozolomide n=12 Participants Patients will undergo an induction phase of intraventricular (ITV) DepoCyt, using the dosage determined from the Phase I portionPatients with stable disease (clinically and radiographically), not exhibiting systemic toxicity, will undergo a three month consolidation phase of ITV DepoCyt, for one month (Cycles 3-6). Patients without progression or toxicity will undergo maintenance therapy using ITV DepoCyt every four weeks (+/- 3 days) for a maximum of 8 months (cycles 7-14) or until recurrence or toxicity ensues. ITV DepoCyt + Temozolomide: Intrathecal liposomal Ara-C dosing will begin at 50 mg ITV every 2-4 weeks, and de-escalated based on toxicity obtained from the Phase I portion of the trial. Metronomic dosing of temozolomide will be given at 75 mg/m2 for 21 days (continuous oral dosing), followed by 7 days off in a 28 day cycle as a once daily dosing regimen.
Proportion of Patients With Recurrent GBM Treated With ITV DepoCyt in Combination With Oral Temozolomide Who Are Progression-free at 16 Weeks.	12 Participants

SECONDARY outcome

Timeframe: At 6 months

The progression free survival of patients receiving study drug will be recorded. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Outcome measures

Outcome measures
Measure	ITV DepoCyt + Temozolomide n=12 Participants Patients will undergo an induction phase of intraventricular (ITV) DepoCyt, using the dosage determined from the Phase I portionPatients with stable disease (clinically and radiographically), not exhibiting systemic toxicity, will undergo a three month consolidation phase of ITV DepoCyt, for one month (Cycles 3-6). Patients without progression or toxicity will undergo maintenance therapy using ITV DepoCyt every four weeks (+/- 3 days) for a maximum of 8 months (cycles 7-14) or until recurrence or toxicity ensues. ITV DepoCyt + Temozolomide: Intrathecal liposomal Ara-C dosing will begin at 50 mg ITV every 2-4 weeks, and de-escalated based on toxicity obtained from the Phase I portion of the trial. Metronomic dosing of temozolomide will be given at 75 mg/m2 for 21 days (continuous oral dosing), followed by 7 days off in a 28 day cycle as a once daily dosing regimen.
Progression Free Survival	2 Participants

SECONDARY outcome

Timeframe: 52 weeks

Those responding to study drug will be recorded. Response will be defined as stable neurological examination in conjunction with the absence of progression as defined above.

Outcome measures

Outcome measures
Measure	ITV DepoCyt + Temozolomide n=12 Participants Patients will undergo an induction phase of intraventricular (ITV) DepoCyt, using the dosage determined from the Phase I portionPatients with stable disease (clinically and radiographically), not exhibiting systemic toxicity, will undergo a three month consolidation phase of ITV DepoCyt, for one month (Cycles 3-6). Patients without progression or toxicity will undergo maintenance therapy using ITV DepoCyt every four weeks (+/- 3 days) for a maximum of 8 months (cycles 7-14) or until recurrence or toxicity ensues. ITV DepoCyt + Temozolomide: Intrathecal liposomal Ara-C dosing will begin at 50 mg ITV every 2-4 weeks, and de-escalated based on toxicity obtained from the Phase I portion of the trial. Metronomic dosing of temozolomide will be given at 75 mg/m2 for 21 days (continuous oral dosing), followed by 7 days off in a 28 day cycle as a once daily dosing regimen.
Response Rate of Drug Treatment	2 Participants

SECONDARY outcome

Timeframe: 52 weeks

Participants recorded are those who had an improvement in QOL score, QOL outcomes will be assessed and recorded using the EORTC QLQ C30 version 3. This 30 question questionnaire will be used to asses our patient overall feeling of well-being during the trial. Questions to assess quality of life are measured from 1-4 with the following graded values: 1. Not at all 2. A little 3. Quite a bit 4. Very much Lower total scores are consistent with better quality of life and changes of greater or equal to 10 points are considered a significant change in quality of life.

Outcome measures

Outcome measures
Measure	ITV DepoCyt + Temozolomide n=12 Participants Patients will undergo an induction phase of intraventricular (ITV) DepoCyt, using the dosage determined from the Phase I portionPatients with stable disease (clinically and radiographically), not exhibiting systemic toxicity, will undergo a three month consolidation phase of ITV DepoCyt, for one month (Cycles 3-6). Patients without progression or toxicity will undergo maintenance therapy using ITV DepoCyt every four weeks (+/- 3 days) for a maximum of 8 months (cycles 7-14) or until recurrence or toxicity ensues. ITV DepoCyt + Temozolomide: Intrathecal liposomal Ara-C dosing will begin at 50 mg ITV every 2-4 weeks, and de-escalated based on toxicity obtained from the Phase I portion of the trial. Metronomic dosing of temozolomide will be given at 75 mg/m2 for 21 days (continuous oral dosing), followed by 7 days off in a 28 day cycle as a once daily dosing regimen.
Quality of Life Outcomes Measurement	2 Participants

Adverse Events

ITV DepoCyt + Temozolomide

Serious events: 1 serious events

Other events: 1 other events

Deaths: 12 deaths

Serious adverse events

Serious adverse events
Measure	ITV DepoCyt + Temozolomide n=12 participants at risk Patients will undergo an induction phase of intraventricular (ITV) DepoCyt, using the dosage determined from the Phase I portionPatients with stable disease (clinically and radiographically), not exhibiting systemic toxicity, will undergo a three month consolidation phase of ITV DepoCyt, for one month (Cycles 3-6). Patients without progression or toxicity will undergo maintenance therapy using ITV DepoCyt every four weeks (+/- 3 days) for a maximum of 8 months (cycles 7-14) or until recurrence or toxicity ensues. ITV DepoCyt + Temozolomide: Intrathecal liposomal Ara-C dosing will begin at 50 mg ITV every 2-4 weeks, and de-escalated based on toxicity obtained from the Phase I portion of the trial. Metronomic dosing of temozolomide will be given at 75 mg/m2 for 21 days (continuous ora
Surgical and medical procedures CSF leak	8.3% 1/12 • Number of events 1

Other adverse events

Other adverse events
Measure	ITV DepoCyt + Temozolomide n=12 participants at risk Patients will undergo an induction phase of intraventricular (ITV) DepoCyt, using the dosage determined from the Phase I portionPatients with stable disease (clinically and radiographically), not exhibiting systemic toxicity, will undergo a three month consolidation phase of ITV DepoCyt, for one month (Cycles 3-6). Patients without progression or toxicity will undergo maintenance therapy using ITV DepoCyt every four weeks (+/- 3 days) for a maximum of 8 months (cycles 7-14) or until recurrence or toxicity ensues. ITV DepoCyt + Temozolomide: Intrathecal liposomal Ara-C dosing will begin at 50 mg ITV every 2-4 weeks, and de-escalated based on toxicity obtained from the Phase I portion of the trial. Metronomic dosing of temozolomide will be given at 75 mg/m2 for 21 days (continuous ora
Nervous system disorders seizure	8.3% 1/12 • Number of events 1

Additional Information

Dr. Bruce Frankel

Medical University of South Carolina

Phone: 8437922052

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place