Trial Outcomes & Findings for A Study of Gliadel Followed by Avastin + Irinotecan for Glioblastoma Multiforme (GBM) (NCT NCT00735436)

NCT ID: NCT00735436

Last Updated: 2013-02-11

Results Overview

The percentage of participants surviving 24 weeks from the start of study treatment

• Recruitment status: TERMINATED
• Study phase: PHASE2
• Target enrollment: 18 participants
• Primary outcome timeframe: 24 weeks
• Results posted on: 2013-02-11

Participant Flow

Participant milestones

Measure	Gliadel/Avastin/CPT-11 Gliadel wafers (1-8) inserted at time of gross total resection. CPT-11 (Irinotecan): 125 mg/m2 (no enzyme-inducing anticonvulsant drugs) or 340 mg/m2 (enzyme-inducing anticonvulsant drugs) given every two weeks on days 1, 15, 29 of each 42 day cycle, up to 12 cycles. If the patient has the uridine diphosphate (UDP) glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1) polymorphism (7/7), they do not metabolize the irinotecan normally, so these patients will start out at a two dose level reduction. For patients on an enzyme-inducing anti-epileptic drugs (EIAED), the starting dose will be 275 mg/M2, and for patients not on an EIAED, the starting dose will be 75 mg/M2. Avastin: 10 mg/kg immediately after the irinotecan given every 2 weeks on days 1, 15, 29 of each 42 day cycle.
Overall Study STARTED	18
Overall Study COMPLETED	18
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Study of Gliadel Followed by Avastin + Irinotecan for Glioblastoma Multiforme (GBM)

Baseline characteristics by cohort

Measure	Gliadel/Avastin/CPT-11 n=18 Participants Gliadel/Avastin/CPT-11
Age Continuous	55.3 years STANDARD_DEVIATION 11.5 • n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants
Sex: Female, Male Male	13 Participants n=5 Participants

PRIMARY outcome

Timeframe: 24 weeks

Population: intent-to-treat

The percentage of participants surviving 24 weeks from the start of study treatment

Outcome measures

Measure	Gliadel/Avastin/CPT-11 n=18 Participants Gliadel/Avastin/CPT-11
24-week Overall Survival	77.8 percentage of participants Interval 51.1 to 91.0

SECONDARY outcome

Timeframe: 24 weeks

Population: intent-to-treat

The percentage of participants surviving 24 weeks from the start of study treatment without progression of disease. PFS was defined as the time from the date of study treatment initiation to the date of the first documented progression according to modified Macdonald criteria, or to death due to any cause.

Outcome measures

Measure	Gliadel/Avastin/CPT-11 n=18 Participants Gliadel/Avastin/CPT-11
24-week Progression-free Survival (PFS)	61.1 percentage of participants Interval 35.3 to 79.2

SECONDARY outcome

Timeframe: Time in months from the start of study treatment to the date of first progression according to modified Macdonald criteria or to death due to any cause, assessed up to 47 months

Population: intent-to-treat

Time in months from the start of study treatment to the date of first progression according to modified Macdonald criteria, or to death due to any cause. Patients alive who had not progressed as of the last follow-up had PFS censored at the last follow-up date. Median PFS was estimated using a Kaplan-Meier curve.

Outcome measures

Measure	Gliadel/Avastin/CPT-11 n=18 Participants Gliadel/Avastin/CPT-11
Median Progression-free Survival (PFS)	8 months Interval 3.2 to 15.8

SECONDARY outcome

Timeframe: Time in months from the start of study treatment to date of death due to any cause, assessed up to 47 months

Population: intent-to-treat

Time in months from the start of study treatment to date of death due to any cause. Patients alive at last follow-up are censored as of that follow-up date. Median OS was estimated using a Kaplan-Meier curve.

Outcome measures

Measure	Gliadel/Avastin/CPT-11 n=18 Participants Gliadel/Avastin/CPT-11
Median Overall Survival (OS)	13.5 months Interval 6.0 to 19.5

SECONDARY outcome

Timeframe: 47 months

Population: intent-to-treat

Incidence and severity of CNS hemorrhage

Outcome measures

Measure	Gliadel/Avastin/CPT-11 n=18 Participants Gliadel/Avastin/CPT-11
Incidence and Severity of Central Nervous System (CNS) Hemorrhage Grade 5 CNS Hemorrhage	1 participants
Incidence and Severity of Central Nervous System (CNS) Hemorrhage Grade 4 CNS Hemorrhage	0 participants

SECONDARY outcome

Timeframe: 47 months

Population: intent-to-treat

Incidence of grade ≥ 4 hematologic and ≥ grade 3 non-hematologic toxicities

Outcome measures

Measure	Gliadel/Avastin/CPT-11 n=18 Participants Gliadel/Avastin/CPT-11
Incidence of Grade ≥ 4 Hematologic and ≥ Grade 3 Non-hematologic Toxicities Grade >= 4 Hematologic Toxicity	0 participants
Incidence of Grade ≥ 4 Hematologic and ≥ Grade 3 Non-hematologic Toxicities Grade >= 3 Non-hematologic Toxicity	2 participants

Adverse Events

Gliadel/Avastin/CPT-11

Serious events: 8 serious events

Other events: 14 other events

Deaths: 0 deaths

Serious adverse events

Measure	Gliadel/Avastin/CPT-11 n=18 participants at risk Gliadel/Avastin/CPT-11
Infections and infestations Lung infection	5.6% 1/18 • 47 months Adverse Events were collected for the study using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, but were converted to CTCAE version 4.0 for entry in ClinicalTrials.gov.
Infections and infestations Wound infection	16.7% 3/18 • 47 months Adverse Events were collected for the study using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, but were converted to CTCAE version 4.0 for entry in ClinicalTrials.gov.
Injury, poisoning and procedural complications Wound dihiscence	5.6% 1/18 • 47 months Adverse Events were collected for the study using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, but were converted to CTCAE version 4.0 for entry in ClinicalTrials.gov.
Musculoskeletal and connective tissue disorders Back pain	5.6% 1/18 • 47 months Adverse Events were collected for the study using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, but were converted to CTCAE version 4.0 for entry in ClinicalTrials.gov.
Nervous system disorders Cognitive disturbance	11.1% 2/18 • 47 months Adverse Events were collected for the study using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, but were converted to CTCAE version 4.0 for entry in ClinicalTrials.gov.
Nervous system disorders Encephalopathy	5.6% 1/18 • 47 months Adverse Events were collected for the study using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, but were converted to CTCAE version 4.0 for entry in ClinicalTrials.gov.
Nervous system disorders Intracranial hemorrhage	5.6% 1/18 • 47 months Adverse Events were collected for the study using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, but were converted to CTCAE version 4.0 for entry in ClinicalTrials.gov.
Nervous system disorders Ischemia cerebrovascular	5.6% 1/18 • 47 months Adverse Events were collected for the study using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, but were converted to CTCAE version 4.0 for entry in ClinicalTrials.gov.
Nervous system disorders Peripheral motor neuropathy	16.7% 3/18 • 47 months Adverse Events were collected for the study using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, but were converted to CTCAE version 4.0 for entry in ClinicalTrials.gov.
Nervous system disorders Peripheral sensory neuropathy	5.6% 1/18 • 47 months Adverse Events were collected for the study using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, but were converted to CTCAE version 4.0 for entry in ClinicalTrials.gov.
Nervous system disorders Seizure	16.7% 3/18 • 47 months Adverse Events were collected for the study using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, but were converted to CTCAE version 4.0 for entry in ClinicalTrials.gov.

Other adverse events

Measure	Gliadel/Avastin/CPT-11 n=18 participants at risk Gliadel/Avastin/CPT-11
Blood and lymphatic system disorders Anemia	44.4% 8/18 • 47 months Adverse Events were collected for the study using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, but were converted to CTCAE version 4.0 for entry in ClinicalTrials.gov.
Eye disorders Eye disorders-Other, specify: decreased vision	5.6% 1/18 • 47 months Adverse Events were collected for the study using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, but were converted to CTCAE version 4.0 for entry in ClinicalTrials.gov.
Gastrointestinal disorders Constipation	5.6% 1/18 • 47 months Adverse Events were collected for the study using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, but were converted to CTCAE version 4.0 for entry in ClinicalTrials.gov.
Gastrointestinal disorders Diarrhea	22.2% 4/18 • 47 months Adverse Events were collected for the study using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, but were converted to CTCAE version 4.0 for entry in ClinicalTrials.gov.
Gastrointestinal disorders Nausea	16.7% 3/18 • 47 months Adverse Events were collected for the study using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, but were converted to CTCAE version 4.0 for entry in ClinicalTrials.gov.
Gastrointestinal disorders Vomiting	11.1% 2/18 • 47 months Adverse Events were collected for the study using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, but were converted to CTCAE version 4.0 for entry in ClinicalTrials.gov.
General disorders Edema limbs	5.6% 1/18 • 47 months Adverse Events were collected for the study using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, but were converted to CTCAE version 4.0 for entry in ClinicalTrials.gov.
General disorders Fatigue	5.6% 1/18 • 47 months Adverse Events were collected for the study using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, but were converted to CTCAE version 4.0 for entry in ClinicalTrials.gov.
Infections and infestations Bronchial infection	5.6% 1/18 • 47 months Adverse Events were collected for the study using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, but were converted to CTCAE version 4.0 for entry in ClinicalTrials.gov.
Infections and infestations Sepsis	5.6% 1/18 • 47 months Adverse Events were collected for the study using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, but were converted to CTCAE version 4.0 for entry in ClinicalTrials.gov.
Infections and infestations Tooth infection	5.6% 1/18 • 47 months Adverse Events were collected for the study using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, but were converted to CTCAE version 4.0 for entry in ClinicalTrials.gov.
Infections and infestations Urinary tract infection	11.1% 2/18 • 47 months Adverse Events were collected for the study using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, but were converted to CTCAE version 4.0 for entry in ClinicalTrials.gov.
Infections and infestations Wound infection	5.6% 1/18 • 47 months Adverse Events were collected for the study using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, but were converted to CTCAE version 4.0 for entry in ClinicalTrials.gov.
Investigations Alanine aminotransferase increased	11.1% 2/18 • 47 months Adverse Events were collected for the study using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, but were converted to CTCAE version 4.0 for entry in ClinicalTrials.gov.
Investigations Alkaline phosphatase increased	5.6% 1/18 • 47 months Adverse Events were collected for the study using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, but were converted to CTCAE version 4.0 for entry in ClinicalTrials.gov.
Investigations Aspartate aminotransferase increased	5.6% 1/18 • 47 months Adverse Events were collected for the study using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, but were converted to CTCAE version 4.0 for entry in ClinicalTrials.gov.
Investigations Investigations-Other, specify: Ammonia elevated	5.6% 1/18 • 47 months Adverse Events were collected for the study using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, but were converted to CTCAE version 4.0 for entry in ClinicalTrials.gov.
Investigations Investigations-Other, specify: Total Protein Elevated Intermittently	5.6% 1/18 • 47 months Adverse Events were collected for the study using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, but were converted to CTCAE version 4.0 for entry in ClinicalTrials.gov.
Investigations Neutrophil count decreased	11.1% 2/18 • 47 months Adverse Events were collected for the study using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, but were converted to CTCAE version 4.0 for entry in ClinicalTrials.gov.
Investigations Platelet count decreased	27.8% 5/18 • 47 months Adverse Events were collected for the study using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, but were converted to CTCAE version 4.0 for entry in ClinicalTrials.gov.
Investigations White blood cell decreased	22.2% 4/18 • 47 months Adverse Events were collected for the study using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, but were converted to CTCAE version 4.0 for entry in ClinicalTrials.gov.
Metabolism and nutrition disorders Hyperglycemia	33.3% 6/18 • 47 months Adverse Events were collected for the study using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, but were converted to CTCAE version 4.0 for entry in ClinicalTrials.gov.
Metabolism and nutrition disorders Hypokalemia	16.7% 3/18 • 47 months Adverse Events were collected for the study using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, but were converted to CTCAE version 4.0 for entry in ClinicalTrials.gov.
Metabolism and nutrition disorders Hyponatremia	11.1% 2/18 • 47 months Adverse Events were collected for the study using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, but were converted to CTCAE version 4.0 for entry in ClinicalTrials.gov.
Nervous system disorders Ataxia	16.7% 3/18 • 47 months Adverse Events were collected for the study using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, but were converted to CTCAE version 4.0 for entry in ClinicalTrials.gov.
Nervous system disorders Cerebrospinal fluid leakage	5.6% 1/18 • 47 months Adverse Events were collected for the study using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, but were converted to CTCAE version 4.0 for entry in ClinicalTrials.gov.
Nervous system disorders Dizziness	11.1% 2/18 • 47 months Adverse Events were collected for the study using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, but were converted to CTCAE version 4.0 for entry in ClinicalTrials.gov.
Nervous system disorders Dysphasia	5.6% 1/18 • 47 months Adverse Events were collected for the study using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, but were converted to CTCAE version 4.0 for entry in ClinicalTrials.gov.
Nervous system disorders Headache	22.2% 4/18 • 47 months Adverse Events were collected for the study using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, but were converted to CTCAE version 4.0 for entry in ClinicalTrials.gov.
Nervous system disorders Seizure	5.6% 1/18 • 47 months Adverse Events were collected for the study using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, but were converted to CTCAE version 4.0 for entry in ClinicalTrials.gov.
Nervous system disorders Tremor	5.6% 1/18 • 47 months Adverse Events were collected for the study using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, but were converted to CTCAE version 4.0 for entry in ClinicalTrials.gov.
Psychiatric disorders Depression	5.6% 1/18 • 47 months Adverse Events were collected for the study using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, but were converted to CTCAE version 4.0 for entry in ClinicalTrials.gov.
Vascular disorders Thromboembolic event	11.1% 2/18 • 47 months Adverse Events were collected for the study using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, but were converted to CTCAE version 4.0 for entry in ClinicalTrials.gov.
Metabolism and nutrition disorders Hypoalbuminemia	5.6% 1/18 • 47 months Adverse Events were collected for the study using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, but were converted to CTCAE version 4.0 for entry in ClinicalTrials.gov.
Metabolism and nutrition disorders Hypocalcemia	22.2% 4/18 • 47 months Adverse Events were collected for the study using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, but were converted to CTCAE version 4.0 for entry in ClinicalTrials.gov.

Additional Information

Annick Desjardins, MD, FRCPC

Duke University Medical Center

Email: annick.desjardins@dm.duke.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place