Trial Outcomes & Findings for Phase I/II Evaluation of Temozolomide and ZARNESTRA (R115777) for Recurrent and Progressive Glioblastoma Multiforme (NCT NCT00050986)

Last Updated: 2020-09-22

Results Overview

Phase I Dose limiting toxicity evaluation at end of first cycle based on blood tests every two weeks and participants' subjective and objective symptoms. Start Dose Level 100 mg/m² Temozolomide once daily + 400 mg ZARNESTRA twice daily; Dose Level 1 100 mg/m² Temozolomide once daily + 500 mg ZARNESTRA twice daily; Dose Level 2 150 mg/m² Temozolomide once daily + 500 mg ZARNESTRA twice daily; Dose Level 3 150 mg/m² Temozolomide once daily + 600 mg ZARNESTRA twice daily; Dose Level 4 150 mg/m² Temozolomide once daily + 800 mg ZARNESTRA twice daily

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

55 participants

Primary outcome timeframe

End of first cycle (4 weeks) evaluation

Results posted on

2020-09-22

Participant Flow

Total of 55 participants recruited in between 12/30/2002 and 11/30/2005, all at M. D. Anderson Cancer Center.

5 patients were not evaluated for response because of the following: 1 early, non-treatment related death; 3 withdrew consent; 1 discontinued for intercurrent illness (pneumonia).

Participant milestones

Participant milestones
Measure	Temozolomide and R115777
Overall Study STARTED	55
Overall Study COMPLETED	53
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Phase I/II Evaluation of Temozolomide and ZARNESTRA (R115777) for Recurrent and Progressive Glioblastoma Multiforme

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Temozolomide and R115777 n=55 Participants
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	52 Participants n=5 Participants
Age, Categorical >=65 years	3 Participants n=5 Participants
Age, Continuous	52 years n=5 Participants
Sex: Female, Male Female	13 Participants n=5 Participants
Sex: Female, Male Male	42 Participants n=5 Participants
Region of Enrollment United States	55 participants n=5 Participants

PRIMARY outcome

Timeframe: End of first cycle (4 weeks) evaluation

Population: As treated.

Outcome measures

Outcome measures
Measure	Temozolomide and R115777 n=15 Participants
Maximal Tolerating Dose (MTD for Phase I) Dose Level 1	3 participants
Maximal Tolerating Dose (MTD for Phase I) Dose Level 2	3 participants
Maximal Tolerating Dose (MTD for Phase I) Dose Level 3	6 participants
Maximal Tolerating Dose (MTD for Phase I) Dose Level 4	3 participants

SECONDARY outcome

Timeframe: 6 months

Efficacy measured by 6 month progression-free survival assessment.

Outcome measures

Outcome data not reported

Adverse Events

Temozolomide and R115777

Serious events: 24 serious events

Other events: 47 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Temozolomide and R115777 n=53 participants at risk
Vascular disorders Thrombosis/embolism	7.5% 4/53 • Number of events 4 • 2 years, 11 months Including all serious adverse events regardless of attribution. Including all grade 3 or higher adverse events regardless of attribution.
Nervous system disorders Seizure	5.7% 3/53 • Number of events 3 • 2 years, 11 months Including all serious adverse events regardless of attribution. Including all grade 3 or higher adverse events regardless of attribution.
Nervous system disorders Death	3.8% 2/53 • Number of events 2 • 2 years, 11 months Including all serious adverse events regardless of attribution. Including all grade 3 or higher adverse events regardless of attribution.
Blood and lymphatic system disorders Neutrophils	5.7% 3/53 • Number of events 3 • 2 years, 11 months Including all serious adverse events regardless of attribution. Including all grade 3 or higher adverse events regardless of attribution.
Nervous system disorders confusion	1.9% 1/53 • Number of events 1 • 2 years, 11 months Including all serious adverse events regardless of attribution. Including all grade 3 or higher adverse events regardless of attribution.
Blood and lymphatic system disorders Hemoglobin	1.9% 1/53 • Number of events 1 • 2 years, 11 months Including all serious adverse events regardless of attribution. Including all grade 3 or higher adverse events regardless of attribution.
Infections and infestations Herpes Zoster	3.8% 2/53 • Number of events 2 • 2 years, 11 months Including all serious adverse events regardless of attribution. Including all grade 3 or higher adverse events regardless of attribution.
Nervous system disorders Depressed level of consiousness	1.9% 1/53 • Number of events 1 • 2 years, 11 months Including all serious adverse events regardless of attribution. Including all grade 3 or higher adverse events regardless of attribution.
Metabolism and nutrition disorders hypokalemia	3.8% 2/53 • Number of events 2 • 2 years, 11 months Including all serious adverse events regardless of attribution. Including all grade 3 or higher adverse events regardless of attribution.
Metabolism and nutrition disorders hypophasphatemia	1.9% 1/53 • Number of events 1 • 2 years, 11 months Including all serious adverse events regardless of attribution. Including all grade 3 or higher adverse events regardless of attribution.
Nervous system disorders Pyramidal Tract Dysfunction	1.9% 1/53 • Number of events 1 • 2 years, 11 months Including all serious adverse events regardless of attribution. Including all grade 3 or higher adverse events regardless of attribution.
Respiratory, thoracic and mediastinal disorders Pneumonitis	3.8% 2/53 • Number of events 2 • 2 years, 11 months Including all serious adverse events regardless of attribution. Including all grade 3 or higher adverse events regardless of attribution.
Infections and infestations Infection	9.4% 5/53 • Number of events 5 • 2 years, 11 months Including all serious adverse events regardless of attribution. Including all grade 3 or higher adverse events regardless of attribution.
Blood and lymphatic system disorders thrombocytopenia	3.8% 2/53 • Number of events 2 • 2 years, 11 months Including all serious adverse events regardless of attribution. Including all grade 3 or higher adverse events regardless of attribution.
Blood and lymphatic system disorders CNS Hemorrhage	1.9% 1/53 • Number of events 1 • 2 years, 11 months Including all serious adverse events regardless of attribution. Including all grade 3 or higher adverse events regardless of attribution.
Metabolism and nutrition disorders Amyliase, Lipase, Pancreatitis	1.9% 1/53 • Number of events 1 • 2 years, 11 months Including all serious adverse events regardless of attribution. Including all grade 3 or higher adverse events regardless of attribution.

Other adverse events

Other adverse events
Measure	Temozolomide and R115777 n=53 participants at risk
Gastrointestinal disorders Abdominal pain	1.9% 1/53 • Number of events 1 • 2 years, 11 months Including all serious adverse events regardless of attribution. Including all grade 3 or higher adverse events regardless of attribution.
Metabolism and nutrition disorders ALT	3.8% 2/53 • Number of events 2 • 2 years, 11 months Including all serious adverse events regardless of attribution. Including all grade 3 or higher adverse events regardless of attribution.
Blood and lymphatic system disorders Hemoglobin	9.4% 5/53 • Number of events 6 • 2 years, 11 months Including all serious adverse events regardless of attribution. Including all grade 3 or higher adverse events regardless of attribution.
Gastrointestinal disorders Anorexia	1.9% 1/53 • Number of events 1 • 2 years, 11 months Including all serious adverse events regardless of attribution. Including all grade 3 or higher adverse events regardless of attribution.
Nervous system disorders Ataxia	1.9% 1/53 • Number of events 1 • 2 years, 11 months Including all serious adverse events regardless of attribution. Including all grade 3 or higher adverse events regardless of attribution.
Gastrointestinal disorders Constipation	3.8% 2/53 • Number of events 4 • 2 years, 11 months Including all serious adverse events regardless of attribution. Including all grade 3 or higher adverse events regardless of attribution.
Skin and subcutaneous tissue disorders decubitus Ulcer	3.8% 2/53 • Number of events 2 • 2 years, 11 months Including all serious adverse events regardless of attribution. Including all grade 3 or higher adverse events regardless of attribution.
Gastrointestinal disorders Dehydration	3.8% 2/53 • Number of events 2 • 2 years, 11 months Including all serious adverse events regardless of attribution. Including all grade 3 or higher adverse events regardless of attribution.
Gastrointestinal disorders Dry mouth	1.9% 1/53 • Number of events 1 • 2 years, 11 months Including all serious adverse events regardless of attribution. Including all grade 3 or higher adverse events regardless of attribution.
Respiratory, thoracic and mediastinal disorders Dyspnea	1.9% 1/53 • Number of events 1 • 2 years, 11 months Including all serious adverse events regardless of attribution. Including all grade 3 or higher adverse events regardless of attribution.
General disorders Fatigue	13.2% 7/53 • Number of events 12 • 2 years, 11 months Including all serious adverse events regardless of attribution. Including all grade 3 or higher adverse events regardless of attribution.
Metabolism and nutrition disorders Hyperglycemia	11.3% 6/53 • Number of events 11 • 2 years, 11 months Including all serious adverse events regardless of attribution. Including all grade 3 or higher adverse events regardless of attribution.
Blood and lymphatic system disorders Neutrophils	39.6% 21/53 • Number of events 76 • 2 years, 11 months Including all serious adverse events regardless of attribution. Including all grade 3 or higher adverse events regardless of attribution.
Ear and labyrinth disorders Hearing	1.9% 1/53 • Number of events 1 • 2 years, 11 months Including all serious adverse events regardless of attribution. Including all grade 3 or higher adverse events regardless of attribution.
Metabolism and nutrition disorders Hyperuricemia	1.9% 1/53 • Number of events 1 • 2 years, 11 months Including all serious adverse events regardless of attribution. Including all grade 3 or higher adverse events regardless of attribution.
Metabolism and nutrition disorders Hypoalbuminemia	1.9% 1/53 • Number of events 1 • 2 years, 11 months Including all serious adverse events regardless of attribution. Including all grade 3 or higher adverse events regardless of attribution.
Metabolism and nutrition disorders Hypocalcemia	1.9% 1/53 • Number of events 1 • 2 years, 11 months Including all serious adverse events regardless of attribution. Including all grade 3 or higher adverse events regardless of attribution.
Metabolism and nutrition disorders Hypokalemia	3.8% 2/53 • Number of events 4 • 2 years, 11 months Including all serious adverse events regardless of attribution. Including all grade 3 or higher adverse events regardless of attribution.
Metabolism and nutrition disorders Hyponatremia	3.8% 2/53 • Number of events 2 • 2 years, 11 months Including all serious adverse events regardless of attribution. Including all grade 3 or higher adverse events regardless of attribution.
Metabolism and nutrition disorders Hypophosphatemia	7.5% 4/53 • Number of events 5 • 2 years, 11 months Including all serious adverse events regardless of attribution. Including all grade 3 or higher adverse events regardless of attribution.
Cardiac disorders Hypotension	1.9% 1/53 • Number of events 1 • 2 years, 11 months Including all serious adverse events regardless of attribution. Including all grade 3 or higher adverse events regardless of attribution.
Respiratory, thoracic and mediastinal disorders Hypoxia	1.9% 1/53 • Number of events 1 • 2 years, 11 months Including all serious adverse events regardless of attribution. Including all grade 3 or higher adverse events regardless of attribution.
Blood and lymphatic system disorders Lymphocytopenia	75.5% 40/53 • Number of events 210 • 2 years, 11 months Including all serious adverse events regardless of attribution. Including all grade 3 or higher adverse events regardless of attribution.
Nervous system disorders Mental Status	5.7% 3/53 • Number of events 3 • 2 years, 11 months Including all serious adverse events regardless of attribution. Including all grade 3 or higher adverse events regardless of attribution.
Nervous system disorders Motor	11.3% 6/53 • Number of events 6 • 2 years, 11 months Including all serious adverse events regardless of attribution. Including all grade 3 or higher adverse events regardless of attribution.
Musculoskeletal and connective tissue disorders Muscle weakness	7.5% 4/53 • Number of events 4 • 2 years, 11 months Including all serious adverse events regardless of attribution. Including all grade 3 or higher adverse events regardless of attribution.
General disorders Pain	11.3% 6/53 • Number of events 8 • 2 years, 11 months Including all serious adverse events regardless of attribution. Including all grade 3 or higher adverse events regardless of attribution.
Gastrointestinal disorders Nausea	1.9% 1/53 • Number of events 1 • 2 years, 11 months Including all serious adverse events regardless of attribution. Including all grade 3 or higher adverse events regardless of attribution.
Nervous system disorders Personality/behavioral	3.8% 2/53 • Number of events 2 • 2 years, 11 months Including all serious adverse events regardless of attribution. Including all grade 3 or higher adverse events regardless of attribution.
Blood and lymphatic system disorders Thrombocytopenia	30.2% 16/53 • Number of events 30 • 2 years, 11 months Including all serious adverse events regardless of attribution. Including all grade 3 or higher adverse events regardless of attribution.
Respiratory, thoracic and mediastinal disorders Pneumonits	7.5% 4/53 • Number of events 4 • 2 years, 11 months Including all serious adverse events regardless of attribution. Including all grade 3 or higher adverse events regardless of attribution.
Skin and subcutaneous tissue disorders Pruritus	1.9% 1/53 • Number of events 2 • 2 years, 11 months Including all serious adverse events regardless of attribution. Including all grade 3 or higher adverse events regardless of attribution.
Nervous system disorders Seizures	7.5% 4/53 • Number of events 4 • 2 years, 11 months Including all serious adverse events regardless of attribution. Including all grade 3 or higher adverse events regardless of attribution.
Nervous system disorders Speech impairment	1.9% 1/53 • Number of events 1 • 2 years, 11 months Including all serious adverse events regardless of attribution. Including all grade 3 or higher adverse events regardless of attribution.
Nervous system disorders Syncope	1.9% 1/53 • Number of events 1 • 2 years, 11 months Including all serious adverse events regardless of attribution. Including all grade 3 or higher adverse events regardless of attribution.
Blood and lymphatic system disorders Thrombosis	5.7% 3/53 • Number of events 3 • 2 years, 11 months Including all serious adverse events regardless of attribution. Including all grade 3 or higher adverse events regardless of attribution.
General disorders Weight gain	1.9% 1/53 • Number of events 1 • 2 years, 11 months Including all serious adverse events regardless of attribution. Including all grade 3 or higher adverse events regardless of attribution.
General disorders Weight loss	1.9% 1/53 • Number of events 1 • 2 years, 11 months Including all serious adverse events regardless of attribution. Including all grade 3 or higher adverse events regardless of attribution.

Additional Information

W.K. Yung,MD/Clinical Professor, Neuro-Oncology

University of Texas, M. D. Anderson Cancer Center

Phone: (713) 794-1285

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place