Trial Outcomes & Findings for Cyclophosphamide, Topotecan, and Bevacizumab (CTB) in Patients With Relapsed/Refractory Ewing's Sarcoma and Neuroblastoma (NCT NCT01492673)

Last Updated: 2019-10-29

Results Overview

as measured by objective response rate (CR/PR) after 2 cycles of treatment and duration of response. after 2 cycles of treatment and duration of response according to the Revised RECIST guideline (version 1.1) Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

9 participants

Primary outcome timeframe

2 years

Results posted on

2019-10-29

Participant Flow

Participant milestones

Participant milestones
Measure	Cyclophosphamide, Topotecan, and Bevacizumab (CTB) This is a multi-center, open label phase II study evaluating the safety and efficacy of the novel combination of agents consisting of bevacizumab, cyclophosphamide, and topotecan. Cyclophosphamide, Topotecan, and Bevacizumab: The treatment schedule for this study will consist of a 21-day cycle. Dose modification will only occur with administration of the investigational agent, bevacizumab. The schedule of administration is summarized as follows. Administration of bevacizumab will precede the administration of the cyclophosphamide and topotecan by 3 days (Day - 3) to allow for vascular stabilization prior to initiation of chemotherapy. The chemotherapy backbone will consist of cyclophosphamide and topotecan administered as follows: cyclophosphamide 250 mg/m2/day IV over 30 minutes ± 5 minutes on Days 0-4 followed by topotecan 0.75 mg/m2/day IV over 30 minutes ± 5 minutes on Day 0-4 of every cycle. The dosing of cyclophosphamide and topotecan will be fixed.
Overall Study STARTED	9
Overall Study COMPLETED	9
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Cyclophosphamide, Topotecan, and Bevacizumab (CTB) in Patients With Relapsed/Refractory Ewing's Sarcoma and Neuroblastoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cyclophosphamide, Topotecan, and Bevacizumab (CTB) n=9 Participants This is a multi-center, open label phase II study evaluating the safety and efficacy of the novel combination of agents consisting of bevacizumab, cyclophosphamide, and topotecan. Cyclophosphamide, Topotecan, and Bevacizumab: The treatment schedule for this study will consist of a 21-day cycle. Dose modification will only occur with administration of the investigational agent, bevacizumab. The schedule of administration is summarized as follows. Administration of bevacizumab will precede the administration of the cyclophosphamide and topotecan by 3 days (Day - 3) to allow for vascular stabilization prior to initiation of chemotherapy. The chemotherapy backbone will consist of cyclophosphamide and topotecan administered as follows: cyclophosphamide 250 mg/m2/day IV over 30 minutes ± 5 minutes on Days 0-4 followed by topotecan 0.75 mg/m2/day IV over 30 minutes ± 5 minutes on Day 0-4 of every cycle. The dosing of cyclophosphamide and topotecan will be fixed.
Age, Continuous	12 years n=93 Participants
Sex: Female, Male Female	6 Participants n=93 Participants
Sex: Female, Male Male	3 Participants n=93 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=93 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	9 Participants n=93 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants
Race (NIH/OMB) Black or African American	4 Participants n=93 Participants
Race (NIH/OMB) White	5 Participants n=93 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants
Region of Enrollment Canada	1 participants n=93 Participants
Region of Enrollment United States	8 participants n=93 Participants

PRIMARY outcome

Timeframe: 2 years

Population: Data were not collected. Study terminated due to low accrual.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 2 years

Safety will be assessed by physical examination, interim history, and laboratory assessments. Adverse events will be graded according to the NCI-CTCAE, version 4.0

Outcome measures

Outcome measures
Measure	Cyclophosphamide, Topotecan, and Bevacizumab (CTB) n=9 Participants This is a multi-center, open label phase II study evaluating the safety and efficacy of the novel combination of agents consisting of bevacizumab, cyclophosphamide, and topotecan. Cyclophosphamide, Topotecan, and Bevacizumab: The treatment schedule for this study will consist of a 21-day cycle. Dose modification will only occur with administration of the investigational agent, bevacizumab. The schedule of administration is summarized as follows. Administration of bevacizumab will precede the administration of the cyclophosphamide and topotecan by 3 days (Day - 3) to allow for vascular stabilization prior to initiation of chemotherapy. The chemotherapy backbone will consist of cyclophosphamide and topotecan administered as follows: cyclophosphamide 250 mg/m2/day IV over 30 minutes ± 5 minutes on Days 0-4 followed by topotecan 0.75 mg/m2/day IV over 30 minutes ± 5 minutes on Day 0-4 of every cycle. The dosing of cyclophosphamide and topotecan will be fixed.
Number of Participants With Adverse Events	9 Participants

Adverse Events

Cyclophosphamide, Topotecan, and Bevacizumab (CTB)

Serious events: 7 serious events

Other events: 7 other events

Deaths: 6 deaths

Serious adverse events

Serious adverse events
Measure	Cyclophosphamide, Topotecan, and Bevacizumab (CTB) n=9 participants at risk This is a multi-center, open label phase II study evaluating the safety and efficacy of the novel combination of agents consisting of bevacizumab, cyclophosphamide, and topotecan. Cyclophosphamide, Topotecan, and Bevacizumab: The treatment schedule for this study will consist of a 21-day cycle. Dose modification will only occur with administration of the investigational agent, bevacizumab. The schedule of administration is summarized as follows. Administration of bevacizumab will precede the administration of the cyclophosphamide and topotecan by 3 days (Day - 3) to allow for vascular stabilization prior to initiation of chemotherapy. The chemotherapy backbone will consist of cyclophosphamide and topotecan administered as follows: cyclophosphamide 250 mg/m2/day IV over 30 minutes ± 5 minutes on Days 0-4 followed by topotecan 0.75 mg/m2/day IV over 30 minutes ± 5 minutes on Day 0-4 of every cycle. The dosing of cyclophosphamide and topotecan will be fixed.
Investigations Alanine aminotransferase increased	11.1% 1/9 • 2 years
Blood and lymphatic system disorders Anemia	11.1% 1/9 • 2 years
Investigations Aspartate aminotransferase increased	11.1% 1/9 • 2 years
Musculoskeletal and connective tissue disorders Back pain	11.1% 1/9 • 2 years
Blood and lymphatic system disorders Febrile neutropenia	66.7% 6/9 • 2 years
Investigations Lymphocyte count decreased	44.4% 4/9 • 2 years
Investigations Neutrophil count decreased	11.1% 1/9 • 2 years
Gastrointestinal disorders Oral pain	11.1% 1/9 • 2 years
Investigations Platelet count decreased	77.8% 7/9 • 2 years
Gastrointestinal disorders Upper gastrointestinal hemorrhage	11.1% 1/9 • 2 years
Infections and infestations Upper respiratory infection	11.1% 1/9 • 2 years
Investigations White blood cell decreased	77.8% 7/9 • 2 years

Other adverse events

Other adverse events
Measure	Cyclophosphamide, Topotecan, and Bevacizumab (CTB) n=9 participants at risk This is a multi-center, open label phase II study evaluating the safety and efficacy of the novel combination of agents consisting of bevacizumab, cyclophosphamide, and topotecan. Cyclophosphamide, Topotecan, and Bevacizumab: The treatment schedule for this study will consist of a 21-day cycle. Dose modification will only occur with administration of the investigational agent, bevacizumab. The schedule of administration is summarized as follows. Administration of bevacizumab will precede the administration of the cyclophosphamide and topotecan by 3 days (Day - 3) to allow for vascular stabilization prior to initiation of chemotherapy. The chemotherapy backbone will consist of cyclophosphamide and topotecan administered as follows: cyclophosphamide 250 mg/m2/day IV over 30 minutes ± 5 minutes on Days 0-4 followed by topotecan 0.75 mg/m2/day IV over 30 minutes ± 5 minutes on Day 0-4 of every cycle. The dosing of cyclophosphamide and topotecan will be fixed.
Blood and lymphatic system disorders Anemia	77.8% 7/9 • 2 years
Investigations Lymphocyte count decreased	77.8% 7/9 • 2 years
Investigations Neutrophil count decreased	77.8% 7/9 • 2 years
Investigations Platelet count decreased	77.8% 7/9 • 2 years
Investigations White blood cell decreased	77.8% 7/9 • 2 years
Gastrointestinal disorders Nausea	55.6% 5/9 • 2 years
Blood and lymphatic system disorders Febrile neutropenia	44.4% 4/9 • 2 years
Investigations Alanine aminotransferase increased	33.3% 3/9 • 2 years
Investigations Aspartate aminotransferase increased	33.3% 3/9 • 2 years
Gastrointestinal disorders Vomiting	33.3% 3/9 • 2 years
Gastrointestinal disorders Abdominal pain	22.2% 2/9 • 2 years
Metabolism and nutrition disorders Anorexia	22.2% 2/9 • 2 years
Gastrointestinal disorders Diarrhea	22.2% 2/9 • 2 years
General disorders Fatigue	22.2% 2/9 • 2 years
Gastrointestinal disorders Mucositis oral	22.2% 2/9 • 2 years
Investigations Alkaline phosphatase increased	11.1% 1/9 • 2 years
Skin and subcutaneous tissue disorders Alopecia	11.1% 1/9 • 2 years
Gastrointestinal disorders Constipation	11.1% 1/9 • 2 years
Renal and urinary disorders Cystitis noninfective	11.1% 1/9 • 2 years
Respiratory, thoracic and mediastinal disorders Epistaxis	11.1% 1/9 • 2 years
General disorders Fever	11.1% 1/9 • 2 years
Nervous system disorders Headache	11.1% 1/9 • 2 years
Renal and urinary disorders Hematuria	11.1% 1/9 • 2 years
Metabolism and nutrition disorders Hypernatremia	11.1% 1/9 • 2 years
Metabolism and nutrition disorders Hypoalbuminemia	11.1% 1/9 • 2 years
Metabolism and nutrition disorders Hypocalcemia	11.1% 1/9 • 2 years
Metabolism and nutrition disorders Hypokalemia	11.1% 1/9 • 2 years
Metabolism and nutrition disorders Metabolism and nutrition disorders-Other	11.1% 1/9 • 2 years
Gastrointestinal disorders Oral pain	11.1% 1/9 • 2 years
General disorders Pain	11.1% 1/9 • 2 years
Gastrointestinal disorders Proctitis	11.1% 1/9 • 2 years
Gastrointestinal disorders Upper gastrointestinal hemorrhage	11.1% 1/9 • 2 years

Additional Information

Dr. Tanya Trippett, MD

Memorial Sloan Kettering Cancer Center

Phone: 212-639-8267

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place