Trial Outcomes & Findings for Vincristine Sulfate, Topotecan Hydrochloride, and Cyclophosphamide With or Without Bevacizumab in Treating Young Patients With Refractory or First Recurrent Extracranial Ewing Sarcoma (NCT NCT00516295)

Last Updated: 2014-09-02

Results Overview

Limiting toxicity defined as Any Grade IV hematological toxicities lasting longer than 7 days, myelosuppression causing delays \> 14 days in delivery of therapy, \> Grade 3 thromboembolic events, \> Grade 3 bleeding events, \> Grade 2 hypertension, \> Grade 2 proteinuria.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

7 participants

Primary outcome timeframe

First 2 courses (42 days) of therapy

Results posted on

2014-09-02

Participant Flow

Participant milestones

Participant milestones
Measure	Arm I (Feasibility Assessment of VTCB) Patients receive bevacizumab IV over 30-90 minutes on day 1, vincristine sulfate IV on days 1, 8, and 15, and topotecan hydrochloride IV over 30 minutes and cyclophosphamide IV over 60 minutes on days 1-5. Treatment repeats every 21 days (except during weeks 14, 15 \[course 5\], 17, 18 \[course 6\], 26, 27 \[course 9\], 29, and 30 \[course 10\] when no chemotherapy is given) for up to 12 courses in the absence of disease progression or unacceptable toxicity. topotecan hydrochloride: Given IV vincristine sulfate: Given IV cyclophosphamide: Given IV bevacizumab: Given IV	Arm II (VTCB) Patients receive bevacizumab, vincristine sulfate, topotecan hydrochloride, and cyclophosphamide as in Arm I.	Arm III (CTC) Patients receive vincristine, topotecan hydrochloride, and cyclophosphamide as in arm I.
Overall Study STARTED	7	0	0
Overall Study COMPLETED	4	0	0
Overall Study NOT COMPLETED	3	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm I (Feasibility Assessment of VTCB) Patients receive bevacizumab IV over 30-90 minutes on day 1, vincristine sulfate IV on days 1, 8, and 15, and topotecan hydrochloride IV over 30 minutes and cyclophosphamide IV over 60 minutes on days 1-5. Treatment repeats every 21 days (except during weeks 14, 15 \[course 5\], 17, 18 \[course 6\], 26, 27 \[course 9\], 29, and 30 \[course 10\] when no chemotherapy is given) for up to 12 courses in the absence of disease progression or unacceptable toxicity. topotecan hydrochloride: Given IV vincristine sulfate: Given IV cyclophosphamide: Given IV bevacizumab: Given IV	Arm II (VTCB) Patients receive bevacizumab, vincristine sulfate, topotecan hydrochloride, and cyclophosphamide as in Arm I.	Arm III (CTC) Patients receive vincristine, topotecan hydrochloride, and cyclophosphamide as in arm I.
Overall Study Lack of Efficacy	2	0	0
Overall Study Ineligible	1	0	0

Baseline Characteristics

Vincristine Sulfate, Topotecan Hydrochloride, and Cyclophosphamide With or Without Bevacizumab in Treating Young Patients With Refractory or First Recurrent Extracranial Ewing Sarcoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm I (Feasibility Assessment of VTCB) n=7 Participants Patients receive bevacizumab IV over 30-90 minutes on day 1, vincristine sulfate IV on days 1, 8, and 15, and topotecan hydrochloride IV over 30 minutes and cyclophosphamide IV over 60 minutes on days 1-5. Treatment repeats every 21 days (except during weeks 14, 15 \[course 5\], 17, 18 \[course 6\], 26, 27 \[course 9\], 29, and 30 \[course 10\] when no chemotherapy is given) for up to 12 courses in the absence of disease progression or unacceptable toxicity. topotecan hydrochloride: Given IV vincristine sulfate: Given IV cyclophosphamide: Given IV bevacizumab: Given IV	Arm II (VTCB) Patients receive bevacizumab, vincristine sulfate, topotecan hydrochloride, and cyclophosphamide as in Arm I	Arm III (VTC) Patients receive vincristine sulfate, topotecan hydrochloride, and cyclophosphamide as in arm I.	Total n=7 Participants Total of all reporting groups
Age, Continuous	15 years n=5 Participants	—	—	15 years n=4 Participants
Gender Female	2 participants n=5 Participants	—	—	2 participants n=4 Participants
Gender Male	5 participants n=5 Participants	—	—	5 participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 participants n=5 Participants	—	—	0 participants n=4 Participants
Race (NIH/OMB) Asian	0 participants n=5 Participants	—	—	0 participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 participants n=5 Participants	—	—	0 participants n=4 Participants
Race (NIH/OMB) Black or African American	0 participants n=5 Participants	—	—	0 participants n=4 Participants
Race (NIH/OMB) White	6 participants n=5 Participants	—	—	6 participants n=4 Participants
Race (NIH/OMB) More than one race	0 participants n=5 Participants	—	—	0 participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	1 participants n=5 Participants	—	—	1 participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 participants n=5 Participants	—	—	2 participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	5 participants n=5 Participants	—	—	5 participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 participants n=5 Participants	—	—	0 participants n=4 Participants
Region of Enrollment United States	7 participants n=5 Participants	—	—	7 participants n=4 Participants

PRIMARY outcome

Timeframe: First 2 courses (42 days) of therapy

Population: Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.

Outcome measures

Outcome measures
Measure	Arm I (Feasibility Assessment of VTCB) n=6 Participants Patients receive bevacizumab IV over 30-90 minutes on day 1, vincristine sulfate IV on days 1, 8, and 15, and topotecan hydrochloride IV over 30 minutes and cyclophosphamide IV over 60 minutes on days 1-5. Treatment repeats every 21 days (except during weeks 14, 15 \[course 5\], 17, 18 \[course 6\], 26, 27 \[course 9\], 29, and 30 \[course 10\] when no chemotherapy is given) for up to 12 courses in the absence of disease progression or unacceptable toxicity. topotecan hydrochloride: Given IV vincristine sulfate: Given IV cyclophosphamide: Given IV bevacizumab: Given IV	Arm II (VTCB) Patients receive bevacizumab, vincristine sulfate, topotecan hydrochloride, and cyclophosphamide as in Arm I.	Arm III (VTC) Patients receive vincristine sulfate, topotecan hydrochloride, and cyclophosphamide as in arm I.
The Occurrence of Limiting Toxicity in an Eligible and Evaluable Patient.	0 number of toxicities	—	—

PRIMARY outcome

Timeframe: Maximum of 5 years after enrollment

Population: Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.

Time from enrollment to disease progression, death, second malignant neoplasm, or last patient follow-up whichever occurs first. Patients who experience disease progression, death or second malignant neoplasm will be considered to have experienced an event; otherwise the patient will be considered censored at last follow-up.

Outcome measures

Outcome measures
Measure	Arm I (Feasibility Assessment of VTCB) n=6 Participants Patients receive bevacizumab IV over 30-90 minutes on day 1, vincristine sulfate IV on days 1, 8, and 15, and topotecan hydrochloride IV over 30 minutes and cyclophosphamide IV over 60 minutes on days 1-5. Treatment repeats every 21 days (except during weeks 14, 15 \[course 5\], 17, 18 \[course 6\], 26, 27 \[course 9\], 29, and 30 \[course 10\] when no chemotherapy is given) for up to 12 courses in the absence of disease progression or unacceptable toxicity. topotecan hydrochloride: Given IV vincristine sulfate: Given IV cyclophosphamide: Given IV bevacizumab: Given IV	Arm II (VTCB) Patients receive bevacizumab, vincristine sulfate, topotecan hydrochloride, and cyclophosphamide as in Arm I.	Arm III (VTC) Patients receive vincristine sulfate, topotecan hydrochloride, and cyclophosphamide as in arm I.
Time to Disease Progression in Patients Receiving VTC With or Without Bevacizumab	442 days of event free survival Interval 42.0 to There is no numerical limit available because the limit is infinity.	—	—

Adverse Events

Arm I (Feasibility Assessment of VTCB)

Serious events: 5 serious events

Other events: 6 other events

Deaths: 0 deaths

Arm II (VTCB)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Arm III (VTC)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Arm I (Feasibility Assessment of VTCB) n=6 participants at risk Patients receive bevacizumab IV over 30-90 minutes on day 1, vincristine sulfate IV on days 1, 8, and 15, and topotecan hydrochloride IV over 30 minutes and cyclophosphamide IV over 60 minutes on days 1-5. Treatment repeats every 21 days (except during weeks 14, 15 \[course 5\], 17, 18 \[course 6\], 26, 27 \[course 9\], 29, and 30 \[course 10\] when no chemotherapy is given) for up to 12 courses in the absence of disease progression or unacceptable toxicity. topotecan hydrochloride: Given IV vincristine sulfate: Given IV cyclophosphamide: Given IV bevacizumab: Given IV	Arm II (VTCB) Patients receive bevacizumab, vincristine sulfate, topotecan hydrochloride, and cyclophosphamide as in Arm I.	Arm III (VTC) Patients receive vincristine sulfate, topotecan hydrochloride, and cyclophosphamide as in arm I.
Injury, poisoning and procedural complications Burn	16.7% 1/6 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.	— 0/0 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.	— 0/0 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.
Gastrointestinal disorders Esophageal stenosis	16.7% 1/6 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.	— 0/0 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.	— 0/0 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.
Blood and lymphatic system disorders Febrile neutropenia	66.7% 4/6 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.	— 0/0 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.	— 0/0 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.
Infections and infestations Infections and infestations - Other, specify	66.7% 4/6 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.	— 0/0 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.	— 0/0 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.
Investigations Platelet count decreased	16.7% 1/6 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.	— 0/0 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.	— 0/0 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.
Gastrointestinal disorders Vomiting	16.7% 1/6 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.	— 0/0 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.	— 0/0 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.

Other adverse events

Additional Information

Results Reporting Coordinator

Children's Oncology Group

Phone: 626-447-0064

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Measure	Arm I (Feasibility Assessment of VTCB) n=6 participants at risk Patients receive bevacizumab IV over 30-90 minutes on day 1, vincristine sulfate IV on days 1, 8, and 15, and topotecan hydrochloride IV over 30 minutes and cyclophosphamide IV over 60 minutes on days 1-5. Treatment repeats every 21 days (except during weeks 14, 15 \[course 5\], 17, 18 \[course 6\], 26, 27 \[course 9\], 29, and 30 \[course 10\] when no chemotherapy is given) for up to 12 courses in the absence of disease progression or unacceptable toxicity. topotecan hydrochloride: Given IV vincristine sulfate: Given IV cyclophosphamide: Given IV bevacizumab: Given IV	Arm II (VTCB) Patients receive bevacizumab, vincristine sulfate, topotecan hydrochloride, and cyclophosphamide as in Arm I.	Arm III (VTC) Patients receive vincristine sulfate, topotecan hydrochloride, and cyclophosphamide as in arm I.
Gastrointestinal disorders Abdominal pain	16.7% 1/6 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.	— 0/0 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.	— 0/0 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.
Investigations Alanine aminotransferase increased	16.7% 1/6 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.	— 0/0 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.	— 0/0 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.
Immune system disorders Allergic reaction	16.7% 1/6 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.	— 0/0 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.	— 0/0 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.
Blood and lymphatic system disorders Anemia	100.0% 6/6 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.	— 0/0 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.	— 0/0 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.
Metabolism and nutrition disorders Anorexia	33.3% 2/6 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.	— 0/0 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.	— 0/0 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.
Musculoskeletal and connective tissue disorders Arthralgia	16.7% 1/6 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.	— 0/0 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.	— 0/0 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.
Investigations Aspartate aminotransferase increased	16.7% 1/6 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.	— 0/0 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.	— 0/0 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.
Musculoskeletal and connective tissue disorders Back pain	16.7% 1/6 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.	— 0/0 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.	— 0/0 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.
Musculoskeletal and connective tissue disorders Bone pain	16.7% 1/6 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.	— 0/0 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.	— 0/0 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.
Infections and infestations Catheter related infection	16.7% 1/6 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.	— 0/0 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.	— 0/0 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.
Investigations Creatinine increased	16.7% 1/6 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.	— 0/0 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.	— 0/0 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.
Skin and subcutaneous tissue disorders Dry skin	16.7% 1/6 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.	— 0/0 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.	— 0/0 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.
Nervous system disorders Dysgeusia	16.7% 1/6 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.	— 0/0 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.	— 0/0 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.
Respiratory, thoracic and mediastinal disorders Epistaxis	33.3% 2/6 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.	— 0/0 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.	— 0/0 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.
Infections and infestations Esophageal infection	16.7% 1/6 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.	— 0/0 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.	— 0/0 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.
Blood and lymphatic system disorders Febrile neutropenia	16.7% 1/6 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.	— 0/0 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.	— 0/0 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.
Gastrointestinal disorders Gastritis	16.7% 1/6 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.	— 0/0 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.	— 0/0 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.
Nervous system disorders Headache	16.7% 1/6 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.	— 0/0 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.	— 0/0 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.
Metabolism and nutrition disorders Hyperkalemia	16.7% 1/6 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.	— 0/0 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.	— 0/0 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.
Metabolism and nutrition disorders Hypoalbuminemia	16.7% 1/6 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.	— 0/0 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.	— 0/0 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.
Infections and infestations Infections and infestations - Other, specify	33.3% 2/6 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.	— 0/0 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.	— 0/0 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.
Investigations Lymphocyte count decreased	33.3% 2/6 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.	— 0/0 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.	— 0/0 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.
Ear and labyrinth disorders Middle ear inflammation	16.7% 1/6 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.	— 0/0 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.	— 0/0 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.
Gastrointestinal disorders Mucositis oral	33.3% 2/6 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.	— 0/0 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.	— 0/0 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.
Gastrointestinal disorders Nausea	16.7% 1/6 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.	— 0/0 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.	— 0/0 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.
Investigations Neutrophil count decreased	66.7% 4/6 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.	— 0/0 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.	— 0/0 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.
Gastrointestinal disorders Oral hemorrhage	16.7% 1/6 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.	— 0/0 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.	— 0/0 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.
Nervous system disorders Peripheral motor neuropathy	33.3% 2/6 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.	— 0/0 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.	— 0/0 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.
Investigations Platelet count decreased	66.7% 4/6 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.	— 0/0 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.	— 0/0 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.
Skin and subcutaneous tissue disorders Rash maculo-papular	16.7% 1/6 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.	— 0/0 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.	— 0/0 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.
Infections and infestations Upper respiratory infection	16.7% 1/6 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.	— 0/0 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.	— 0/0 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.
Investigations White blood cell decreased	50.0% 3/6 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.	— 0/0 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.	— 0/0 Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.