A Study of Vincristine, Escalating Doses of Irinotecan, T... | NCT00993044

Status Module

Oversight Module

Arms/Interventions Module

Label	Type	Description	Intervention Names
Single Arm	Experimental		Drug: Irinotecan Drug: Vincristine Drug: Temozolomide Drug: Bevacizumab

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Irinotecan	Drug	Dose Level 1 Irinotecan 30 mg/m2/day IV on day 1,2,3,4 and 5 Vincristine 1.5mg/m2 (2mg max dose) IV on day 1,8 Temozolomide 100 mg/m2 PO on day 1,2,3,4 and 5 Bevacizumab 15mg/kg IV on day 1 Dose Level 1.5* Irinotecan 40 mg/m2/day IV on day 1,2,3,4 and 5 Vincristine 1.5mg/m2 (2mg max dose) IV on day 1,8 Temozolomide 100 mg/m2 PO on day 1,2,3,4 and 5 Bevacizumab 15mg/kg IV on day 1 Dose Level 2 Irinotecan 50 mg/m2/day IV on day 1,2,3,4 and 5 Vincristine 1.5mg/m2 (2mg max dose) IV on day 1,8 Temozolomide 100 mg/m2 PO on day 1,2,3,4 and 5 Bevacizumab 15mg/kg IV on day 1 Dose Level -1 Irinotecan 20 mg/m2/day IV on day 1,2,3,4 and 5 Vincristine 1.5mg/m2 (2mg max dose) IV on day 1,8 Temozolomide 100 mg/m2 PO on day 1,2,3,4 and 5 Bevacizumab 15mg/kg IV on day 1 * Dose escalation will proceed from dose level 1 to dose level 2 and de-escalate to dose level 1.5 if DLT is observed on dose level 2

Measure	Description	Time Frame
Dose Limiting Toxicity	Number of participants with dose limiting toxicity events	2 years

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Age: Patients must be > 12 months and < 21 years of age at the time of study entry.
Weight: Patient must be more than or equal to 10 Kilograms.

Histological Diagnosis:

Patients must have had histological verification of the malignancy at some time prior to study entry.
All solid tumors are eligible with the exclusion of lymphomas. For patients with neuroblastoma, diagnosis based on elevated catecholamines in the urine and tumor cells on bone marrow aspirates/biopsies is acceptable.
For patients with germ cell tumors, diagnosis based on elevated tumor markers (serum alpha fetoprotein and/or serum beta human chorionic gonadotropin) and radiographic evidence of disease is acceptable.

Disease Status:

Disease must have failed standard therapy (therapies) or be a disease for which no standard therapy exists.
Patient with stable disease on other therapies are not eligible.

Performance Level:

Karnofsky > 50% for patients >16 years of age and Lansky > 50 for children < 16 years of age (Appendix I).
Life Expectancy: Must be > 8 weeks.

Exclusion Criteria:

Patients who have received bevacizumab and/or Irinotecan previously are ineligible. Non brain tumor patients who have previously received Temozolomide are ineligible.
Pregnancy or Breast-Feeding: Pregnant patients are ineligible for this study due to the known teratogenic effects of the cytotoxic agents. Pregnancy tests must be obtained in females of childbearing potential prior to enrollment.
Lactating women must agree not to breast-feed.
Males or females of reproductive age may not participate unless they have agreed to use an effective contraceptive method.
Patients Who Have an Uncontrolled Infection will not be eligible for enrollment until all infections are under control.
Clinically Significant Unrelated Systemic Illness: Patients with serious infections or significant pulmonary, hepatic, renal, or other end-organ dysfunction which in the judgment of the Principal or Co-Investigators would compromise the patient's ability to tolerate prescribed chemotherapy or are likely to interfere with the study procedures or results will not be eligible.

Name	Affiliation	Role
Rajkumar Venkatramani, MD	Children's Hospital Los Angeles	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Childrens Hospital los Angeles		Los Angeles	California	90027	United States

PubMed Identifier	Type	Citation	Retractions
23894304	Result	Venkatramani R, Malogolowkin M, Davidson TB, May W, Sposto R, Mascarenhas L. A phase I study of vincristine, irinotecan, temozolomide and bevacizumab (vitb) in pediatric patients with relapsed solid tumors. PLoS One. 2013 Jul 22;8(7):e68416. doi: 10.1371/journal.pone.0068416. Print 2013.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Single Arm	combination of Irinotecan, vincristine, temozolomide and bevacizumab: Vincristine 1.5mg/m2 (2mg max dose) IV on day 1,8 Temozolomide 100 mg/m2 PO on day 1,2,3,4 and 5 Bevacizumab 15mg/kg IV on day 1 Dose Level 1 Irinotecan 30 mg/m2/day IV on day 1,2,3,4 and 5 Dose Level 1.5* Irinotecan 40 mg/m2/day IV on day 1,2,3,4 and 5 Dose Level 2 Irinotecan 50 mg/m2/day IV on day 1,2,3,4 and 5 Dose Level -1 Irinotecan 20 mg/m2/day IV on day 1,2,3,4 and 5 * Dose escalation will proceed from dose level 1 to dose level 2 and de-escalate to dose level 1.5 if DLT is observed

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

ID	Title	Description
BG000	Dose Level 1, 2

Units	Counts
Participants	BG00012

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Median

Full Range

Years

Title

Denominators

Categories

Title	Measurements
	BG00011(3.9 to 19.4)

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG0004
Male	BG0008

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000
Asian	BG0000

Region of Enrollment

Number

participants

Title

Denominators

Categories

United States

Title	Measurements
	BG00012

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Dose Limiting Toxicity

Number of participants with dose limiting toxicity events

Posted

Number

participants

2 years

ID	Title	Description
OG000	Single Arm	combination of Irinotecan, vincristine, temozolomide and bevacizumab: Vincristine 1.5mg/m2 (2mg max dose) IV on day 1,8 Temozolomide 100 mg/m2 PO on day 1,2,3,4 and 5 Bevacizumab 15mg/kg IV on day 1 Dose Level 1 Irinotecan 30 mg/m2/day IV on day 1,2,3,4 and 5 Dose Level 1.5* Irinotecan 40 mg/m2/day IV on day 1,2,3,4 and 5 Dose Level 2 Irinotecan 50 mg/m2/day IV on day 1,2,3,4 and 5 Dose Level -1 Irinotecan 20 mg/m2/day IV on day 1,2,3,4 and 5 * Dose escalation will proceed from dose level 1 to dose level 2 and de-escalate to dose level 1.5 if DLT is observed

Units	Counts
Participants	OG00012

Title

Denominators

Categories

Title	Measurements
	OG0002

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Dose Level 1	combination of Irinotecan, vincristine, temozolomide and bevacizumab: Vincristine 1.5mg/m2 (2mg max dose) IV on day 1,8 Temozolomide 100 mg/m2 PO on day 1,2,3,4 and 5 Bevacizumab 15mg/kg IV on day 1 Dose Level 1 Irinotecan 30 mg/m2/day IV on day 1,2,3,4 and 5			1	6	6	6
EG001	Dose Level 2	combination of Irinotecan, vincristine, temozolomide and bevacizumab: Vincristine 1.5mg/m2 (2mg max dose) IV on day 1,8 Temozolomide 100 mg/m2 PO on day 1,2,3,4 and 5 Bevacizumab 15mg/kg IV on day 1 Dose Level 2 Irinotecan 50 mg/m2/day IV on day 1,2,3,4 and 5			1	6	6	6

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Hyperbilirubinemia	Hepatobiliary disorders		Systematic Assessment	The first patient enrolled on dose level 1 had Noonan syndrome and recurrent synovial sarcoma.	EG0001 events1 affected6 at risk EG0010 affected6 at risk
colitis	Gastrointestinal disorders		Systematic Assessment		EG0000 affected6 at risk EG0011 events1 affected6 at risk

Term	Organ System	Assessment Type	Statistical Information
Anemia	Blood and lymphatic system disorders	Systematic Assessment	EG0006 affected6 at risk EG0016 affected6 at risk
Thrombocytopenia	Blood and lymphatic system disorders	Non-systematic Assessment	EG0006 affected6 at risk EG0016 affected6 at risk
Neutropenia	Blood and lymphatic system disorders	Non-systematic Assessment	EG0006 affected6 at risk EG0016 affected6 at risk

Title	Organization	Phone	Extension	Email
Rajkumar Venkatramani	Children's Hospital Los Angeles	3233615504		rvenkatramani@chla.usc.edu

ID	Term
D000077146	Irinotecan
D014750	Vincristine
D000077204	Temozolomide
D000068258	Bevacizumab

Ancestor Terms

ID	Term
D002166	Camptothecin
D000470	Alkaloids
D006571	Heterocyclic Compounds
D014748	Vinca Alkaloids
D046948	Secologanin Tryptamine Alkaloids
D026121	Indole Alkaloids
D007211	Indoles
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D054836	Indolizidines
D007212	Indolizines
D003606	Dacarbazine
D014226	Triazenes
D009930	Organic Chemicals
D007093	Imidazoles
D001393	Azoles
D006573	Heterocyclic Compounds, 1-Ring
D061067	Antibodies, Monoclonal, Humanized
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins
D007162	Immunoproteins
D001798	Blood Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D012712	Serum Globulins
D005916	Globulins