Bevacizumab in Treating Young Patients With Refractory Solid Tumors

Sponsor

National Cancer Institute (NCI) (NIH)

Overall Status

Completed

CT.gov ID

NCT00085111

Collaborator

(none)

Enrollment

Location

Arm

Study Details

Study Description

Brief Summary

This phase I trial is studying the side effects and best dose of bevacizumab in treating young patients with refractory solid tumors. Monoclonal antibodies, such as bevacizumab, can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells.

Condition or Disease	Intervention/Treatment	Phase
Unspecified Childhood Solid Tumor, Protocol Specific	Biological: bevacizumab	Phase 1

Detailed Description

PRIMARY OBJECTIVES:

To estimate the maximum tolerable dose (MTD) of bevacizumab by dose escalation to a maximum of 15mg/kg, even if MTD is not reached, administered as an intravenous infusion, every 2 weeks to children with refractory solid tumors.
To determine the dose-limiting toxicities (DLT) and other toxicities of bevacizumab given on this schedule.
To characterize the pharmacokinetic behavior of bevacizumab in children with refractory cancer.

SECONDARY OBJECTIVES:

To preliminarily define the antitumor activity of bevacizumab within the confines of a phase I study.
To assess the biologic activity of bevacizumab by measuring levels of total serum VEGF, and parallel angiogenic markers V-CAM-1, ICAM-1, bFGF, and TSP-1 at baseline and at time points post therapy.
To explore the biologic effect of bevacizumab on circulating endothelial cells (CECs) and circulating endothelial cell precursors (CECPs).
To determine in archival tumor tissue the expression of VEGF by immunohistochemistry and/or real time PCR.

OUTLINE: This is a dose-escalation, multicenter study.

Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of bevacizumab until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Study Design

Study Type:

Interventional

Actual Enrollment :

24 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase I Study of Bevacizumab in Refractory Solid Tumors

Study Start Date :

Dec 1, 2003

Actual Primary Completion Date :

Oct 1, 2005

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.	Biological: bevacizumab Given IV Other Names: anti-VEGF humanized monoclonal antibody anti-VEGF monoclonal antibody Avastin rhuMAb VEGF

Arm

Intervention/Treatment

Experimental: Arm I

Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.

Biological: bevacizumab

Given IV

Other Names:

anti-VEGF humanized monoclonal antibody

anti-VEGF monoclonal antibody

Avastin

rhuMAb VEGF

Outcome Measures

Primary Outcome Measures

Maximum tolerated dose defined based on the dose-limiting toxicities graded according to Common Terminology Criteria for Adverse Events v3.0 [28 days]

Eligibility Criteria

Criteria

Ages Eligible for Study:

1 Year to 21 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologically confirmed solid tumor at original diagnosis
Measurable or evaluable* disease
No known curative therapy exists
No lymphomas or primary CNS tumors
No history or clinical evidence of CNS metastasis by head CT scan
Performance status - Karnofsky 50-100% (patients > 10 years of age)
Performance status - Lansky 50-100% (patients ≤ 10 years of age)
At least 8 weeks
Patients without bone marrow involvement:
Absolute neutrophil count ≥ 1,000/mm^3
Platelet count ≥ 100,000/mm^3 (transfusion independent)
Hemoglobin ≥ 8.0 g/dL (RBC transfusion allowed)
Patients with bone marrow metastases:
Platelet count ≥ 75,000/mm^3 (transfusion independent)
Granulocytopenia, anemia, and/or mild thrombocytopenia allowed
No known bleeding diathesis or coagulopathy
No known thrombophilic condition (e.g., protein S, protein C, or antithrombin III deficiency, Factor V Leiden, Factor II G20210A mutation, homocystinemia, or antiphospholipid antibody syndrome)
PT or PTT ≤ 1.2 times upper limit of normal (ULN)
ALT ≤ 5 times ULN
Bilirubin ≤ 1.5 times ULN
Albumin ≥ 2 g/dL
Creatinine clearance or radioisotope glomerular filtrationrate ≥ 70 mL/min
Creatinine based on age as follows:
Creatinine ≤ 0.8 mg/dL (patients ≤ 5 years of age)
Creatinine ≤ 1.0 mg/dL (patients 6 to 10 years of age)
Creatinine ≤ 1.2 mg/dL (patients 11 to 15 years of age)
Creatinine ≤ 1.5 mg/dL (patients > 15 years of age)
No proteinuria
24-hour urine protein ≤ 500 mg
No history of stroke
No deep venous or arterial thrombosis within the past 3 months
No uncontrolled hypertension
Hypertension must be well-controlled with stable doses of medication for at least 2 weeks
No history of myocardial infarction
No severe or unstable angina
No transient ischemic attack within the past 6 months
No cerebrovascular accident within the past 6 months
No other arterial thromboembolic event within the past 6 months
No clinically significant or severe peripheral vascular disease
No pulmonary embolism within the past 3 months
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for at least 3 months after study participation
No chronic non-healing wound, ulcer, or bone fracture
No significant traumatic injury within the past 28 days
No uncontrolled seizures
No uncontrolled infection
No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
Recovered from prior immunotherapy
More than 1 week since prior growth factors
At least 2 months since prior stem cell transplantation
No evidence of active graft-vs-host disease
At least 8 weeks since prior monoclonal antibody therapy
At least 7 days since prior antineoplastic biologic agents
No prior bevacizumab
No concurrent prophylactic growth factors
No other concurrent immunotherapy or biologic therapy
More than 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosoureas) and recovered
No concurrent chemotherapy
Recovered from prior radiotherapy
At least 4 months since prior craniospinal radiotherapy
At least 4 months since prior radiotherapy to ≥ 50% of the pelvis
At least 6 weeks since other prior substantial bone marrow radiotherapy
At least 2 weeks since prior local palliative small-port radiotherapy
No concurrent radiotherapy
More than 28 days since prior major surgery
At least 7 days since prior minor surgery (for limited purposes of tissue retrieval) and recovered
At least 24 hours since prior placement of an indwelling IV catheter
At least 1 week since prior full-dose anticoagulation therapy, including systemic thrombolytic agents, heparin, low-molecular weight heparin, and warfarin
Local intralumenal anticoagulants (e.g., heparin or tissue plasminogen activator) allowed to maintain patency of preexisting, permanent, indwelling IV catheters or peripheral IV catheters for blood sampling
More than 1 week since prior antipyretic and anti-inflammatory medications (except acetaminophen)
No concurrent full-dose anticoagulation therapy
No concurrent anti-inflammatory medication
Concurrent acetaminophen allowed
No other concurrent cancer therapy
No other concurrent investigational agents