Aflibercept in Treating Young Patients With Relapsed or Refractory Solid Tumors

• Register: ClinicalTrials.gov
• Last refreshed on: 19 February 2015
• Main ID: NCT00622414
• Date of registration: 22/02/2008
• Prospective Registration: Yes
• Primary sponsor: National Cancer Institute (NCI)
• Public title: Aflibercept in Treating Young Patients With Relapsed or Refractory Solid Tumors
• Scientific title: A Phase I Study of VEGF Trap (NSC# 724770, IND# 100137) in Children With Refractory Solid Tumors
• Date of first enrolment: April 2008
• Target sample size: 27
• Recruitment status: Completed
• URL: http://clinicaltrials.gov/show/NCT00622414
• Study type: Interventional
• Study design: Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
• Phase: Phase 1

Countries of recruitment

Canada, United States

Contacts

• Name: Julie Park
• Affiliation: COG Phase I Consortium

Key inclusion & exclusion criteria

Inclusion Criteria:

- Histologically confirmed malignancy at original diagnosis or relapse (excluding
intrinsic brain stem tumors, optic pathway gliomas, or patients with pineal tumors
and elevations of serum alpha-fetoprotein of beta-HCG)

- Patients with recurrent or refractory solid tumors are eligible, including
primary CNS tumors or patients with known CNS metastases

- Current disease state must be one for which there is no known curative therapy or
therapy proven to prolong survival with an acceptable quality of life

- Measurable or evaluable disease

- No evidence of CNS hemorrhage on baseline MRI for patients with known CNS disease

- Karnofsky performance status (PS) 50-100% (for patients > 10 years of age) or Lansky
PS 50-100% (for patients = 10 years of age)

- Neurologic deficits in patients with CNS tumors must have been relatively stable
for a minimum of 1 week prior to study entry

- Patients who are unable to walk because of paralysis, but who are up in a
wheelchair, will be considered ambulatory for the purpose of assessing the
performance score

- Patients with solid tumors without bone marrow involvement must meet the following
criteria:

- ANC = 1,000/mm³

- Platelet count = 100,000/mm³ (transfusion independent, defined as not receiving
platelet transfusions within a 7 day period prior to enrollment)

- Hemoglobin = 8.0 g/dL (may receive RBC transfusions)

- Negative protein dipstick OR urine protein < 500 mg by 24-hour urine collection

- Creatinine clearance or radioisotope glomerular filtration rate = 70 mL/min OR serum
creatinine based on age/gender as follows:

- 0.6 mg/dL for male and female patients 1 to < 2 years of age

- 0.8 mg/dL for male and female patients 2 to < 6 years of age

- 1.0 mg/dL for male and female patients 6 to < 10 years of age

- 1.2 mg/dL for male and female patients 10 to < 13 years of age

- 1.5 mg/dL (male) or 1.4 mg/dL (female) for patients 13 to < 16 years of age

- 1.7 mg/dL (male) or 1.4 mg/dL (female) for patients = 16 years of age

- Bilirubin = 1.5 times upper limit of normal (U.N.) for age

- SEPT (ALT) = 110 µ/L (approx. 2.5 times U.N.) (for the purpose of this study, the
U.N. for SEPT is 45 µ/L)

- Serum albumin = 2 g/dL

- PT/aPTT < 1.2 times U.N.

- Patients must have a diastolic blood pressure = the 95th percentile for age and
gender and not be receiving treatment for hypertension

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No evidence of active graft-vs-host disease

- No uncontrolled infection

- No serious or nonhealing wound, ulcer, or bone fracture

- No history of abdominal fistula, gastrointestinal perforation, or intra-abdominal
abscess within 4 weeks prior to day 1 of study treatment

- No clinically significant cardiovascular disease within the past 6 months, including
any of the following:

- History of cerebrovascular accident

- New York Heart Association class III-IV congestive heart failure

- Serious cardiac arrhythmia requiring medication

- Unstable angina pectoris

- Pulmonary embolism

- Deep vein thrombosis

- Other thromboembolic events

- No evidence of a current bleeding diathesis or coagulopathy

- No known hypersensitivity to Chinese hamster ovary cell products or other recombinant
human antibodies

- No history of allergic reactions attributed to compounds of similar chemical or
biologic composition to other agents used in the study

- No significant traumatic injury within 4 weeks prior to day 1 of study treatment

- Must be able to comply with the safety monitoring requirements of the study in the
opinion of the investigator

- Recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or
radiotherapy

- No prior aflibercept

- At least 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosourea)

- At least 6 weeks since prior monoclonal antibodies

- At least 2 weeks since prior local palliative radiotherapy (small port)

- At least 6 weeks since other prior substantial bone marrow radiotherapy

- At least 2 months since prior stem cell transplantation or rescue

- At least 3 months since prior total-body irradiation, craniospinal radiotherapy, or
radiotherapy to = 50% of the pelvis

- At least 4 weeks since prior major surgical procedure, laparoscopic procedure, or
open biopsy and no anticipation of need for major surgical procedures during the
course of the study

- At least 48 hours since prior fine needle aspirate, central line placement, or
subcutaneous port placement

- At least 1 week since prior core biopsy

- At least 1 week since prior and no concurrent hematopoietic growth factors

- At least 1 week since prior and no concurrent biologic agents

- At least 1 week since prior and no concurrent dexamethasone

- No concurrent antihypertensive medications for blood pressure control

- No concurrent anti-thrombotic or anti-platelet agents (e.g., warfarin [Coumadin
®],heparin, low molecular weight heparin, aspirin, and/or ibuprofen, or other NSAIDs)

- No concurrent medications known to inhibit platelet function or known to selectively
inhibit cyclooxygenase-2 activity (e.g., all antipyretic and anti-inflammatory
medications except acetaminophen)

- No other concurrent anticancer therapy, including chemotherapy, radiotherapy,
immunotherapy, or biologic therapy

- No other concurrent investigational drugs



Age minimum: 1 Year
Age maximum: 21 Years
Gender: Both

Health Condition(s) or Problem(s) studied

Unspecified Childhood Solid Tumor, Protocol Specific

Intervention(s)

Biological: ziv-aflibercept

Primary Outcome(s)

Maximum tolerated dose, defined as the maximum dose at which fewer than one-third of patients experience DLT during the initial 2 courses of therapy, graded according to NCI CTCAE version 3.0 [Time Frame: Up to 28 days]

Secondary ID(s)

COG-ADVL0714

NCI-08-C-0179

NCI-2009-01062

ADVL0714

NCI-P08401

CDR0000584050

U01CA097452

Source(s) of Monetary Support

Please refer to primary and secondary sponsors