MDACC Study Summary 2005-0910

Study Summary
No. 2005-0910:.......Advanced Cancers......David S. Hong......Phase I Program

Study Summary Title



Study Summary Number:	2005-0910

Study Title:	Phase I Clinical Trial Evaluating The Toxicity, Pharmacokinetics And Biological Effect Of Intravenous Bevacizumab (Avastin™) In Combination With Escalating Doses Of Oral AZD2171 For Patients With Advanced Malignancies.

Physician

New Patient Referral



Name:	David S. Hong	Patients Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Dept:	Phase I Program	Referring MD Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Phone:	713-563-1930 Contact us about clinical trials

General Information



Disease Group:	Advanced Cancers	Supported By:	N/A

Phase of Study:	Phase I	Return Visit:	Patients will have a pre-study visit then will visit the clinic once a week for 12 weeks. There will be one off-study visit.

Treatment Agents:	AZD2171 Bevacizumab	Home Care:	Not applicable. Standard of care.

Treatment Loc:	Only at MDACC

Estimated Length of Stay in Houston:	Not applicable


Description/ Intervention:	Unavailable

Study Objectives / Outcomes

OBJECTIVES

Primary:
1. To evaluate the safety and toxicity profile of intravenous bevacizumab (avastin™) administered in combination with oral AZD2171 for patients with advanced malignancies.
2. To determine the pharmacokinetic profile of oral AZD2171 in combination with bevacizumab (avastin™) administered to patients with advanced malignancies.

Secondary:
1. To evaluate the serum concentrations of Nitric Oxide (NO) and Nitric oxide synthase (NOS) among patients treated with this regimen and to correlate with VEGF expression,
2. To determine changes in the tumor vasculature detected by DCE-MRI among patients treated with this combination of VEGF receptor blocking agents.
3. To evaluate the potential predictive role of angiogenesis molecular endpoints in malignant effusion samples.
4. To assess in a descriptive fashion the efficacy of the studied regimen.

Study Status Information



Study Activation / Registration Date:	05/25/2007

IRB Review and Approval Date:	12/06/2006

Study Type:	Phase I

Recruitment Status:	Closed

Projected Accrual:	N/A

Enrollment Eligibility

If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:

1) Patients must have histological confirmation of Solid Tumor or Lymphoma that is metastatic or unresectable. If assessing a single target lesion, histological confirmation of that particular lesion MUST be carried out.

2) Patients may have received an unlimited number of prior therapies. However, At least 4 weeks MUST have passed since the last chemotherapy to day 1 of registration (6 weeks for regimens containing nitrosoureas or Mitomycin C).

3) Age >/= 15 years

4) ECOG performance status </= 2 (Karnofsky >/= 60%).

5) Patients must have normal organ and marrow function as defined below: leukocytes >/= 3,000/mcL absolute neutrophil count >/=1,500/mcL; platelets >/= 100,000/mcL total bilirubin less than or equal to 2.0 mg/dL. (Does NOT apply to patients with Gilbert's Syndrome); AST(SGOT)/ALT(SGPT) </= 2.5 X institutional upper limit of normal (Patients with liver involvement will be allowed less than or equal to 5.0 X institutional upper normal limit); serum creatinine </= 2.0 mg/dL

6) Patients MUST have recovered from all treatment related toxicities to Grade 1 NCI CTC (v 4.0) in severity.

7) Patients must be willing and able to review, understand, and provide written consent before starting therapy.

8) Patients with stable brain metastasis (stable disease on one MRI assessment at least 4 weeks after completion of whole brain radiation, no evidence of progression on MRI assessment 4 weeks after stereotactic radiosurgery or complete surgical excision) will also be allowed to participate in this trial.

9) Patients with histologically proven intracranial glioblastoma, gliosarcoma or anaplastic astrocytoma will be eligible. Patients must have shown unequivocal radiographic evidence for tumor progression by MRI scan as defined by Section 11.6. A scan should be performed within 14 days prior to registration and on a steroid dose that has been stable for at least 5 days. If the steroid dose is increased between the date of imaging and registration, a new baseline MRI is required.

Exclusion Criteria:

1) Patients with squamous non-small cell lung carcinoma.

2) Serious or non-healing wound, ulcer or bone fracture.

3) History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 28 days of day 1 of registration.

4) Invasive procedures defined as follows: Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to Day 1 therapy; Anticipation of need for major surgical procedures during the course of the study; Core biopsy within 7 days prior to day 1 of registration.

5) Patients may not be receiving any other investigational agents.

6) Patients with bleeding diathesis (clinical bleeding, prothrombin time =/> 1.5 X upper institutional normal value, INR =/> 1.5, activated partial thromboplastin time aPTT =/> 1.5 X upper institutional normal value), active gastric or duodenal ulcer.

7) Uncontrolled systemic vascular hypertension (Systolic blood pressure > 140 mmHg, Diastolic Blood Pressure > 90 mmHg).

8) Urine protein should be screened by dipstick or urine analysis. For proteinuria > 1+ or urine protein:creatinine ratio > 1.0, 24-hour urine protein should be obtained and the level should be < 1000 mg for patient enrollment.

9) Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring parenterol antibiotics on Day 1.

10) Patients with clinically significant cardiovascular disease: History of CVA within 6 months; Myocardial Infarction or unstable angina within 6 months; New York Heart Association Grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication, unstable angina pectoris; Clinically significant peripheral vascular disease: QTc prolongation >500msec or other significant ECG abnormality noted within 14 days of registration; Conditions requiring concurrent use of drugs or biologics with proarrythmic potential.

11) Pregnant women are excluded from this study because AZD-2171 is an angiogenesis inhibiting agent with potential teratogenic or abortifacient effects. Because of the potential risk for adverse events in nursing infants secondary to treatment of the mother with AZD-2171, breastfeeding should be discontinued if the mother is treated with AZD-2171.These potential risks may also apply to other agents used in this study. Women of child-bearing potential and men must agree to use contraception prior to study entry and for the duration of study participation.

12) (continued from exclusion criteria 11) Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.

Links

Registration Number: NCT00458731
Study Information on Clinical Trials Registry (clinicaltrials.gov)