Overview

Safety Study of Increasing Doses of Combretastatin in Combination With Bevacizumab (Avastin) in Patients With Advanced Solid Tumors

Status:
Completed
Trial end date:
2007-01-01
Target enrollment:
0
Participant gender:
All
Summary
The purpose of this study is to determine the safety and tolerability of three dose levels of combretastatin A4 phosphate (CA4P) given intravenously (IV) in combination with bevacizumab every 14 days in patients with advanced solid tumors. The maximum tolerated dose will be defined if it is at one of the three dose levels under study.
Phase:
Phase 1
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Mateon Therapeutics
Treatments:
Bevacizumab
Combretastatin
Fosbretabulin
Criteria
Inclusion Criteria:

1. Histopathologically or cytologically confirmed malignant solid tumors that have failed
standard therapy or for which no life prolonging treatment exists

2. Measurable disease as defined by the Response Evaluation Criteria in Solid Tumors
(RECIST) criteria

3. At least 4 weeks since any prior immunotherapy, chemotherapy or radiation therapy
prior to first dose of study drug (six weeks for therapy known to be associated with
delayed toxicity such as nitrosoureas or mitomycin-C)

4. Age > or = to 18 years old

5. Adequate bone marrow function:

1. absolute granulocyte count (neutrophils and bands) > or = to 1500 cells/mm3;

2. platelet count > or = to 100,000 cells/mm3;

3. hemoglobin > or = to 9 g/dL.

6. Adequate renal function (glomerular filtration calculated by Cockcroft/Gault formula
or measure urine creatinine clearance > or = to 50 mL/minute)

7. Adequate hepatic function:

1. bilirubin less than or = to 1.5 mg/dL;

2. aspartate transaminase (AST) and alanine transaminase (ALT) less than or = to 2.5
times the institutional upper limit of normal (ULN) (or less than or = to 5 times
ULN if liver metastases are present).

8. Eastern Cooperative Oncology Group (ECOG) performance status 0-2

9. Life expectancy of > or = to 12 weeks

10. Written, signed, dated, and witnessed (if applicable as per International Conference
on Harmonization [ICH] guidelines) Independent Ethics Committee (IEC) approved
informed consent form before any study specific screening procedures are performed

11. Fertile subjects must abstain from sexual intercourse or use effective birth control.

12. All women of child bearing potential (WOCBP) must have a negative serum pregnancy test
within 72 hours of first dose.

Exclusion Criteria:

1. Contraindications, allergies or sensitivity to the use of the study medications or any
other products required for participation in this study (i.e. contrast agents)

2. Presence of central nervous system (CNS) metastases

3. Diagnosed squamous non-small cell lung cancer (NSCLC)

4. History of gastrointestinal perforations

5. Surgery within 28 days of screening visit or a surgical incision that is not fully
healed. Any surgery planned during the study period.

6. Proteinuria >1 g/24 hours by 24 hour urine collection (perform 24 hour urine
collection if > 1+ on dipstick)

7. Recent hemoptysis (occurrence within the past 3 months)

8. Prior therapy with CA4P or bevacizumab, or other agents which target vascular
endothelial growth factor (VEGF) or VEGFR signaling such as Sorafenib and Sutent

9. Prior radiation involving > 30% of the bone marrow

10. Radical radiotherapy to the thorax or abdomen at any time or post-operative radical
radiotherapy to the pelvis. Palliative radiotherapy treatments are acceptable.
Subjects with rectal primaries who have received pre-operative pelvic radiotherapy or
chemoradiation are eligible if the small bowel was mobile and not stuck to the tumor.

11. Active autoimmune disorder(s)

12. Immunocompromised, including subjects known to be human immunodeficiency virus (HIV)
positive

13. Active infection requiring antibiotic therapy or any other serious intercurrent
illness

14. History of angina (stable or severe, even if controlled with medications), myocardial
infarction, congestive heart failure (CHF), non-controlled atrial arrhythmias or
clinically significant arrhythmias including conduction abnormality, nodal junctional
arrhythmias and dysrhythmias, sinus bradycardia or tachycardia, supraventricular
arrhythmias, atrial fibrillation or flutter, syncope or vasovagal episodes

15. Electrocardiogram (ECG) with evidence of prior myocardial infarction (e.g.,
significant Q waves), QTc > 450 msec or other clinically significant abnormalities

16. Taking any drug(s) known to prolong the QTc interval, which cannot be interrupted for
at least four days during each treatment cycle.

17. Known significant heart wall abnormality or heart muscle damage as evidenced on
multiple-gated acquisition (MUGA) scan or echocardiogram (this is not a required
screening investigation)

18. Uncontrolled hypertension (defined as blood pressure consistently greater than 150/100
irrespective of medication). Or controlled hypertension requiring use of > 2 classes
of anti-hypertensives.

19. Uncontrolled hypokalemia and/or hypomagnesemia

20. Symptomatic peripheral vascular disease or cerebrovascular disease

21. Psychiatric disorders or other conditions rendering subjects incapable of complying
with the requirements of the protocol

22. Receiving concurrent hormonal therapy with the exception of gonadotropin-releasing
hormone (GnRH) agonists in subjects with hormone refractory prostate cancer, hormone
replacement therapy (HRT), oral contraceptives, and megestrol acetate used for
anorexia/cachexia

23. Receiving anticoagulation with warfarin, heparin or low molecular weight heparin other
than low dose (1 mg) warfarin for maintenance of central line patency

24. Women who are currently pregnant, nursing, or planning a pregnancy; or women who have
a positive pregnancy test.

25. Receiving concurrent antineoplastic therapy (radiation therapy, cytotoxic or biologic
therapy)

26. Participation in an investigational drug or device trial within 30 days of entering
the study.