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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00395434
Recruitment Status : Completed
First Posted : November 2, 2006
Last Update Posted : October 31, 2011
Information provided by (Responsible Party):
Mateon Therapeutics

Brief 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.

Condition or disease Intervention/treatment Phase
Tumors Drug: Combretastatin A4 Phosphate (CA4P) Drug: Bevacizumab (Avastin) Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: OXC4P1-105: A Phase I Study of the Safety, Tolerability, and Antitumor Activity of Escalating Doses of Combretastatin A4 Phosphate Given in Combination With Bevacizumab to Subjects With Advanced Solid Tumors
Study Start Date : September 2006
Actual Primary Completion Date : January 2007
Actual Study Completion Date : January 2007

Resource links provided by the National Library of Medicine

Drug Information available for: Bevacizumab

Primary Outcome Measures :
  1. safety and tolerability of the combination therapy assessed by analysis of adverse events
  2. safety and tolerability of the combination therapy assessed by analysis of laboratory tests
  3. safety and tolerability of the combination therapy assessed by analysis of other assessments within the protocol

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00395434

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United Kingdom
Mount Vernon Hospital
Northwood, Middlesex, United Kingdom, HA6 2RN
Royal Marsden Hospital
Sutton, Surrey, United Kingdom, SM2 5PT
Sponsors and Collaborators
Mateon Therapeutics
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Principal Investigator: Paul Nathan, MD Mount Vernon Hospital
Study Director: Hillori Connors, MS Mateon Therapeutics
Study Director: Peter Harris, MD Mateon Therapeutics

Additional Information:
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Responsible Party: Mateon Therapeutics Identifier: NCT00395434     History of Changes
Other Study ID Numbers: OXC4P1-105
First Posted: November 2, 2006    Key Record Dates
Last Update Posted: October 31, 2011
Last Verified: October 2011
Keywords provided by Mateon Therapeutics:
Advanced Solid Tumors
Advanced Solid Tumours
Advanced Solid Tumor
Advanced Solid Tumour
Malignant Solid Tumors
Malignant Solid Tumours
Malignant Solid Tumor
Malignant Solid Tumour
Metastatic Cancer
Metastatic Disease
Advanced Cancer
Vascular Disrupting Agent
Anti-angiogenesis agent
Phase 1
Additional relevant MeSH terms:
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Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action