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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
OXiGENE
ClinicalTrials.gov Identifier:
NCT00395434
First received: November 1, 2006
Last updated: October 28, 2011
Last verified: October 2011
  Purpose

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 Intervention Phase
Tumors
Drug: Combretastatin A4 Phosphate (CA4P)
Drug: Bevacizumab (Avastin)
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by OXiGENE:

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

Estimated Enrollment: 20
Study Start Date: September 2006
Study Completion Date: January 2007
Primary Completion Date: January 2007 (Final data collection date for primary outcome measure)
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00395434

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

Additional Information:
No publications provided

Responsible Party: OXiGENE
ClinicalTrials.gov Identifier: NCT00395434     History of Changes
Other Study ID Numbers: OXC4P1-105
Study First Received: November 1, 2006
Last Updated: October 28, 2011
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by OXiGENE:
Advanced Solid Tumors
Advanced Solid Tumours
Advanced Solid Tumor
Advanced Solid Tumour
Advanced
Malignant
Solid
Tumors
Tumours
Tumor
Tumour
Cancer
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:
Combretastatin
Combretastatin A-4
Bevacizumab
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors

ClinicalTrials.gov processed this record on July 20, 2014