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

NCT00395434 | Completed Phase 1

• 1 other identifier: OXC4P1-105
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 2

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.

Conditions

Tumors

Keywords

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

Outcome Measures

Primary Outcomes (3)

• 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

Interventions

Combretastatin A4 Phosphate (CA4P) DRUG

Bevacizumab (Avastin) DRUG

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histopathologically or cytologically confirmed malignant solid tumors that have failed standard therapy or for which no life prolonging treatment exists
• Measurable disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria
• 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)
• Age \> or = to 18 years old
• Adequate bone marrow function:
• absolute granulocyte count (neutrophils and bands) \> or = to 1500 cells/mm3;
• platelet count \> or = to 100,000 cells/mm3;
• hemoglobin \> or = to 9 g/dL.
• Adequate renal function (glomerular filtration calculated by Cockcroft/Gault formula or measure urine creatinine clearance \> or = to 50 mL/minute)
• Adequate hepatic function:
• bilirubin less than or = to 1.5 mg/dL;
• 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).
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Life expectancy of \> or = to 12 weeks
• 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

You may not qualify if:

• 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)
• Presence of central nervous system (CNS) metastases
• Diagnosed squamous non-small cell lung cancer (NSCLC)
• History of gastrointestinal perforations
• Surgery within 28 days of screening visit or a surgical incision that is not fully healed. Any surgery planned during the study period.
• Proteinuria \>1 g/24 hours by 24 hour urine collection (perform 24 hour urine collection if \> 1+ on dipstick)
• Recent hemoptysis (occurrence within the past 3 months)
• Prior therapy with CA4P or bevacizumab, or other agents which target vascular endothelial growth factor (VEGF) or VEGFR signaling such as Sorafenib and Sutent
• Prior radiation involving \> 30% of the bone marrow
• 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.
• Active autoimmune disorder(s)
• Immunocompromised, including subjects known to be human immunodeficiency virus (HIV) positive
• Active infection requiring antibiotic therapy or any other serious intercurrent illness
• 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
• Electrocardiogram (ECG) with evidence of prior myocardial infarction (e.g., significant Q waves), QTc \> 450 msec or other clinically significant abnormalities

Sponsors & Collaborators

• Mateon Therapeutics: lead

Study Sites (2)

Mount Vernon Hospital

Northwood, Middlesex, HA6 2RN, United Kingdom

Location

Royal Marsden Hospital

Sutton, Surrey, SM2 5PT, United Kingdom

Location

MeSH Terms

Conditions

Neoplasms; Neoplasm Metastasis

Interventions

fosbretabulin; Bevacizumab

Condition Hierarchy (Ancestors)

Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Paul Nathan, MD

  Mount Vernon Hospital

  PRINCIPAL INVESTIGATOR

• Hillori Connors, MS

  Mateon Therapeutics

  STUDY DIRECTOR

• Peter Harris, MD

  Mateon Therapeutics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 1, 2006
• First Posted: November 2, 2006
• Study Start: September 1, 2006
• Primary Completion: January 1, 2007
• Study Completion: January 1, 2007
• Last Updated: October 31, 2011

Record last verified: 2011-10

Locations

GB (2)