A Phase I Trial of Combretastatin A4 Phosphate in Patients With Solid Tumours Given by Weekly Intravenous Infusion


Phase 1
18 Years
N/A
Open (Enrolling)
Both
Unspecified Adult Solid Tumor, Protocol Specific

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Trial Information

A Phase I Trial of Combretastatin A4 Phosphate in Patients With Solid Tumours Given by Weekly Intravenous Infusion


OBJECTIVES: I. Determine the toxicity profile, including dose limiting toxicity, and maximum
tolerated dose (MTD) of combretastatin A4 phosphate in patients with advanced solid
malignant tumors. II. Determine the pharmacokinetics of combretastatin A4 phosphate. III.
Assess the effects of combretastatin A4 phosphate on tumor blood flow using PET and MRI
scanning techniques, and establish the dose at which these effects occur. IV. Recommend a
dose of combretastatin A4 phosphate for phase II evaluation based on tumor blood flow effect
and the MTD. V. Evaluate possible antitumor effects of this regimen in these patients.

OUTLINE: This is an open label, dose escalation, multicenter study. Patients receive IV
combretastatin A4 phosphate over 10 minutes once a week for 3 weeks. Patients not
experiencing unacceptable toxic effects begin individual dose escalation, receiving a
maximum of 3 dose levels with 2 weeks of rest between each dose level. Dose escalation stops
when 2 patients have experienced dose limiting toxicity (DLT) at a particular dose level.
Once DLT is established, at least 6 patients are treated at a lower dose to determine the
maximum tolerated dose. Patients may receive up to 6 courses of 3 infusions each. Patients
are followed for 4 weeks.

PROJECTED ACCRUAL: Approximately 30-35 patients will be accrued for this study.

Inclusion Criteria


DISEASE CHARACTERISTICS: Histologically confirmed solid tumor that is not amenable to any
standard curative therapy or is refractory to conventional therapy Tumor suitable for MRI
or PET imaging No active brain metastases

PATIENT CHARACTERISTICS: Age: 18 and over Performance status: WHO 0-2 Life expectancy: At
least 4 months Hematopoietic: WBC at least 4,000/mm3 Platelet count at least 100,000/mm3
Hemoglobin at least 10 g/dL Hepatic: Bilirubin less than 1.17 mg/dL ALT or AST less than 2
times upper limit of normal (ULN) Alkaline phosphatase less than 2 times ULN (unless due
to liver or bone metastases) Renal: Creatinine less than 1.5 mg/dL Cardiovascular: No
ischemic heart disease Other: Not pregnant or nursing Fertile patients must use effective
contraception at least 4 weeks before, during, and for 4 weeks after the study No other
serious medical condition or serious infection within past 28 days No other active
concurrent malignancies, except: Carcinoma in situ of the cervix Adequately treated basal
or squamous cell carcinoma of the skin No autoimmune disorders No inflammatory bowel
disease No diabetes

PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: At least 6 weeks
since prior nitrosoureas or mitomycin and recovered Endocrine therapy: Concurrent steroid
use allowed Radiotherapy: At least 6 weeks since prior radiotherapy (except radiotherapy
to small isolated fields not including significant areas of bone marrow) and recovered No
prior radiotherapy to tumor site(s) that will be imaged by MRI/PET scanning or used to
assess tumor response Surgery: No concurrent open surgery Other: At least 4 weeks since
all other prior anticancer therapies and recovered No concurrent heparin or warfarin
Concurrent NSAIDs allowed

Type of Study:

Interventional

Study Design:

Primary Purpose: Treatment

Principal Investigator

Gordon J.S. Rustin, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Mount Vernon Cancer Centre at Mount Vernon Hospital

Authority:

United States: Federal Government

Study ID:

CDR0000066805

NCT ID:

NCT00003698

Start Date:

July 1998

Completion Date:

Related Keywords:

  • Unspecified Adult Solid Tumor, Protocol Specific
  • unspecified adult solid tumor, protocol specific
  • Neoplasms

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