Clinical trial NCT00602199: ABT-510 in Treating Patients With Metastatic Melanoma
Official title: A Phase II Study of Anti-angiogenesis Therapy for Metastatic Melanoma Using ABT-510
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Melanoma (Skin)
Keywords: stage IV melanoma
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2008-01-28
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: RATIONALE: ABT-510 may stop the growth of melanoma by blocking blood flow to the tumor.

PURPOSE: This phase II trial is studying how well giving ABT-510 works in treating patients with metastatic melanoma.

Detailed description: OBJECTIVES:

* Examine the safety profile of ABT-510 in patients with metastatic malignant melanoma.
* Examine the antitumor activity (i.e., time to progression and response rates) in patients treated with ABT-510.
* Determine the pharmacodynamic effects of ABT-510 and its potential impact on immune cell function in these patients.

OUTLINE: Patients receive ABT-510 subcutaneously twice daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Blood samples are obtained at baseline, before treatment on day 1 of cycles 2 and 3, and then every other course thereafter for pharmacological and ancillary studies. Samples are evaluated for EC enumeration, expression profiling, circulating tumor cell quantification, analysis of T-cell functions (i.e., immunophenotyping for NK-, T- and B-cell phenotypes as well as ELISPOT analysis against common environmental pathogens and T cell spectratyping), and angiogenesis bioassays. Patients also undergo ultrasound-guided core tumor biopsies for histological analysis of microvascular density (CD38 and von Willebrand Factor immunohistochemistry) at baseline and before treatment on day 1 of courses 3 and 5.

After completion of study treatment, patients are followed every 3 months for up to 5 years.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed malignant melanoma

  * Stage IV disease
  * No known potentially curative standard therapy that exists or is proven capable of extending life expectancy
* Measurable disease
* No history of or current CNS metastases

  * MRI of the brain to confirm absence of CNS metastases within the past 28 days is required
* No known, presently active carcinomatous meningitis

PATIENT CHARACTERISTICS:

* ECOG performance status 0-2
* Life expectancy ≥ 6 months
* ANC ≥ 1,500/mm³
* Platelet count ≥ 100,000/mm³
* Alkaline phosphatase ≤ 3 times upper limit of normal (ULN)
* AST ≤ 3 times ULN
* Creatinine ≤ 2.5 times ULN
* Hemoglobin ≥ 9.0 g/dL
* Prothrombin time normal
* Willing to return to Mayo Clinic Rochester, Jacksonville or Scottsdale for follow-up
* Must be able to self-administer or has a caregiver who can reliably administer subcutaneous injections
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No uncontrolled or current infection
* No New York Heart Association class III-IV heart disease
* No recent history of (i.e., ≤ 12 weeks from study day 1) or current cancer-related bleeding event (e.g., hemoptysis)
* No recent history of (within the past 4 weeks) or current noncancer-related clinically significant bleeding event
* No uncontrolled hypertension
* No history of stroke or other CNS bleeding events (e.g., aneurysms)

PRIOR CONCURRENT THERAPY:

* At least 4 weeks since prior chemotherapy and recovered (6 weeks for mitomycin C or nitrosoureas)
* At least 4 weeks since prior immunotherapy, biologic therapy, radiotherapy, or surgery
* No concurrent anticoagulation therapy or antiplatelet therapy
* No other concurrent antineoplastic agents (e.g., cytotoxic chemotherapy, immunotherapy, radiotherapy, or investigational therapy) except local radiotherapy for supportive reasons involving a small radiation field

Primary outcomes:
measure: 18-week progression-free survival rate
Secondary outcomes:
measure: Objective response rate as defined by RECIST criteria
measure: Overall survival time
measure: Frequency of NK-cells, T-cells, and B-cells before the start of the first 5 courses of treatment
Other outcomes:
Locations:
Study officials:
affiliation: Mayo Clinic
name: Svetomir Markovic, MD, PhD
role: STUDY_CHAIR
References:
citation: Markovic SN, Suman VJ, Rao RA, Ingle JN, Kaur JS, Erickson LA, Pitot HC, Croghan GA, McWilliams RR, Merchan J, Kottschade LA, Nevala WK, Uhl CB, Allred J, Creagan ET. A phase II study of ABT-510 (thrombospondin-1 analog) for the treatment of metastatic melanoma. Am J Clin Oncol. 2007 Jun;30(3):303-9. doi: 10.1097/01.coc.0000256104.80089.35.