Boron Neutron Capture Therapy Using Boronophenylalanine-Fructose Complex in Treating Patients With Metastatic Melanoma

Early Phase II Study On BNCT In Metastatic Malignant Melanoma Using The Boron Carrier BPA

RATIONALE: Boron neutron capture therapy using boronophenylalanine-fructose complex may kill tumor cells without harming normal tissue.

PURPOSE: This phase II trial is studying how well boron neutron capture therapy using boronophenylalanine-fructose complex works in treating patients with metastatic melanoma.

Study Overview

• Status: Terminated
• Conditions: Melanoma (Skin)
• Intervention / Treatment: Drug: boronophenylalanine-fructose complex

Detailed Description

OBJECTIVES:

Primary

• Determine the therapeutic activity and efficacy of boron neutron capture therapy using boronophenylalanine-fructose complex in patients with metastatic melanoma.
• Determine the objective local response in patients treated with this regimen.

Secondary

• Determine the overall survival of patients treated with this regimen.
• Determine the duration of local response and time to local progression in patients treated with this regimen.
• Determine the dose-response relationship at the per-lesion level in patients treated with this regimen.
• Determine the safety of this regimen in these patients.
• Determine the toxicity of this regimen in these patients.

OUTLINE: This is an open-label study.

Patients receive boronophenylalanine-fructose complex IV over 90 minutes followed by boron neutron capture therapy on days 1 and 2.

Patients are followed at 1 and 6 weeks and then every 8 weeks thereafter. In the event of disease progression, patients are followed every 3 months for survival.

PROJECTED ACCRUAL: A total of 16-24 patients will be accrued for this study.

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Essen, Germany, D-45122
    • Universitaetsklinikum Essen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Histologically confirmed melanoma

  • Metastatic disease

    • Brain metastases, skin metastases, or soft tissue metastases of the head and neck or the extremities
  • Accessible lesion(s) for boron neutron capture therapy (BNCT)
  • No clear progression of disease at other sites than the ones intended for treatment with surgery and/or BNCT

• Measurable disease by MRI within the past 4 weeks

  • Lesion(s) ≥ 10 mm in diameter
• Indication for palliative radiotherapy that is intended to be delivered as BNCT

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Karnofsky 70-100%

Life expectancy

• Not specified

Hematopoietic

• Neutrophil count ≥ 2,000/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 10 g/dL

Hepatic

• Bilirubin ≤ 2.5 times upper limit of normal (ULN)*
• Transaminases ≤ 2.5 times ULN*
• Alkaline phosphatase ≤ 2.5 times ULN* NOTE: *Unless due to reversible reaction to antiseizure medication

Renal

• Creatinine ≤ 2.5 times ULN
• Blood urea nitrogen ≤ 2.5 times ULN

Cardiovascular

• No congestive heart failure
• No newly diagnosed or unstable angina pectoris
• No uncontrolled arrhythmias
• No uncontrolled conduction defects
• No recent coronary artery disease
• No other severe heart disease

Pulmonary

• No severe pulmonary disease, including severe obstructive or restrictive lung disease

Other

• No history of phenylketonuria
• No severe gastrointestinal disease
• No active peptic ulcer disease
• No uncontrolled endocrine disease
• No pre-existing serious mental or organic brain disease (e.g., epilepsy)
• No psychological, familial, sociological, or geographical condition that would preclude study compliance
• Able to travel to the Netherlands via public transportation
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No concurrent immunologic or biologic therapy
• No concurrent colony-stimulating factors (e.g., epoetin alfa or filgrastim [G-CSF])

Chemotherapy

• No concurrent chemotherapy

Endocrine therapy

• No concurrent hormonal therapy

Radiotherapy

• No prior radiotherapy to site(s) proposed for study treatment
• No other concurrent radiotherapy

Surgery

• See Disease Characteristics

Other

• Recovered from all prior anti-tumor therapy (excluding alopecia and sensitive peripheral neuropathy ≤ grade 2)
• No other concurrent anticancer therapy
• No other concurrent investigational drugs

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Best response to treatment as measured by RECIST every 8 weeks at completion of study treatment

Secondary Outcome Measures

Outcome Measure
Overall survival as measured every 8 weeks at completion of study treatment
Duration of local response as measured by Kaplan Meier every 8 weeks after completion of study treatment
Time to local progression measured every 8 weeks after completion of study treatment
Acute toxicity as measured by Common Toxicity Criteria AE v 3.0 1- 6 weeks after completion of treatment
Late toxicity as measured by RTOG and EORTC week 6 and thereafter upon completion of study treatment

Collaborators and Investigators

• Sponsor: European Organisation for Research and Treatment of Cancer - EORTC
• Investigators: Study Chair: Andrea Wittig, Universitaetsklinikum Essen

Publications and helpful links

General Publications

• Wittig A, Moss RL, Stecher-Rasmussen F, Appelman K, Rassow J, Roca A, Sauerwein W. Neutron activation of patients following boron neutron capture therapy of brain tumors at the high flux reactor (HFR) Petten (EORTC Trials 11961 and 11011). Strahlenther Onkol. 2005 Dec;181(12):774-82. doi: 10.1007/s00066-005-1433-4.

Study record dates

Study Major Dates

• Study Start: April 1, 2004
• Primary Completion (Actual): October 1, 2006

Study Registration Dates

• First Submitted: June 10, 2004
• First Submitted That Met QC Criteria: June 10, 2004
• First Posted (Estimate): June 11, 2004

Study Record Updates

• Last Update Posted (Estimate): July 18, 2012
• Last Update Submitted That Met QC Criteria: July 17, 2012
• Last Verified: July 1, 2012

More Information

Terms related to this study

• Keywords: recurrent melanoma; stage IV melanoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma
• Other Study ID Numbers: EORTC-11011