18F ML-10 for Early Detection of Response of Brain Metastases to SRS

NCT00696943 | Terminated Phase 2 DMC

• 1 other identifier: NST-CA005CTIL
• Study Type: interventional
• Target: 1
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study is to evaluate the potential of \[18F\]-ML-10 to serve as a non-invasive imaging tool for the early detection of apoptosis in brain metastases in response to radiation therapy, in patients subjected to stereotactic radiosurgery (SRS). Such early detection may improve clinical management of patients with brain metastases, as it may help early identification of non-responders, and subsequently potentially lead to optimization of radiation techniques such as the need for whole brain radiation therapy (WBRT), addition of brain penetrating chemotherapy or an early decision on referral of the patient with non-responsive lesions to surgery or to systemic chemotherapy. The experimental design of the present study aims to evaluate the potential of non-invasive PET examination with \[18F\]-ML-10, to provide the clinician with an assessment of response early in the course of treatment, via non-invasive molecular imaging of radiation-induced apoptosis. This information on tumor responsiveness is currently available only several weeks to months after completion of radiotherapy.

Conditions

Metastasis to Brain of Unknown Primary

Keywords

cell death; PET imaging; brain metastases; stereotactic radiosurgery

Outcome Measures

Primary Outcomes (1)

• Assessment of the change in the uptake of [18F]-ML-10 by the target lesion(s) in response to SRS, as observed by comparing the PET/CT scans before and after SRS. Target lesion is defined as having a minimal diameter of 1.5 cm

  3 months

Secondary Outcomes (2)

• Assessment of the relationship between the change in uptake of [18F]-ML-10 by the metastatic target lesions as observed in the PET/CT scans obtained before and after irradiation, and shrinkage of the metastatic target lesion, as assessed by MRI.

  3 months

• Evaluation of the safety of [18F]-ML-10 when administered for 3 consecutive PET/CT scans to patients with brain metastases undergoing SRS.

  one month

Study Arms (1)

18F-ML-10,

EXPERIMENTAL

Pre-treatment baseline and post treatment follow-up 18F ML-10 PET/CT sessions.

Drug: ([18F]-ML-10)

Interventions

([18F]-ML-10) DRUG

\[18F\]-ML-10 was administered as an intravenous bolus injection (in 3-10 ml sterile saline solution, containing no more than 10% ethanol by volume). The radiation dose of \[18F\]-ML-10 administered at each session was 300-500 MBq (8.1-13.5 mCi).

Also known as: 2-(5-fluoro-pentyl)-2-methyl-malonic-acid

18F-ML-10,

Eligibility Criteria

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

You may qualify if:

• The Patient may only be included in the study if ALL of the following statements are fulfilled:
• Male or female patient diagnosed with metastatic non hematological cancer, with up to 4 brain metastases of which at least one has a minimal diameter of 1.5cm , as assessed by MRI (utilized for SRS planning) and is scheduled for SRS. These metastases will be defined as target lesions.
• Patient is ≥ 18 years of age at the time of signature of the informed consent form.
• Fully conscious patient who has been given written and verbal information, and has then provided an informed consent.
• Patient who is able to cooperate with the studies requirements to lie still during PET/CT imaging scans, which may last for up to 3 hours.
• ECOG performance status of 0, 1 or 2 at the time of enrollment.
• Patient with life expectancy ≥ 12 weeks.
• Adequate renal function and adequate hepatic function as assessed by standard laboratory criteria and defined as:
• Creatinine clearance ≥ 60 ml/min/1.73m2according to Cockroft \& Gault Formula
• Total bilirubin ≤ 1.5 times the ULN
• Aspargine aminotransferase (AST), alanine aminotransferase (ALT) ≤ 3 times the ULN in patients without liver metastases; ≤ 5 times the ULN in patients with liver metastases
• Serum calcium levels, adjusted to albumin level, within normal limits.
• For a female patient, pregnancy or breast-feeding are restricted. Woman of child bearing potential must have a negative serum pregnancy test at screening.

You may not qualify if:

• If any apply, the patient must not be included in the study:
• Unstable medical condition, such as severe ischemic heart disease, liver disease or pulmonary disease, which may risk the patient during the study, as judged by the investigator.
• Any indication of imminent brain herniation
• Any known psychiatric disorder other than mild depression or anxiety.
• Known allergy to Gadolinium
• Other condition that might jeopardize the safety of the patient or the evaluation of the study results, as judged by the investigator.
• Treatment with any non-marketed investigational drug within 30 days prior to administration of \[18F\]-ML-10
• Patient who received Whole Brain Radiation Therapy (WBRT) within 6 months prior screening and/or planned to receive WBRT 8 weeks post SRS
• Patient receiving concurrent treatment with temozolamide or planned to receive temozolamide within 8 weeks post SRS
• Woman of child-bearing potential who is not using an adequate and medically acceptable contraceptive method. Men who do not agree to use effective contraception during the study and for a period of 60 days following the last administration of \[18F\]-ML-10.

Sponsors & Collaborators

• Aposense Ltd.: lead

MeSH Terms

Conditions

Brain Neoplasms

Interventions

5-fluoropentyl-2-methylmalonic acid

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Yael Cohen

  Aposense Ltd.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 11, 2008
• First Posted: June 13, 2008
• Study Start: July 1, 2008
• Primary Completion: July 1, 2009
• Study Completion: July 1, 2009
• Last Updated: February 15, 2013

Record last verified: 2008-11