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FMISO-PET in Brain Tumors and SCS Effect (FMISOPETSCS)

Primary Purpose

Malignant Glioma

Status
Terminated
Phase
Phase 2
Locations
Spain
Study Type
Interventional
Intervention
18F-FMISO
PET without SCS
SCS
PET without/with SCS
Radiotherapy
Temozolomide
Sponsored by
Bernardino Clavo, MD, PhD
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Malignant Glioma focused on measuring Anaplastic Astrocytoma, Brain Tumors, Cancer Imaging, Fluoromisonidazole, FMISO PET, Glioblastoma, High Grade Glioma, Hypoxia Modification, Positron Emission Tomography, Radiation-Sensitizing Agents, Spinal Cord Stimulation, Tumor Hypoxia Measurement

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients with pathologically confirmed (first presentation or relapsed) high grade glioma (Grade III or Grade IV according WHO criteria) proposed for radical treatment with 3D radiotherapy and temozolomide.
  • Patients 18-75 years old.
  • Karnofsky >= 60% and ECOG =< 2.
  • Signed informed consent.

Exclusion Criteria:

  • Clinical or psychological contraindications to fly (if 18F-FMISO-PET is realized in Madrid) or to SCS-placement (only for this subset).
  • Pregnant or breastfeeding women and women of fertile age who are not using a safe contraceptive method or do not intend to use one during the trial. Safe contraceptive methods are oral or parenteral contraceptive treatments or barrier methods: masculine or feminine condom, diaphragm and/or intrauterine device (IUD) or withdrawal over the course of the study.
  • Serious co-existing or concurrent illness, including any of the following: uncontrolled or severe infection, heart, liver or kidney disease
  • Lung thromboembolism.
  • Another malignancy in the last 5 years other than basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix.
  • Patients with life expectancy <3 months.
  • Patients with any of the following: creatinine > 2 mg/dl, neutrophils <1.5 * 10^9/L, platelets <100 * 10^9/L or hemoglobin <8.5 g/dL.
  • Contraindications to receive radiotherapy or chemotherapy Clinical or psychological contraindications for placement of spinal cord stimulation devices (only for that specific subset of patients).
  • Patients who are unable or unwilling to meet the protocol study.
  • Patients who do not meet all the inclusion criteria.

Sites / Locations

  • Dr. Negrin University Hospital
  • Instituto Tecnologico Servicios Sanitarios, in MD Anderson Cancer Center, Madrid

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Other

Arm Label

Arm-A: 18F-FMISO-PET without SCS

Arm-B: 18F-FMISO-PET without/with SCS

Arm Description

One 18F-FMISO-PET study for assessment of tumor hypoxia before radiotherapy and Temozolomide, without spinal cord stimulation.

Two 18F-FMISO-PET studies for assessment of tumor hypoxia before radiotherapy and Temozolomide: one "without" and one "with" spinal cord stimulation

Outcomes

Primary Outcome Measures

Tumor hypoxia measurement using 18F-FMISO-PET (hypoxic volume and tumor/muscle ratio). Baseline measurement.
Tumor hypoxia will be measured in 20 patients with HGG using 18F-FMISO-PET: after biopsy or surgery and before the commencement of radio-chemotherapy. It will be assessed the prevalence and extent of significant hypoxia in HGG.
Change from baseline tumor hypoxia using 18F-FMISO-PET (hypoxic volume and tumor/muscle ratio) during SCS.
A subset of 10 patients will undergo a second 18F-FMISO-PET study during spinal cord stimulation to evaluate changes by SCS between 1 and 7 days after the first 18F-FMISO-PET study (and before the commencement of radio-chemotherapy).

Secondary Outcome Measures

Correlation between 18F-FMISO-PET values and pathological tumor parameters
To analyze the correlation of 18F-FMISO-PET with histological parameters and tumor expression of: CD31 (vascular density), VEGF (vascular endothelial growth factor) and VEGFR (angiogenesis), EGFR (epidermal growth factor receptor), Ki-67 (proliferation index) and hypoxic markers
Correlation with Karnofsky scale.
To analyze the correlation with performance status using the Karnofsky scale.
Correlation with the ECOG (Eastern Cooperative Oncology Group) performance status scale
To analyze the correlation with performance status using the ECOG (WHO) scale.
Correlation with the Quality of Life Questionnaire QLQ-C30 (EORTC)
To analyze the correlation with quality of life using the QLQ-C30 (EORTC) questionnaire.
Overall survival.
To analyze the correlation with overall survival.
Radiological response to treatment
To analyze the correlation between 18F-FMISO-PET values and radiological response to treatment
Radiological location of tumor relapse or progression
To analyze the correlation between 18F-FMISO-PET values and the radiological location of tumor relapse or progression

Full Information

First Posted
May 24, 2010
Last Updated
August 23, 2018
Sponsor
Bernardino Clavo, MD, PhD
Collaborators
Instituto Tecnologico Servicios Sanitarios, in MD Anderson Cancer Center, Madrid, Instituto de Salud Carlos III, Grupo de Investigación Clínica en Oncología Radioterapia, Instituto Canario de Investigación del Cáncer, RSbiomed, Fundación DISA, Canary Islands, Spain
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1. Study Identification

Unique Protocol Identification Number
NCT01868906
Brief Title
FMISO-PET in Brain Tumors and SCS Effect
Acronym
FMISOPETSCS
Official Title
Positron Emission Tomography With Fluoro-misonidazole (PET-FMISO) in High Grade Gliomas: Assessment of Tumor Hypoxia and Effect of Spinal Cord Stimulation
Study Type
Interventional

2. Study Status

Record Verification Date
August 2018
Overall Recruitment Status
Terminated
Why Stopped
Isotope (FMISO) production is no longer available in our country.
Study Start Date
June 2013 (undefined)
Primary Completion Date
September 17, 2017 (Actual)
Study Completion Date
September 17, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Bernardino Clavo, MD, PhD
Collaborators
Instituto Tecnologico Servicios Sanitarios, in MD Anderson Cancer Center, Madrid, Instituto de Salud Carlos III, Grupo de Investigación Clínica en Oncología Radioterapia, Instituto Canario de Investigación del Cáncer, RSbiomed, Fundación DISA, Canary Islands, Spain

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The aim of this study is to assess, with 18F-FMISO PET, hypoxia in high grade gliomas and changes by spinal cord stimulation in a subset of patients. Additionally, the potential correlation with pathological, imaging and clinical parameters will be analyzed.
Detailed Description
Tumour ischaemia-hypoxia decreases the efficacy of radio-chemotherapy. Polarographic probe (and some 18F-FMISO-PET) studies have demonstrated prognostic value. Additionally hypoxia modification may increase survival. However, in high grade gliomas (HGG) there are not well established methods to evaluate and modify tumor hypoxia. We have previously described how spinal cord stimulation (SCS) can modify oxygenation, blood flow and metabolism in malignant gliomas. The aim of this study is to assess with 18F-FMISO PET: hypoxia in HGG and changes by spinal cord stimulation in a subset of patients. Additionally, the potential correlation with pathological, imaging and clinical parameters will be analyzed. 18F-FMISO PET will be performed in 20 patients with diagnosis of HGG: after surgery/biopsy and before radical treatment with 3D radiotherapy and temozolomide. A subset of 10 patients undergo two studies with 18F- FMISO-PET (one with SCS "off" and one with SCS "on"). In these patients, SCS will be connected from 1 hour before to 1 hour after each radiotherapy session, and in the day-time during the days of adjuvant temozolomide. 18F-FMISO PET results will not be taking into account for patient management. Patients will be followed at least until the end of adjuvant temozolomide (6 months after the end of concurrent radiochemotherapy).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Malignant Glioma
Keywords
Anaplastic Astrocytoma, Brain Tumors, Cancer Imaging, Fluoromisonidazole, FMISO PET, Glioblastoma, High Grade Glioma, Hypoxia Modification, Positron Emission Tomography, Radiation-Sensitizing Agents, Spinal Cord Stimulation, Tumor Hypoxia Measurement

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
6 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm-A: 18F-FMISO-PET without SCS
Arm Type
Other
Arm Description
One 18F-FMISO-PET study for assessment of tumor hypoxia before radiotherapy and Temozolomide, without spinal cord stimulation.
Arm Title
Arm-B: 18F-FMISO-PET without/with SCS
Arm Type
Other
Arm Description
Two 18F-FMISO-PET studies for assessment of tumor hypoxia before radiotherapy and Temozolomide: one "without" and one "with" spinal cord stimulation
Intervention Type
Drug
Intervention Name(s)
18F-FMISO
Other Intervention Name(s)
Fluoromisonidazole, FMISO
Intervention Description
18F-FMISO-PET scanning, for tumor hypoxia assessment before radio-chemotherapy.
Intervention Type
Procedure
Intervention Name(s)
PET without SCS
Other Intervention Name(s)
Positron emission tomography scanning
Intervention Description
PET-scanning using 18F-fluoromisonidazole without SCS
Intervention Type
Device
Intervention Name(s)
SCS
Other Intervention Name(s)
Electrical Neurostimulation, Spinal Cord Stimulation
Intervention Description
Electrical stimulation of spinal cord, minimally invasive neurosurgical technique used to treat refractory pain and ischemic syndromes.
Intervention Type
Procedure
Intervention Name(s)
PET without/with SCS
Other Intervention Name(s)
Positron emission tomography scanning
Intervention Description
Second PET-scanning using 18F-fluoromisonidazole: without/with SCS
Intervention Type
Radiation
Intervention Name(s)
Radiotherapy
Other Intervention Name(s)
Radiation therapy
Intervention Description
Standard radiation therapy
Intervention Type
Drug
Intervention Name(s)
Temozolomide
Other Intervention Name(s)
Temodar, Temodal, Temcad
Intervention Description
Standard treatment with concurrent and adjuvant Temozolomide.
Primary Outcome Measure Information:
Title
Tumor hypoxia measurement using 18F-FMISO-PET (hypoxic volume and tumor/muscle ratio). Baseline measurement.
Description
Tumor hypoxia will be measured in 20 patients with HGG using 18F-FMISO-PET: after biopsy or surgery and before the commencement of radio-chemotherapy. It will be assessed the prevalence and extent of significant hypoxia in HGG.
Time Frame
18F-FMISO-PET between 1 and 3 weeks before the commencement of radio-chemotherapy
Title
Change from baseline tumor hypoxia using 18F-FMISO-PET (hypoxic volume and tumor/muscle ratio) during SCS.
Description
A subset of 10 patients will undergo a second 18F-FMISO-PET study during spinal cord stimulation to evaluate changes by SCS between 1 and 7 days after the first 18F-FMISO-PET study (and before the commencement of radio-chemotherapy).
Time Frame
2nd 18F-FMISO-PET between 1 and 7 days after the 1st 18F-FMISO-PET
Secondary Outcome Measure Information:
Title
Correlation between 18F-FMISO-PET values and pathological tumor parameters
Description
To analyze the correlation of 18F-FMISO-PET with histological parameters and tumor expression of: CD31 (vascular density), VEGF (vascular endothelial growth factor) and VEGFR (angiogenesis), EGFR (epidermal growth factor receptor), Ki-67 (proliferation index) and hypoxic markers
Time Frame
Week 0 (at the commencement of radio-chemotherapy).
Title
Correlation with Karnofsky scale.
Description
To analyze the correlation with performance status using the Karnofsky scale.
Time Frame
At 0, 2 and 9 months after the commencement of the radio-chemotherapy.
Title
Correlation with the ECOG (Eastern Cooperative Oncology Group) performance status scale
Description
To analyze the correlation with performance status using the ECOG (WHO) scale.
Time Frame
At 0, 2 and 9 months after the commencement of the radio-chemotherapy
Title
Correlation with the Quality of Life Questionnaire QLQ-C30 (EORTC)
Description
To analyze the correlation with quality of life using the QLQ-C30 (EORTC) questionnaire.
Time Frame
At 0, 2 and 9 months after the commencement of the radio-chemotherapy.
Title
Overall survival.
Description
To analyze the correlation with overall survival.
Time Frame
At 9 months after the commencement of the radio-chemotherapy.
Title
Radiological response to treatment
Description
To analyze the correlation between 18F-FMISO-PET values and radiological response to treatment
Time Frame
9 months after the commencement of radio-chemotherapy
Title
Radiological location of tumor relapse or progression
Description
To analyze the correlation between 18F-FMISO-PET values and the radiological location of tumor relapse or progression
Time Frame
9 months after the commencement of radio-chemotherapy
Other Pre-specified Outcome Measures:
Title
Blood flow in carotid and middle cerebral arteries
Description
To analyze the correlation between 18F-FMISO-PET values and blood flow in carotid and middle cerebral arteries (assessed before the commencement of radio-chemotherapy) using Doppler measurements.
Time Frame
Between 1 and 3 weeks before the commencement of radio-chemotherapy
Title
Facial and supraciliar infrared emission
Description
To analyze the correlation between 18F-FMISO-PET values and facial and supraciliar infrared emission (assessed by digital thermography)
Time Frame
Between 1 and 3 weeks before the commencement of radio-chemotherapy

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients with pathologically confirmed (first presentation or relapsed) high grade glioma (Grade III or Grade IV according WHO criteria) proposed for radical treatment with 3D radiotherapy and temozolomide. Patients 18-75 years old. Karnofsky >= 60% and ECOG =< 2. Signed informed consent. Exclusion Criteria: Clinical or psychological contraindications to fly (if 18F-FMISO-PET is realized in Madrid) or to SCS-placement (only for this subset). Pregnant or breastfeeding women and women of fertile age who are not using a safe contraceptive method or do not intend to use one during the trial. Safe contraceptive methods are oral or parenteral contraceptive treatments or barrier methods: masculine or feminine condom, diaphragm and/or intrauterine device (IUD) or withdrawal over the course of the study. Serious co-existing or concurrent illness, including any of the following: uncontrolled or severe infection, heart, liver or kidney disease Lung thromboembolism. Another malignancy in the last 5 years other than basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix. Patients with life expectancy <3 months. Patients with any of the following: creatinine > 2 mg/dl, neutrophils <1.5 * 10^9/L, platelets <100 * 10^9/L or hemoglobin <8.5 g/dL. Contraindications to receive radiotherapy or chemotherapy Clinical or psychological contraindications for placement of spinal cord stimulation devices (only for that specific subset of patients). Patients who are unable or unwilling to meet the protocol study. Patients who do not meet all the inclusion criteria.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bernardino Clavo, MD, PhD
Organizational Affiliation
Dr. Negrin University Hospital, Las Palmas
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Bernardino Clavo, MD, PhD
Organizational Affiliation
Dr. Negrin University Hospital, Las Palmas
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Francisco Robaina, MD, PhD
Organizational Affiliation
Dr. Negrin University Hospital, Las Palmas
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Juan C Alonso, MD, PhD
Organizational Affiliation
Instituto Tecnologico Servicios Sanitarios, in MD Anderson Cancer Center, Madrid
Official's Role
Principal Investigator
Facility Information:
Facility Name
Dr. Negrin University Hospital
City
Las Palmas
ZIP/Postal Code
35010
Country
Spain
Facility Name
Instituto Tecnologico Servicios Sanitarios, in MD Anderson Cancer Center, Madrid
City
Madrid
ZIP/Postal Code
28.033
Country
Spain

12. IPD Sharing Statement

Citations:
PubMed Identifier
11795721
Citation
Clavo B, Robaina F, Morera J, Ruiz-Egea E, Perez JL, Macias D, Carames MA, Catala L, Hernandez MA, Gunderoth M. Increase of brain tumor oxygenation during cervical spinal cord stimulation. Report of three cases. J Neurosurg. 2002 Jan;96(1 Suppl):94-100. doi: 10.3171/spi.2002.96.1.0094.
Results Reference
background
PubMed Identifier
12816274
Citation
Clavo B, Robaina F, Catala L, Valcarcel B, Morera J, Carames MA, Ruiz-Egea E, Panero F, Lloret M, Hernandez MA. Increased locoregional blood flow in brain tumors after cervical spinal cord stimulation. J Neurosurg. 2003 Jun;98(6):1263-70. doi: 10.3171/jns.2003.98.6.1263.
Results Reference
background
PubMed Identifier
15111351
Citation
Clavo B, Robaina F, Catala L, Perez JL, Lloret M, Carames MA, Morera J, Lopez L, Suarez G, Macias D, Rivero J, Hernandez MA. Effect of cervical spinal cord stimulation on regional blood flow and oxygenation in advanced head and neck tumours. Ann Oncol. 2004 May;15(5):802-7. doi: 10.1093/annonc/mdh189.
Results Reference
background
PubMed Identifier
16619657
Citation
Clavo B, Robaina F, Montz R, Domper M, Carames MA, Morera J, Pinar B, Hernandez MA, Santullano V, Carreras JL. Modification of glucose metabolism in brain tumors by using cervical spinal cord stimulation. J Neurosurg. 2006 Apr;104(4):537-41. doi: 10.3171/jns.2006.104.4.537.
Results Reference
background
PubMed Identifier
22151123
Citation
Robaina F, Clavo B, Catala L, Carames MA, Morera J. Blood flow increase by cervical spinal cord stimulation in middle cerebral and common carotid arteries. Neuromodulation. 2004 Jan;7(1):26-31. doi: 10.1111/j.1525-1403.2004.04003.x.
Results Reference
background
PubMed Identifier
18513465
Citation
Clavo B, Robaina F, Montz R, Carames MA, Otermin E, Carreras JL. Effect of cervical spinal cord stimulation on cerebral glucose metabolism. Neurol Res. 2008 Jul;30(6):652-4. doi: 10.1179/174313208X305373. Epub 2008 May 29.
Results Reference
background
PubMed Identifier
19499176
Citation
Clavo B, Robaina F, Montz R, Carames MA, Lloret M, Ponce P, Hernandez MA, Carreras JL. Modification of glucose metabolism in radiation-induced brain injury areas using cervical spinal cord stimulation. Acta Neurochir (Wien). 2009 Nov;151(11):1419-25. doi: 10.1007/s00701-009-0400-8. Epub 2009 Jun 5.
Results Reference
background
PubMed Identifier
21748490
Citation
Clavo B, Robaina F, Valcarcel B, Catala L, Perez JL, Cabezon A, Jorge IJ, Fiuza D, Hernandez MA, Jover R, Carreras JL. Modification of loco-regional microenvironment in brain tumors by spinal cord stimulation. Implications for radio-chemotherapy. J Neurooncol. 2012 Jan;106(1):177-84. doi: 10.1007/s11060-011-0660-z. Epub 2011 Jul 12.
Results Reference
background
PubMed Identifier
17827455
Citation
Overgaard J. Hypoxic radiosensitization: adored and ignored. J Clin Oncol. 2007 Sep 10;25(26):4066-74. doi: 10.1200/JCO.2007.12.7878.
Results Reference
background
PubMed Identifier
18451225
Citation
Spence AM, Muzi M, Swanson KR, O'Sullivan F, Rockhill JK, Rajendran JG, Adamsen TC, Link JM, Swanson PE, Yagle KJ, Rostomily RC, Silbergeld DL, Krohn KA. Regional hypoxia in glioblastoma multiforme quantified with [18F]fluoromisonidazole positron emission tomography before radiotherapy: correlation with time to progression and survival. Clin Cancer Res. 2008 May 1;14(9):2623-30. doi: 10.1158/1078-0432.CCR-07-4995.
Results Reference
background
PubMed Identifier
25228535
Citation
Clavo B, Robaina F, Jorge IJ, Cabrera R, Ruiz-Egea E, Szolna A, Otermin E, Llontop P, Carames MA, Santana-Rodriguez N, Sminia P. Spinal cord stimulation as adjuvant during chemotherapy and reirradiation treatment of recurrent high-grade gliomas. Integr Cancer Ther. 2014 Nov;13(6):513-9. doi: 10.1177/1534735414550037. Epub 2014 Sep 15.
Results Reference
background
PubMed Identifier
27527617
Citation
Clavo B, Robaina F, Fiuza D, Ruiz A, Lloret M, Rey-Baltar D, Llontop P, Riveros A, Rivero J, Castaneda F, Quintero S, Santana-Rodriguez N. Predictive value of hypoxia in advanced head and neck cancer after treatment with hyperfractionated radio-chemotherapy and hypoxia modification. Clin Transl Oncol. 2017 Apr;19(4):419-424. doi: 10.1007/s12094-016-1541-x. Epub 2016 Aug 15.
Results Reference
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FMISO-PET in Brain Tumors and SCS Effect

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