Clinical trial NCT01868906: FMISO-PET in Brain Tumors and SCS Effect
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
Overall status: TERMINATED
Phase: PHASE2
Conditions: 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
Lead sponsor: Dr. Negrin University Hospital
Sponsor class: OTHER
Collaborators: name: Instituto Tecnologico Servicios Sanitarios, in MD Anderson Cancer Center, Madrid
name: Instituto de Salud Carlos III
name: Grupo de Investigación Clínica en Oncología Radioterapia
name: Instituto Canario de Investigación del Cáncer
name: RSbiomed
name: Fundación DISA, Canary Islands, Spain
First posted: 2013-06-05
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

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).

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.

Primary outcomes:
measure: Tumor hypoxia measurement using 18F-FMISO-PET (hypoxic volume and tumor/muscle ratio). Baseline measurement.
timeFrame: 18F-FMISO-PET between 1 and 3 weeks before the commencement of radio-chemotherapy
measure: Change from baseline tumor hypoxia using 18F-FMISO-PET (hypoxic volume and tumor/muscle ratio) during SCS.
timeFrame: 2nd 18F-FMISO-PET between 1 and 7 days after the 1st 18F-FMISO-PET
Secondary outcomes:
measure: Correlation between 18F-FMISO-PET values and pathological tumor parameters
timeFrame: Week 0 (at the commencement of radio-chemotherapy).
measure: Correlation with Karnofsky scale.
timeFrame: At 0, 2 and 9 months after the commencement of the radio-chemotherapy.
measure: Correlation with the ECOG (Eastern Cooperative Oncology Group) performance status scale
timeFrame: At 0, 2 and 9 months after the commencement of the radio-chemotherapy
measure: Correlation with the Quality of Life Questionnaire QLQ-C30 (EORTC)
timeFrame: At 0, 2 and 9 months after the commencement of the radio-chemotherapy.
measure: Overall survival.
timeFrame: At 9 months after the commencement of the radio-chemotherapy.
measure: Radiological response to treatment
timeFrame: 9 months after the commencement of radio-chemotherapy
measure: Radiological location of tumor relapse or progression
timeFrame: 9 months after the commencement of radio-chemotherapy
Other outcomes:
measure: Blood flow in carotid and middle cerebral arteries
timeFrame: Between 1 and 3 weeks before the commencement of radio-chemotherapy
measure: Facial and supraciliar infrared emission
timeFrame: Between 1 and 3 weeks before the commencement of radio-chemotherapy
Locations:
city: Las Palmas
country: Spain
facility: Dr. Negrin University Hospital
city: Madrid
country: Spain
facility: Instituto Tecnologico Servicios Sanitarios, in MD Anderson Cancer Center, Madrid
Study officials:
affiliation: Dr. Negrin University Hospital, Las Palmas
name: Bernardino Clavo, MD, PhD
role: STUDY_CHAIR
affiliation: Dr. Negrin University Hospital, Las Palmas
name: Bernardino Clavo, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Dr. Negrin University Hospital, Las Palmas
name: Francisco Robaina, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Instituto Tecnologico Servicios Sanitarios, in MD Anderson Cancer Center, Madrid
name: Juan C Alonso, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.