Clinical trial NCT02802969: Improvement of Local Control in Skull Base, Spine and Sacral Chordomas Treated by Surgery and Protontherapy Targeting Hypoxic Cells Revealed by [18F]FAZA) PET/CT Tracers
Official title: Improvement of Local Control in Skull Base, Spine and Sacral Chordomas Treated by Surgery and Protontherapy Targeting Hypoxic Cells Revealed by [18F]FAZA) PET/CT Tracers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Skull Base Chordoma
Vertebral Chordoma
Lead sponsor: Institut Curie
Sponsor class: OTHER
First posted: 2016-06-16
Enrollment: 64
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Improved local control of chordoma initially treated with surgery or not, thanks to adjuvant radiotherapy oriented by conventional imaging Computed Tomography /Magnetic Resonance Imaging (CT / MRI) and guided by the \[18Fluor\] (\[18F\]) Fluoroazomycin Arabinofuranoside (FAZA) Positron Emission Tomography / Computed Tomography (PET / CT) to target the radioresistant hypoxic cells.

Detailed description: Due to the close contacts of the lesion with the neurovascular structures, in the case of skull base chordoma and mobile spine, surgery is often incomplete. On the contrary, surgery of the sacral region (for which the block excision is often possible) brings a better therapeutic outcome. Radiotherapy with high-dose supplement improves the outcomes for all these lesions.

Intratumoral hypoxia is a primary factor of radioresistance, it's known since long by radiation oncologists. \[18F\]FAZA gives an image of the hypoxic volume target. Investigators propose to increase the radioactive dose in the hypoxic volume target but in order to succeed, radiation oncologists have to precisely identify this hypoxic volume. Radiation oncologists would increase of 10% the radioactive dose that will allow us to improve local control at 3 years of 15% without any additional side effect.

Eligibility criteria: Inclusion Criteria:

* Typical chordoma and chondroid chordoma of the skull base, spine or chordoma of sacral region
* Patient undergoing an additional or exclusive radiotherapy (Photontherapy and/or Prothontherapy)
* Age ≥ 18 years old
* ECOG performance status 0 to 2
* Satisfying biological functions 28 days before inclusion :

  1. Haemoglobin ≥ 9 g/dL
  2. Neutrophils ≥ 1500/mm3
  3. Platelets ≥ 100 000/mm3
  4. ASAT, ALAT, GGT, PAL ≤ 1.5 N, bilirubin ≤ 40 μmol/L, LDH ≤ 1.5 N
  5. Creatininemia \< 1.5 N
* Satisfying vital cardiac and respiratory functions
* Neurologic functions well stabilised
* Effective contraception for women of childbearing age during the the protontherapy treatment and during the month following the end of treatment. A pregnancy test shall be negative at inclusion.
* Patient covered by health insurance
* Patient provided with information and signature of informed consent.

Exclusion Criteria:

* Dedifferentiated chordomas, chondrosarcoma
* History of cancer (except cutaneous basocellular epithelioma or epithelioma of the uterine cervix) having recurred in the 5 years preceding entry in the trial and no relapse in the last 3 years
* Metastatic patient
* History of brain radiation therapy, or base of the skull or spinal segments to be treated
* Contraindications to radiotherapy
* Contraindications to PET/CT examinations \[18F\] Fluorodexoxyglucose (FDG) and \[18\]FAZA
* Associated pathology likely to prevent the patient from receiving treatment,
* Incompatible treatment with the inclusion in the study (oxygen therapy, EPO, anti-vascular treatments, anti-angiogenic treatments)
* Patient already included in another therapeutic trial with an experimental medication,
* Patient currently nursing,
* Persons deprived of their liberty, or under guardianship,
* Impossibility of undergoing the trial's medical follow-up for geographical, social or psychological reasons.

Primary outcomes:
measure: Improvement local control of chordomas according to RECIST criteria.
timeFrame: 36 months
measure: Improvement local control of chordomas according to PERCIST criteria
timeFrame: 36 months
Secondary outcomes:
Other outcomes:
Locations:
city: Saint-Cloud
country: France
facility: Institut Curie - Hôpital René Huguenin
state: Ile de France
Study officials:
affiliation: Institut Curie
name: Hamid MAMMAR, MD
role: PRINCIPAL_INVESTIGATOR
References: