## Protocol Section
### Identification Module
**NCT ID:** NCT04367779

**Acronym:** PROTONBIOMARKS

**Brief Title:** Research of Biomarkers of Response to Proton Beam Therapy in Pediatric and Adult Patients.

**Official Title:** PROTONBIOMARKS - Research of Biomarkers of Response to Proton Beam Therapy in Pediatric and Adult Patients: A Genomic, Epigenetic, and Immunological Analysis

#### Organization Study ID Info
**ID:** ET19-284
#### Organization
**Class:** OTHER
**Full Name:** Centre Leon Berard
### Status Module
#### Completion Date
**Date:** 2024-06

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2023-09-13

**Type:** ACTUAL

**Last Update Submit Date:** 2023-09-12

**Overall Status:** RECRUITING

#### Primary Completion Date
**Date:** 2024-06

**Type:** ESTIMATED

#### Start Date
**Date:** 2020-09-24

**Type:** ACTUAL

**Status Verified Date:** 2023-09

#### Study First Post Date
**Date:** 2020-04-29
**Type:** ACTUAL
**Study First Submit Date:** 2020-04-24
**Study First Submit QC Date:** 2020-04-28
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Centre Leon Berard

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** This trial is a paucicentric, clinico-biological cohort study with retrospective and prospective enrollment, aiming to identify biomarkers predictive of response to Proton Beam Therapy (PBT) in cancer patients (high grade sarcoma, brain tumors and meningioma). This study include collection of clinical data, of tumor samples (collected during standard of care) and a blood sample for alive patients.

**Detailed Description:** The proton beam model policy adopted by the American Society of Radiation Oncology (ASTRO) in 2017 supports proton therapy in primary solid neoplasms in children treated with curative intent. To date, PBT is also recognised in adults as a valid option providing life expectancy \> 10 years, for inoperable axial or head and neck sarcomas, low grade brain tumors (i.e. low grade astrocytoma, oligodendroglioma and ependymoma), non-operated meningioma of skull base and other rare clinical situations (re-irradiation, locally aggressive tumor malignant or not arising in sites which preclude R0 or R1 surgical resection). Recently, Jhaveri et al. have reported the retrospective analysis of a National Cancer Data Base (NCDB) and shown an improved overall survival in adult Grade I-IV glioma patients treated with PBT versus patients treated with radiotherapy (XRT). Positive impact on toxicity free survival and general health status of patients were reported in others indications. centers join their expertise (pediatric, brain and sarcoma cancers for Centre Léon Bérard (CLB) and protons for CAL) and their recruitment to optimize the treatment strategy for these patients.

The Centre Leon Bérard recently reported on the ProfilER protocol (NCT01774409). It is the largest molecular characterization program in France with now over 4000 patients included. It enabled to identify genomic biomarkers of radio resistance. In this context, the investigator's proposal is to conduct a genomic, epigenetic, and immunological analysis of patients treated with proton beam therapy with the aim to identify Biomarkers of response to PBT in pediatric and adult patients.

### Conditions Module

**Conditions:**

- Brain Cancer

- Meningioma

- Sarcoma

**Keywords:**

- Proton Beam Therapy

- Biomarkers

- Pediatric and adult cancers

- Proton Therapy

### Design Module

#### Bio Spec

**Description:** Tumor sample(s) (FFPE and/or Frozen) from primary tumor (biopsy or surgery specimen) Blood sample (only for alive patients) collected at the time of PBT initiation or during any clinical exam performed after validation of inclusion

**Retention:** SAMPLES_WITH_DNA

#### Design Info

**Observational Model:** COHORT

**Time Perspective:** OTHER

#### Enrollment Info

**Count:** 100

**Type:** ESTIMATED

**Study Type:** OBSERVATIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Pediatric and adult patients with High Grade Sarcoma treated or to be treated with Proton Beam Therapy (PBT) and not candidate to surgery before PBT.

**Label:** A : High Grade Sarcoma

#### Arm Group 2

**Description:** Pediatric and adult patients with Brain Tumors treated or to be treated with Proton Beam Therapy (PBT) and not candidate to surgery before PBT.

**Label:** B : Brain tumors

#### Arm Group 3

**Description:** Pediatric and adult patients with Meningioma treated or to be treated with Proton Beam Therapy (PBT) and not candidate to surgery before PBT.

**Label:** C : Meningioma

### Outcomes Module

#### Primary Outcomes

**Description:** Correlation between local tumor response according to RECIST 1.1 criteria and expression of biomarkers defined by using different techniques (HTG, WES, RNAseq, IHC)

**Measure:** Identify predictive biomarkers for local response at 6 months after the end of Proton Beam Therapy

**Time Frame:** At 6 months after the end of Proton Beam Therapy

#### Secondary Outcomes

**Description:** Correlation between local tumor response according to RECIST 1.1 criteria and expression of biomarkers defined by using different techniques (HTG, WES, RNAseq, IHC)

**Measure:** To identify predictive biomarkers for clinical outcomes

**Time Frame:** At 12 months and at 24 months after the end of Proton Beam Therapy

**Description:** Correlation between progression free survival and expression of biomarkers expression of biomarkers defined by using different techniques (HTG, WES, RNAseq, IHC)

**Measure:** To identify predictive biomarkers for clinical outcomes

**Time Frame:** From the start of Proton Beam Therapy until the date of the first documented progression or date of death from any cause, whichever came first, assessed up to 48 months

**Description:** Correlation between overall survival and expression of biomarkers defined by using different techniques (HTG, WES, RNAseq, IHC)

**Measure:** To identify predictive biomarkers for clinical outcomes

**Time Frame:** From the start of Proton Beam Therapy until the date of death from any cause, assessed up to 48 months

**Description:** Correlation between radiation related toxicity (only Adverse Event (AE) Grade ≥3) according to NCI-CTCAE V5.0. and expression of biomarkers defined by using different techniques (HTG, WES, RNAseq, IHC)

**Measure:** To identify predictive biomarkers for clinical outcomes

**Time Frame:** From the start of Proton Beam Therapy until at least 24 months after the end of Proton Beam Therapy

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* I1 Male or female patients, all ages are eligible.
* I2 Confirmed diagnosis of macroscopic tumor previously treated since 2016 (retrospective cohort) or to be treated (prospective cohort) with PBT including one of the following tumor types:Cohort A : high grade sarcoma ; Cohort B: brain tumors; Cohort C: meningioma.
* I3 Presence of at least one measurable lesion before PBT initiation. Post operative situation is possible providing a measurable macroscopic residue, non candidate to a new surgery before PBT.
* I4 Availability of archival representative formalin-fixed, paraffin-embedded (FFPE) and/or frozen tumor sample, with the corresponding hematoxylin and eosin stained slide and a pathological report, meeting the following quality/quantity control (QC) criteria confirmed by a central pathological review: (this sample will be also used to confirm pathological diagnosis ) : at least 20% of tumor cells and a surface area \> 5mm2 with \> 90μm of depth.
* I5. Performance status before PBT: Lansky Play score for pediatric patients \< 12 years of age ≥ 70%; Karnofsky performance status for pediatric patients ≥ 12 years of age ≥ 70%; PS ECOG for adult patients: 0, 1 or 2.
* I6. For prospective cohort : Life-expectancy before PBT \> 2 years .
* I7. For prospective cohort : Women of child-bearing potential and men must agree to use (must have used for retrospective cohort) adequate contraception during all the radiotherapy procedure
* I8. For alive patients - Written informed consent from patient, parents if applicable/legal representative, before any study-specific screening procedures, and willingness to comply to study visits and procedures.

Exclusion Criteria:

* E1. Patients previously treated with radiotherapy in the same site (re-irradiation), either with protons or photons
* E2. Pregnant or breast-feeding patients at time of PBT initiation.

**Sampling Method:** NON_PROBABILITY_SAMPLE

**Sex:** ALL

**Standard Ages:**

- CHILD

- ADULT

- OLDER_ADULT

**Study Population:** Alive or Dead cancer patients with high grade sarcoma, brain tumors or meningioma Previously treated with PBT since 2016 (Retrospective cohort) or Patients to be treated with PBT (Prospective cohort)

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** gwenaelle.garin@lyon.unicancer.fr

**Name:** Gwenaële Garin

**Phone:** + 33 (0)4 78 78 28 28

**Role:** CONTACT

**Contact 2:**

**Email:** line.claude@lyon.unicancer.fr

**Name:** Claude Line

**Phone:** + 33 (0)4 78 78 28 28

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Lyon

**Contacts:**

***Contact 1:***

- **Email:** line.claude@lyon.unicancer.fr

- **Name:** Claude Line

- **Phone:** +33(0)4 78 78 28 28

- **Role:** CONTACT

***Contact 2:***

- **Name:** SUNYACH Marie-Pierre

- **Role:** SUB_INVESTIGATOR

***Contact 3:***

- **Name:** GREGOIRE Vincent

- **Role:** SUB_INVESTIGATOR

***Contact 4:***

- **Name:** TANGUY Ronan

- **Role:** SUB_INVESTIGATOR

***Contact 5:***

- **Name:** POMMIER Pascal

- **Role:** SUB_INVESTIGATOR

**Country:** France

**Facility:** Centre Léon Bérard

**Status:** RECRUITING

**Zip:** 69008

**Location 2:**

**City:** Nice

**Contacts:**

***Contact 1:***

- **Email:** pierre-yves.bondiau@nice.unicancer.fr

- **Name:** BONDIAU Pierre

- **Phone:** 04 92 03 12 72

- **Role:** CONTACT

***Contact 2:***

- **Name:** DOYEN Jérôme

- **Role:** SUB_INVESTIGATOR

**Country:** France

**Facility:** Centre Antoine Lacassagne

**Status:** RECRUITING

**Zip:** 06189

#### Overall Officials

**Official 1:**

**Affiliation:** Centre Leon Berard

**Name:** Claude Line

**Role:** PRINCIPAL_INVESTIGATOR

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000009370

- Term: Neoplasms by Histologic Type

- ID: D000009369

- Term: Neoplasms

- ID: D000009380

- Term: Neoplasms, Nerve Tissue

- ID: D000009383

- Term: Neoplasms, Vascular Tissue

- ID: D000008577

- Term: Meningeal Neoplasms

- ID: D000016543

- Term: Central Nervous System Neoplasms

- ID: D000009423

- Term: Nervous System Neoplasms

- ID: D000009371

- Term: Neoplasms by Site

- ID: D000009422

- Term: Nervous System Diseases

- ID: D000001927

- Term: Brain Diseases

- ID: D000002493

- Term: Central Nervous System Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: All

- Name: All Conditions

- Abbrev: BC10

- Name: Nervous System Diseases

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M15327

- Name: Sarcoma

- Relevance: LOW

- As Found: Unknown

- ID: M5209

- Name: Brain Neoplasms

- Relevance: HIGH

- As Found: Brain Cancer

- ID: M11562

- Name: Meningioma

- Relevance: HIGH

- As Found: Meningioma

- ID: M12315

- Name: Neoplasms by Histologic Type

- Relevance: LOW

- As Found: Unknown

- ID: M12325

- Name: Neoplasms, Nerve Tissue

- Relevance: LOW

- As Found: Unknown

- ID: M12328

- Name: Neoplasms, Vascular Tissue

- Relevance: LOW

- As Found: Unknown

- ID: M11560

- Name: Meningeal Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M18937

- Name: Central Nervous System Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M12367

- Name: Nervous System Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M5204

- Name: Brain Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M5742

- Name: Central Nervous System Diseases

- Relevance: LOW

- As Found: Unknown

- ID: T5284

- Name: Soft Tissue Sarcoma

- Relevance: LOW

- As Found: Unknown

- ID: T3707

- Name: Meningioma

- Relevance: HIGH

- As Found: Meningioma

### Condition Browse Module - Meshes

- ID: D000008579

- Term: Meningioma

- ID: D000001932

- Term: Brain Neoplasms

### Misc Info Module

- Version Holder: 2024-05-24
