Clinical trial NCT03163732: Evaluation of the Added Value of a Large Molecular Profiling Panel Versus a Limited Molecular Profiling Panel in Advanced Solid Tumors.
Official title: A Multicentric, Prospective Cohort Study Aiming to Evaluate the Added Value of a Large Molecular Profiling Panel (Panel FoundationOne) Versus a Limited Molecular Profiling Panel (Panel CONTROL) in Advanced Solid Tumors.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Advanced Solid Tumor
Keywords: Solid tumor
Advanced tumor
Profiling panel
Lead sponsor: Centre Leon Berard
Sponsor class: OTHER
Collaborators: name: Roche Pharma AG
First posted: 2017-05-23
Enrollment: 341
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: * Arm A: Tumor-based genomics according to the 324 cancer-related genes Next Generation Sequencing (NGS) panel from Foundation One (FOne panel).
* Arm B: Tumor-based genomics according to the 87 cancer-related genes NGS panel performed at Centre Leon Berard "Unité de Caractérisation Tumorale" (CONTROL panel).

Both panels will be performed concomitantly for all patients using the same patient tumor specimen.
Primary purpose: DIAGNOSTIC

Brief summary: The PROFILER 02 program is a multicenter, randomized, prospective cohort study aiming to compare the clinical relevance of a large Next-generation sequencing (NGS) panel (FondationOne or FOne panel) versus a limited NGS panel (CONTROL or CTL panel) in patients with advanced solid tumors.

This study will allow adapting the therapeutic management of these patients, if needed, by giving them recommended therapies (commercialized or in ongoing clinical trials), based on the recommendations of the Molecular Tumor Board (MTB).

Detailed description: The genetic and immunologic profile of the tumor will be determined from archival or fresh collected tumor sample.

For each patient, the tumor genomics data will be reviewed, at time of documented progressive disease, independently by a dedicated MTB to make a recommendation of therapy for a given patient based on its molecular profile. First, the genomics data issued from the panel defined by the randomization will be reviewed and recommended therapy resulting from randomization will be revealed to the Investigator. If a recommended therapy can be identified, this therapy will be recommended.

If none recommended therapy can be identified, the 2nd panel performed will then be reviewed.

In case of confirmed clinical or radiological progression (at Investigator's discretion) and/or unacceptable toxicity as per Investigator judgment during the line of therapy recommended by the MTB, the results of the second panel will be reviewed by MTB. Based on all genomics data available (i.e. randomized and 2nd panels), the MTB will recommend other treatment options. All results will be disclosed to Investigator in order to offer other treatment options.

Eligibility criteria: Inclusion Criteria:

* Male or female patient aged ≥ 18 years at time of inform consent signature.
* Currently treated by a first or a second line of chemotherapy for their advanced cancer (local relapse or metastatic; Immunotherapies, Endocrine therapies and Targeted therapies are not considered as a line of chemotherapy).
* Histologically confirmed diagnosis of advanced (local relapse or metastatic), incurable solid tumors from any histological types (except those listed in exclusion criteria 3).
* I4. Availability of an adequate tumor sample to be sent imperatively to the CLB within 15 days after ICF signature by order of preference either (i1) a tumor archival FFPE block not older than 3 months prior to ICF signature or if not available :(ii2) a dedicated biopsy from one accessible lesion visible by medical imaging and accessible to percutaneous sampling with a diameter of at least 10 mm or if not feasible (3) an archival tumor sample (primary tumor or metastatic lesion) not older than 3 years at time of ICF signature. Quality (at least 20-30% of tumor cells) and quantity (sample size surface area \> 5mm2 and \> 90um depth) of the tumor sample have to be confirmed mandatorily within 7 days by a central pathological review before confirmation of inclusion.
* Patient's disease which is not susceptible to progress during the next 45 days following the ICF signature.
* Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-1.
* Adequate organ and marrow function based on a medical records (within 21 days before randomization) as defined below :

  * Hemoglobin ≥ 9.0 g/dL
  * Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
  * Platelets ≥ 100 x 109/L
  * Lymphocyte count ≥ 1 x 109/L
  * Serum creatinine CL \> 50 mL/min per 1.73m2 using MDRD or CKD-EPI
  * AST and ALT ≤ 2.5 Upper Limit Normal (ULN) (up to 5 ULN may be tolerated in case of liver metastases)
  * Serum bilirubin ≤ 1. 5 ULN (in the absence of Gilbert's syndrome).
* Patient should understand, sign, and date the written ICF prior to any protocol-specific procedures performed. Patient should be able and willing to comply with study visits and procedures as per protocol.
* Patient must be covered by a medical insurance.

Exclusion Criteria:

* Inability to take oral medication or significant nausea and vomiting, malabsorption, external biliary shunt, or significant bowel resection that would preclude adequate absorption of oral medication.
* Any clinically significant and/or uncontrolled medical disease that could compromise the patient's ability to tolerate an anti-cancer treatment and its procedures (these conditions include but are not limited to severely impaired lung function, active gastrointestinal tract ulceration, acute or chronic uncontrolled liver disease/or severe renal disease, uncontrolled diabetes, history of HIV infection/or active viral infection (HBV, HCV), history of organ allograft or patient taking immunosuppressive treatment).
* Patient with the following advanced cancers :

  * Cancer bearing one of the oncogenic driver mutation: Colorectal cancer : KRAS, NRAS, HRAS and BRAF/Lung cancer: ALK, EGFR, ROS or MET/Breast cancers : RH+ and/or HER2+
  * High-grade serous ovarian cancers platinum-sensitive,
  * Liposarcoma.
  * Melanoma: BRAF
* Patient with non assessable tumor sample.
* Patient already included in this study for a type of cancer, can't be included a second time for the same cancer or for any other type of cancer.
* Pregnant or breastfeeding woman

Primary outcomes:
measure: Compare the proportion of patients for whom a genomically identified recommended therapy could be initiated using the large NGS panel from FoundationOne versus the limited CONTROL panel.
timeFrame: 28 months
Secondary outcomes:
measure: Compare in the 2 randomization arms the number of patients with at least one actionable alteration.
timeFrame: 28 months
measure: Compare in the 2 randomization arms the proportion of patients for which a genomically identified recommended therapy is effectively initiated.
timeFrame: 28 months
measure: Describe in both arms the number of patients for whom a genomically identified recommended therapy was available but not initiated.
timeFrame: 28 months
measure: Evaluate proportion of patients who could have been initiated a recommended therapy considering only the INCa panel.
timeFrame: 28 months
measure: Progression-Free Survival (PFS)
timeFrame: 24 months
measure: Overall response Rate (ORR)
timeFrame: 24 months
measure: Duration of response (DoR)
timeFrame: 24 months
measure: Patient Quality Of Life
timeFrame: 12 months
measure: Perform a health economic evaluation
timeFrame: 12 months
measure: Perform a health economic evaluation
timeFrame: 12 months
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: Institut Bergonié
city: Clermont-Ferrand
country: France
facility: Centre Jean PERRIN
city: Dijon
country: France
facility: Centre Georges François LECLERC
city: Lille
country: France
facility: Centre Oscar Lambret
city: Lyon
country: France
facility: Centre Léon Bérard
city: Lyon
country: France
facility: Hôpital Privé Jean Mermoz
city: Marseille
country: France
facility: Institut Paoli Calmettes
city: Marseille
country: France
facility: AP-HM MARSEILLE - Hôpital Nord
city: Montpellier
country: France
facility: Institut cancer Montpellier - ICM
city: Paris
country: France
facility: Institut Curie
city: Paris
country: France
facility: Hopital Tenon
city: Rennes
country: France
facility: Centre Eugène Marquis
city: Saint-Herblain
country: France
facility: ICO site René Gauducheau
city: Saint-Priest-en-Jarez
country: France
facility: Institut de Cancérologie Lucien NEUWIRTH
city: Toulouse
country: France
facility: Institut Claudius Regaud
Study officials:
affiliation: Centre Leon Berard
name: Olivier Olivier, MD
role: PRINCIPAL_INVESTIGATOR
References: