Clinical trial NCT03133273: Study of the Therapeutic Response and Survival of Patients with Metastatic Colorectal Cancer (stage IV) and Treated According to the Guidelines of a Chemosensitivity Test, Oncogramme® (ONCOGRAM)
Official title: Study of the Therapeutic Response and Survival of Patients with Metastatic Colorectal Cancer (stage IV) and Treated According to the Guidelines of a Chemosensitivity Test, Oncogramme®
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Colorectal Cancer Metastatic
Chemotherapy
Keywords: Colorectal Cancer Metastatic
Chemosensitivity
Lead sponsor: University Hospital, Limoges
Sponsor class: OTHER
Collaborators: name: Oncomédics
First posted: 2017-04-28
Enrollment: 256
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Patients corresponding to the inclusion criteria and having a histologically proven metastatic CRC on biopsies or primary tumor excision and / or one or more metastatic sites will be recruited prospectively and randomized into two groups.

1. Usual care group: no Oncogramme will be made.
2. Oncogramme group: Taking of tumor fragments on the histological piece by an anatomopathological physician at the time of the histological examination and placing samples in the transport medium. The Oncogramme will be performed by Oncomedics on all specimens. Results will be returned to clinicians within 15 days.

For both groups, the adjuvant treatment will be decided in the multidisciplinary consultation meeting (MCM), according to the recommendations in force and adapted to the general medical condition of the patient. For patients in the Oncogramme group, chemotherapy will be adapted to Oncogramme.
Primary purpose: OTHER

Brief summary: Currently, chemotherapies are empirically administered to patients treated for colorectal cancer (CRC). Selection is based on the efficacy of a protocol previously determined on the largest number (consensus treatment), the decision-making process being weighted by patient's intrinsic criteria. However, each patient is unique, due to the inter- and intratumoral heterogeneity inherent in any cancer, partly explaining the unsatisfactory response rates observed for available chemotherapies. Functional sensitivity tests offer the possibility to adapt the treatment to each patient: they are based on an ex vivo study of the responses of the tumor cells (survival / death) to the different molecules / therapeutic combinations (chemotherapy or targeted therapy) likely to be administered to the patient. This response, translated into a tumor-specific sensitivity profile, can be used by the clinicians to determine the most appropriate therapeutic protocol. By increasing the therapeutic efficacy from the first line and reducing the deleterious side effects associated with multiple drug cycles, the sensitivity test transforms the consensus approach into personalized medicine, providing patients with improved progression free survival (PFS) associated with an improvement in the quality of life. Oncomedics has developed Oncogramme®, a CE-labeled in vitro diagnostic medical device that has already demonstrated the ability to predict chemosensitivity in a recent pilot study of metastatic CRC (prediction with 84% chance of success of tumor sensitivity to chemotherapy, vs. 50% maximum for chemotherapy administered according to the consensus method). The hypothesis that patients treated with a metastatic CRC for which systemic chemotherapy is adapted using Oncogramme® have better response rates, PFS and quality of life than patients treated according to usual practice, with optimization of the costs of care. To our knowledge, this is the only fully standardized test available, where each step and reagents of the procedure are mastered. The reliability of the procedure makes it possible to render a personalized result for each patient in 97% of the cases. In addition, the analysis is specifically centered on tumor cells using a method using fully defined, developed and validated media and reagents for each cancer, including CRC. The method of revealing the effect of the therapies identifies the proportion of dead cells in each condition, whatever their physiological state (proliferation / quiescence), by determining the percentage of living and killed cells, thus ensuring high sensitivity


Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 years
* Patient with metastatic colon or rectal adenocarcinoma (Stage IV) who can benefit from standard systemic chemotherapy (monotherapy based on 5-FU, polychemotherapy type FOLFOX, FOLFIRI, FOLFIRINOX, associated or not with targeted therapies Adapted to the expression of BRAF and RAS, whatever the route of administration of the proposed, oral or intravenous therapies)
* Metastatic CRC diagnosed preoperatively on imaging or per-operative on macroscopic findings and proved by histological analysis (biopsy or surgical excision and if possible biopsies or excrescence on the metastatic sites)
* Measurable metastases according to RECIST
* Chemotherapy for curative or palliative purposes
* Patient with consent.
* Affiliate or beneficiary of a social security scheme.

Exclusion Criteria:

* Formal contraindication to paraclinic exploration essential for patient follow-up
* Exclusive use of radiotherapy, targeted therapy, immunotherapy or hormone therapy, exclusive palliative support
* Patient with an absolute contraindication to the administration of chemotherapy
* Pregnant, lactating or non-contraceptive women for childbearing age women
* Patient with a difficulty of understanding the protocol
* Patient under protective measures (guardianship, curatorship, etc.).

Primary outcomes:
measure: Occurrence of the progression or death of the patient.
timeFrame: Year 1
Secondary outcomes:
measure: Response to first-line treatment administrated
timeFrame: every month, up to 12 months
measure: Overall survival
timeFrame: Month 6 and Year 1
measure: Specific survival
timeFrame: Month 6 and Year 1
measure: Incremental Cost / Efficiency Ratio
timeFrame: Year 1
measure: Incremental Cost / Utility Ratio
timeFrame: Year 1
measure: Quality of life
timeFrame: Month 3, Month 6, Month 9 and Year 1
measure: No adaptation of chemotherapy
timeFrame: every month, up to 12 months
measure: Grade 3 and higher adverse events related to chemotherapy
timeFrame: Year 1
Other outcomes:
Locations:
city: Amiens
country: France
facility: CHU d'AMIENS
city: Bordeaux
country: France
facility: Bergonié Institut
city: Brive-la-Gaillarde
country: France
facility: Clinique des Cédres
city: Chambray-lès-Tours
country: France
facility: CHU de TOURS
city: Clermont-Ferrand
country: France
facility: Clermont-Ferrand University Hospital
city: Fort-De-France
country: France
facility: CHu de la Martinique
city: Guéret
country: France
facility: Hospital Center
city: Limoges
country: France
facility: Limoges University Hospital
city: Nîmes
country: France
facility: Nimes University Hospital
city: Poitiers
country: France
facility: CHU de POITIERS
city: Saint-Junien
country: France
facility: CH de Saint Junien
city: Sainte-Feyre
country: France
facility: Centre Médical MGEN Alfred Leune
city: Strasbourg
country: France
facility: CHU de Strasbourg
Study officials:
affiliation: University Hospital, Limoges
name: Muriel Mathonnet, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mathonnet M, Vanderstraete M, Bounaix Morand du Puch C, Giraud S, Lautrette C, Ouaissi M, Tabchouri N, Taibi A, Martin R, Herafa I, Tchalla A, Christou N; ONCOGRAM trial investigators. ONCOGRAM: study protocol for the evaluation of therapeutic response and survival of metastatic colorectal cancer patients treated according to the guidelines of a chemosensitivity assay, the Oncogramme(R). Trials. 2021 Aug 21;22(1):556. doi: 10.1186/s13063-021-05531-y.