Clinical trial NCT02112357: Feasibility of a Molecular Characterisation Approach to Treatment
Official title: FOrMAT - Feasibility of a Molecular Characterisation Approach to Treatment
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Advanced Gastrointestinal Cancers
Keywords: molecular profiling
genetic sequencing
personalised medicine
gastrointestinal cancer
Lead sponsor: Royal Marsden NHS Foundation Trust
Sponsor class: OTHER
First posted: 2014-04-11
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Locally advanced or metastatic gastrointestinal cancer (including gastroesophageal, pancreatic, biliary tract and colorectal cancer)

Brief summary: This study will assess the feasibility of sequencing locally advanced/metastatic gastrointestinal cancers in real-time to enable future treatment stratification by molecular characteristics. Targeted next generation sequencing of a panel of genes will be performed on tumour specimens and results will be discussed at a Sequencing Tumour Board to establish if a patient is potentially suitable for a targeted therapy.


Eligibility criteria: Inclusion Criteria:

1. Locally advanced or metastatic gastrointestinal cancer (including oesophageal, oesophagogastric junction, gastric, pancreatic, biliary and colorectal cancers).
2. Histological or cytological confirmation of diagnosis of malignancy.
3. Patients must either:

   1. Have received at least one line of treatment for locally advanced/metastatic disease OR
   2. Be about to start/currently undergoing their first line of treatment for locally advanced/metastatic disease
4. 18 years of age and over .
5. Performance status less than or equal to 2.
6. Able to provide fully informed consent.
7. Patients must either:

   1. Have an available tumour specimen (FFPE or fresh frozen) from either the primary tumour or a metastasis. Metastatic samples may be from any site with the exception of bone. OR
   2. Have a site of disease which is amendable to biopsy

Exclusion Criteria:

* There are no specific exclusion criteria for this study.

Primary outcomes:
measure: The percentage of patients in whom a currently actionable molecular alteration was detected by genetic sequencing.
timeFrame: 18 months
Secondary outcomes:
measure: The concordance of results obtained from genetic sequencing compared to standard clinically validated techniques.
timeFrame: 18 months
measure: The proportion of patients in whom genetic sequencing was successfully performed.
timeFrame: 18 months
measure: The percentage of patients with a currently actionable genetic alteration who received targeted therapy as a result of genetic sequencing.
timeFrame: 18 months
measure: Evaluation of the time required to obtain genetic sequencing results to see if genetic sequencing could be practically incorporated into clinical practice.
timeFrame: 18 months
measure: The proportion of screened patients who decide to participate in the trial and their reasons for participation or deciding not to participate.
timeFrame: 18 months
measure: The concordance of results obtained from core biopsy versus fine needle aspirate specimens from individual patients.
timeFrame: 18 months
measure: The number needed to enroll into the trial to identify one patient with a targetable genetic alteration and the number needed to enroll into the trial to treat one patient with a targeted agent.
timeFrame: 18 months
Other outcomes:
measure: Response rate for patients who received a targeted treatment as a result of genetic sequencing.
timeFrame: 18 months
measure: Overall survival of patients who received targeted treatment.
timeFrame: 18 months
measure: Evaluation of any changes in molecular markers at the time of disease progression or response to those from previous specimens.
timeFrame: 18 months
measure: Description of the microRNA expression profile of gastrointestinal tumours
timeFrame: 18 months
measure: Evaluation of any changes in circulating tumour DNA at the time of progression or response in comparison to previous specimens
timeFrame: 18 months
measure: Duration of response for patients who received a targeted treatment as a result of genetic sequencing.
timeFrame: 18 months
Locations:
city: London and Surrey
country: United Kingdom
facility: The Royal Marsden NHS Foundation Trust
Study officials:
affiliation: Royal Marsden NHS Foundation Trust
name: Dr. Naureen Starling, BSc, MBBS, MRCP
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mansukhani S, Barber LJ, Kleftogiannis D, Moorcraft SY, Davidson M, Woolston A, Proszek PZ, Griffiths B, Fenwick K, Herman B, Matthews N, O'Leary B, Hulkki S, Gonzalez De Castro D, Patel A, Wotherspoon A, Okachi A, Rana I, Begum R, Davies MN, Powles T, von Loga K, Hubank M, Turner N, Watkins D, Chau I, Cunningham D, Lise S, Starling N, Gerlinger M. Ultra-Sensitive Mutation Detection and Genome-Wide DNA Copy Number Reconstruction by Error-Corrected Circulating Tumor DNA Sequencing. Clin Chem. 2018 Nov;64(11):1626-1635. doi: 10.1373/clinchem.2018.289629. Epub 2018 Aug 27.
citation: Moorcraft SY, Gonzalez de Castro D, Cunningham D, Jones T, Walker BA, Peckitt C, Yuan LC, Frampton M, Begum R, Eltahir Z, Wotherspoon A, Teixeira Mendes LS, Hulkki Wilson S, Gillbanks A, Baratelli C, Fotiadis N, Patel A, Braconi C, Valeri N, Gerlinger M, Rao S, Watkins D, Chau I, Starling N. Investigating the feasibility of tumour molecular profiling in gastrointestinal malignancies in routine clinical practice. Ann Oncol. 2018 Jan 1;29(1):230-236. doi: 10.1093/annonc/mdx631.