Feasibility of a Molecular Characterisation Approach to Treatment (FOrMAT)

FOrMAT - Feasibility of a Molecular Characterisation Approach to Treatment

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.

Study Overview

• Status: Unknown
• Conditions: Advanced Gastrointestinal Cancers

• Study Type: Observational
• Enrollment (Anticipated): 200

Contacts and Locations

• Study Contact: Name: Dr. Naureen Starling, BSc, MBBS, MRCP; Phone Number: +44 (0)208 661 3156; Email: naureen.starling@rmh.nhs.uk
• Study Contact Backup: Name: Annie Woodburne, BSc, MSc; Phone Number: +44 (0)208 661 3807; Email: annie.woodburne@rmh.nhs.uk

Study Locations

• United Kingdom
  • London and Surrey, United Kingdom, SM 25PT
    • Recruiting
    • The Royal Marsden NHS Foundation Trust
    • Contact: Annie Woodburne, MSc, BSc; Phone Number: +44 (0)208 661 3807; Email: annie.woodburne@rmh.nhs.uk
    • Principal Investigator: Dr. Naureen Starling, BSc, MBBS, MRCP
    • Sub-Investigator: Dr. Sing Yu Moorcraft, MB BCh, MRCP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Locally advanced or metastatic gastrointestinal cancer (including gastroesophageal, pancreatic, biliary tract and colorectal cancer)

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Targeted genetic sequencing of tumour specimen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The percentage of patients in whom a currently actionable molecular alteration was detected by genetic sequencing.	18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The concordance of results obtained from genetic sequencing compared to standard clinically validated techniques.		18 months
The proportion of patients in whom genetic sequencing was successfully performed.		18 months
The percentage of patients with a currently actionable genetic alteration who received targeted therapy as a result of genetic sequencing.	To assess the potential impact of genetic sequencing results on patients' treatment	18 months
Evaluation of the time required to obtain genetic sequencing results to see if genetic sequencing could be practically incorporated into clinical practice.	To assess whether genetic sequencing results can be obtained within a clinically meaningful timeframe	18 months
The proportion of screened patients who decide to participate in the trial and their reasons for participation or deciding not to participate.		18 months
The concordance of results obtained from core biopsy versus fine needle aspirate specimens from individual patients.		18 months
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.		18 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response rate for patients who received a targeted treatment as a result of genetic sequencing.		18 months
Overall survival of patients who received targeted treatment.		18 months
Evaluation of any changes in molecular markers at the time of disease progression or response to those from previous specimens.	To examine tumour heterogeneity in patients with paired specimens	18 months
Description of the microRNA expression profile of gastrointestinal tumours		18 months
Evaluation of any changes in circulating tumour DNA at the time of progression or response in comparison to previous specimens		18 months
Duration of response for patients who received a targeted treatment as a result of genetic sequencing.		18 months

Collaborators and Investigators

• Sponsor: Royal Marsden NHS Foundation Trust
• Investigators: Principal Investigator: Dr. Naureen Starling, BSc, MBBS, MRCP, Royal Marsden NHS Foundation Trust

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: February 1, 2014
• Primary Completion (Anticipated): August 1, 2015

Study Registration Dates

• First Submitted: March 31, 2014
• First Submitted That Met QC Criteria: April 9, 2014
• First Posted (Estimate): April 11, 2014

Study Record Updates

• Last Update Posted (Estimate): April 17, 2014
• Last Update Submitted That Met QC Criteria: April 16, 2014
• Last Verified: April 1, 2014

More Information

Terms related to this study

• Keywords: gastrointestinal cancer; molecular profiling; genetic sequencing; personalised medicine
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Digestive System Neoplasms; Gastrointestinal Diseases; Gastrointestinal Neoplasms
• Other Study ID Numbers: CCR 3994