PROSPECT-C: A Study of Biomarkers of Response or Resistance to Anti-EGFR Therapies in Metastatic Colorectal Cancer

Metastatic Colorectal Cancer Clinical Trial

— PROSPECT-C  

Official title:

PROSPECT-C: A Prospective Translational Study Investigating Molecular Predictors of Resistance and Response to Cetuximab or Panitumumab in Metastatic Colorectal Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02994888
• Other study ID #: 3770
• Status: Completed
• Phase: N/A
• First received: May 30, 2013
• Last updated: December 16, 2016
• Start date: November 2012
• Est. completion date: December 2016

Study information

• Verified date: December 2016
• Source: Royal Marsden NHS Foundation Trust
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Research Ethics Committee
• Study type: Observational

Clinical Trial Summary

PROSPECT-C is a phase II study investigating the molecular markers of response or resistance to anti-epidermal growth factor receptor (EGFR) antibodies.

Description:

Cetuximab or panitumumab are two monoclonal antibodies that are routinely offered to patients with metastatic colorectal cancer when they have no mutation in RAS genes. In Royal Marsden Hospital patients, who are refractory to all standard therapies and have metastatic colorectal cancer are offered one of these agents in third line metastatic setting. Whilst the mechanisms of response/resistance to these therapies are well studies, they are still incompletely understood. The main hypothesis of this study is that finding mechanisms of response and/or resistance by using novel techniques such as next generation sequencing (NGS) and/or digital droplet polymerase chain reaction (ddPCR) to these therapies will allow better patient selection and application of precision medicine in such patients.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 47
• Est. completion date: December 2016
• Est. primary completion date: December 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. patients with a histologically confirmed diagnosis of metastatic colorectal adenocarcinoma

2. wild-type RAS tumour status by molecular analysis at the Royal Marsden Hospital

3. patients with inoperable metastatic colorectal cancer who are scheduled to be treated with cetuximab (or panitumumab) either as monotherapy or in combination with chemotherapy with palliative intent

4. patients who have received prior treatment with oxaliplatin, irinotecan and fluoropyrimidine containing chemotherapy regimens OR intolerance/contraindication to either oxaliplatin or irinotecan based chemotherapy, and planned to receive retreatment with EGFR monoclonal antibody (mAB) monotherapy or with EGFR mAB combined with a chemotherapy (irinotecan or oxaliplatin-based) that a patient has already received for a minimum of 3 months during a previous line of therapy.

5. patients who have metastatic disease sites which are amenable to core biopsy (preferably liver, soft tissue or nodal disease, with at least one lesion 3cm or more in diameter. If largest lesion 2-3cm diameter, eligibility to be discussed with radiologist prior to study entry)

6. patients aged 18 years or older

7. able to provide fully informed consent, to comply with the trial and follow-up procedures

8. receiving treatment at the Royal Marsden Hospital

Exclusion Criteria:

1. patients who have previously received treatment with cetuximab or panitumumab

2. previous malignancy other than colorectal cancer in the past 5 years, other than pre-invasive malignancy of the cervix or basal cell carcinoma, EXCEPT when the patient has histological confirmation of metastatic colorectal cancer at the site that is planned to be biopsied at baseline and on progression of disease

3. patients who are being anti-coagulated with warfarin or heparin

4. Patients that are participating in another clinical trial involving an investigational medicinal product, unless it is more than 14 days after they have ceased the investigational medicinal product

5. Patients that are participating in another research study involving tumour tissue biopsies planned to take place during the time that the patient is participating in this study

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Metastatic Colorectal Cancer

Intervention

Drug:
• Cetuximab
All patients will be offered cetuximab 500mg/m2 every 2 weeks, until the time of progression

Locations

Country	Name	City	State
United Kingdom	The Royal Marsden NHS Foundation Trust	Surrey	Sutton

Sponsors (1)

Lead Sponsor	Collaborator
Royal Marsden NHS Foundation Trust

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Track and validate specific known mechanisms of resistance/response to anti-EGFR therapies through	digital droplet polymerase chain reaction (ddPCR) and ultra deep next generation sequencing (NGS) analyses of circulating tumour deoxyribonucleic acid (ct-DNA) obtained every 4 weeks during the course of treatment. Mutations found in ctDNA will also be analysed in the archival and fresh tissue specimens, used for diagnostic testing and obtained during the study respectively	3-4 years	No
Secondary	Identify novel biomarkers of resistance to anti-EGFR therapies through whole exome sequencing	DNA extracted from pre- and post-treatment metastatic colorectal cancer (mCRC) biopsies; Ultra deep targeted sequencing of tumour samples and of ctDNA will be used to assess whether the identified resistance biomarkers are detectable in some patients before treatment initiation and whether this correlates with short progression free survival (PFS) and poor radiological response	3-4 years	No