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

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ClinicalTrials.gov Identifier: NCT02994888
Recruitment Status : Completed
First Posted : December 16, 2016
Last Update Posted : December 19, 2016
Sponsor:
Information provided by (Responsible Party):
Royal Marsden NHS Foundation Trust

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

Condition or disease Intervention/treatment
Metastatic Colorectal Cancer Drug: Cetuximab

Detailed 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.

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Study Type : Observational
Actual Enrollment : 47 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: PROSPECT-C: A Prospective Translational Study Investigating Molecular Predictors of Resistance and Response to Cetuximab or Panitumumab in Metastatic Colorectal Cancer
Study Start Date : November 2012
Actual Primary Completion Date : December 2016
Actual Study Completion Date : December 2016

Resource links provided by the National Library of Medicine

Drug Information available for: Cetuximab

Group/Cohort Intervention/treatment
all patients
All patients will be treated with cetuximab 500mg/m2 every 2 weeks until the time of progression
Drug: Cetuximab
All patients will be offered cetuximab 500mg/m2 every 2 weeks, until the time of progression




Primary Outcome Measures :
  1. Track and validate specific known mechanisms of resistance/response to anti-EGFR therapies through [ Time Frame: 3-4 years ]
    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


Secondary Outcome Measures :
  1. Identify novel biomarkers of resistance to anti-EGFR therapies through whole exome sequencing [ Time Frame: 3-4 years ]
    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


Biospecimen Retention:   Samples With DNA

Both fresh frozen tissue and formalin-fixed paraffin-embedded (FFPE) tissue samples will be obtained. In addition, the following blood samples will also be taken;

  1. Baseline: an initial 20mL research blood sample (EDTA or equivalent (CPT) tube) will be collected
  2. Every 4 weeks until disease progression or patient death: 1 x 10mL research blood sample (EDTA or equivalent (CPT) tube) will be collected
  3. At time of progressive disease: final 10mL research blood sample (EDTA or equivalent (CPT) tube)


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
patients with a histologically confirmed diagnosis of metastatic colorectal adenocarcinoma
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02994888


Locations
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United Kingdom
The Royal Marsden NHS Foundation Trust
Surrey, Sutton, United Kingdom, SM2 5PT
Sponsors and Collaborators
Royal Marsden NHS Foundation Trust

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Responsible Party: Royal Marsden NHS Foundation Trust
ClinicalTrials.gov Identifier: NCT02994888     History of Changes
Other Study ID Numbers: 3770
First Posted: December 16, 2016    Key Record Dates
Last Update Posted: December 19, 2016
Last Verified: December 2016
Additional relevant MeSH terms:
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Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Cetuximab
Antineoplastic Agents, Immunological
Antineoplastic Agents