The SUMMIT Study: A Cancer Screening Study (SUMMIT)

• ClinicalTrials.gov Identifier: NCT03934866
• Recruitment Status: Active, not recruiting
• First Posted: May 2, 2019
• Last Update Posted: November 8, 2022
• Sponsor: University College, London
• Collaborators: GRAIL, LLC; University College London Hospitals
• Information provided by (Responsible Party): University College, London

Tracking Information

• First Submitted Date: April 26, 2019
• First Posted Date: May 2, 2019
• Last Update Posted Date: November 8, 2022
• Actual Study Start Date: April 8, 2019
• Estimated Primary Completion Date: August 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 2, 2020)

• To evaluate the performance of the cell-free nucleic acid (cfNA) signals measured using high-intensity sequencing (ultra-deep and ultra-broad) for the detection of invasive cancer and identification of tissue of cancer origin using a GRAIL blood test. [ Time Frame: 12 months ]
  Cancer incidence associated with screening test performance:

  • Sensitivity
  • False positive rate (1-specificity), specificity
  • Positive predictive value (PPV)
  • Negative predictive value (NPV)
• To examine the performance of delivering a Low-Dose Computed Tomography (LDCT) screening service using established measures of performance and risk prediction of lung cancers and other incidental findings (see the performance indicators measured below). [ Time Frame: 36 months ]
  Performance indicators that will be measured include the number of:

  • eligible participants who choose to have an LDCT.
  • characteristics of those who choose to have LDCT, e.g. age, sex, ethnicity, area-level deprivation score and smoking status.
  • people who have a baseline LDCT who attend at year 1 and also at year 2.
  • screen-detected cancers per 1000 screened
  • early stage screen-detected cancers per 1000 screened
  • late stage screen-detected cancers per 1000 screened
  • people referred for diagnostic investigations per 1000 screened
  • people who have a biopsy per 1000 screened
  • malignant and benign tumours detected
  • incidence per 1000 per year

Original Primary Outcome Measures (submitted: April 30, 2019)

Cancer Incidence [ Time Frame: First Year ]

Endpoints associated with screening service performance measures:

• number of screen-detected cancers per 1000 screened (and number needed to screen to detect 1 cancer)
• number of early stage screen-detected cancers per 1000 screened (and number needed to screen to detect 1 early stage cancer)
• number of people referred for diagnostic investigations per 1000 screened
• number of people who have a biopsy per 1000 screened
• the malignant:benign biopsy ratio
• incidence per 1000 per year

• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: The SUMMIT Study: A Cancer Screening Study
• Official Title: The SUMMIT Study: Cancer Screening Study With or Without Low Dose Lung CT to Validate a Multi-cancer Early Detection Test
• Brief Summary: The SUMMIT Study will enrol 13,000 participants in order to investigate how cancer screening can be improved and delivered. The SUMMIT Study has two main aims: the first is to clinically validate a blood test for detecting multiple cancers at an early stage. The second is to examine the feasibility of delivering a low-dose CT (LDCT) screening service for lung cancer to a high-risk population in North Central and East London.

Detailed Description

The SUMMIT Study is a prospective, observational, cohort study. Its aim is to clinically validate a blood test for the early detection of multiple types of cancer, and to deliver LDCT screening for lung cancer to an at-risk population.

SUMMIT plans to enrol 13,000 participants aged 55-77 years, from participating general practitioner (GP) practices in North Central and East London. The participants enrolled will be people who are at high-risk for lung cancer due to a significant smoking history based on validated risk scores.

Individuals with significant smoking histories will be offered a clinical Lung Health Check (LHC), which includes a brief respiratory consultation including questions about respiratory symptoms and medical history, smoking cessation advice and referral where required, and certain relevant clinical measurements (blood pressure, spirometry, height, and weight). Those persons who are eligible for participation based on specific validated risk scores may then be offered participation in the SUMMIT Study. Electronic informed consent will be obtained if they decide to take part. Consented participants will provide a blood sample, complete a confidential electronic questionnaire and have an LDCT scan at the same visit. Participants will be asked to return for two further annual visits, and some participants may return for additional scans if clinically indicated (nodule management).

If any LDCT result is suspicious for cancer, the participant will be referred to their local hospital (type 2 Site) via an urgent referral pathway to the relevant MDT. If a participant is diagnosed with lung cancer, that participant will no longer continue in the active/interventional part of the study but will be followed for clinical outcomes via the Type 2 site completion of eCRF and registry data. If the suspicious lesion is found to be benign, the participant can continue in the study.

There will be one randomisation round carried out during this study. All participants with a negative LDCT at the baseline visit who have not been diagnosed with lung cancer since that visit will return for an LHC at approximately 12 months. At the 12-month visit, this group will be randomised either to have an LDCT or no LDCT.

However, if an urgent referral was after the Y0 LDCT scan, the participant will not be included in the randomisation at Y1, and will receive LDCT at Y1 and Y2.

• Study Type: Observational
• Study Design: Observational Model: Cohort; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided

Biospecimen

Retention:   Samples With DNA

Description:

Blood samples will be taken at each visit and sent to GRAIL to clinically validate a blood test for detecting multiple cancers at an early stage. An additional blood sample will be collected for (and stored by) UCL for future research.

• Sampling Method: Non-Probability Sample
• Study Population: SUMMIT plans to enrol 13,000 participants, aged 55-77 years, from participating GP practices in north and east London who are at high-risk for lung cancer due to a significant smoking history.

Condition

• Cancer
• Lung Cancer

Intervention

Radiation: Low Dose CT scan

Low Dose chest CT scan conferring an equivalent radiation dose of less than 2 mSv to the average size patient. The study aims to keep most scans under 1 mSv (ultra-low dose), and all scans under 2 mSv.

Study Groups/Cohorts

Group A (LDCT)

25,000 individuals who are at high-risk for lung cancer due to a significant smoking history.

Participants will receive at least 1 LDCT scan at baseline.

Intervention: Radiation: Low Dose CT scan

• Publications *: Dickson JL, Bhamani A, Quaife SL, Horst C, Tisi S, Hall H, Verghese P, Creamer A, Prendecki R, McCabe J, Gyertson K, Bowyer V, El-Emir E, Cotton A, Mehta S, Bojang F, Levermore C, Mullin AM, Teague J, Farrelly L, Nair A, Devaraj A, Hackshaw A, Janes SM; SUMMIT consortium. The reporting of pulmonary nodule results by letter in a lung cancer screening setting. Lung Cancer. 2022 Jun;168:46-49. doi: 10.1016/j.lungcan.2022.04.009. Epub 2022 Apr 20.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: May 17, 2021): 13035
• Original Estimated Enrollment (submitted: April 30, 2019): 50000
• Estimated Study Completion Date: August 2030
• Estimated Primary Completion Date: August 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Individuals 55 to 77 years old at the time of GP data extraction, who meet either of the following criteria:

   1. USPSTF LDCT screening criteria: a history of at least 30 pack years of smoking and if a former smoker, have quit in the past 15 years; or
   2. PLCOm2012 6-year lung cancer risk of ≥1.3%
2. Capable of providing informed consent and willing to comply with all parts of the protocol

Exclusion Criteria:

Currently receiving treatment (e.g., chemotherapy, radiotherapy, watchful waiting) for an active cancer. If on adjuvant hormonal therapy can be included (e.g. for breast and prostate cancer).

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 55 Years to 77 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United Kingdom

Administrative Information

• NCT Number: NCT03934866
• Other Study ID Numbers: UCL/17/0050
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: University College, London
• Original Responsible Party: Same as current
• Current Study Sponsor: University College, London
• Original Study Sponsor: Same as current

Collaborators

• GRAIL, LLC
• University College London Hospitals

• Investigators: Not Provided
• PRS Account: University College, London
• Verification Date: November 2022