Epidemiological Study to Monitor Study Participants With Resected Stage II (High Risk) or Stage III Colorectal Cancer for Circulating Tumor DNA Before, During and After Their Treatment With Adjuvant Chemotherapy

• ClinicalTrials.gov Identifier: NCT04813627
• Recruitment Status: Recruiting
• First Posted: March 24, 2021
• Last Update Posted: April 11, 2024
• Sponsor: BioNTech SE
• Information provided by (Responsible Party): BioNTech SE

Tracking Information

• First Submitted Date: March 17, 2021
• First Posted Date: March 24, 2021
• Last Update Posted Date: April 11, 2024
• Actual Study Start Date: July 2, 2021
• Estimated Primary Completion Date: July 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 22, 2021)

• Occurrence of ctDNA positivity in the post-surgery/pre-AdCTx blood sample [ Time Frame: 4 to 8 weeks after surgery and within 7 days prior up to the day of start of AdCTx ]
  Blood sample taken post-surgery and pre-adjuvant chemotherapy.
• Occurrence of ctDNA positivity in the first post-AdCTx blood sample [ Time Frame: 14 to 21 days after last AdCTx treatment ]
  Blood sample taken post-adjuvant chemotherapy.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: March 22, 2021)

Transfer of participants from the BNT000-001 study to the BNT122-01 clinical trial [ Time Frame: 4 weeks following Visit 1 (upon availability of ctDNA positivity status) ]

The absolute and relative frequency of participants that will transfer to the BNT122-01 clinical trial from this epidemiological study will be reported.

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

Descriptive Information

• Brief Title: Epidemiological Study to Monitor Study Participants With Resected Stage II (High Risk) or Stage III Colorectal Cancer for Circulating Tumor DNA Before, During and After Their Treatment With Adjuvant Chemotherapy
• Official Title: Epidemiological Study to Determine the Prevalence of ctDNA Positivity in Participants With Stage II (High Risk) or Stage III CRC After Surgery With Curative (R0) Intent and Subsequent Adjuvant Chemotherapy With Monitoring of ctDNA During Clinical Follow-up

Brief Summary

This is a multi-site epidemiological study designed to monitor circulating tumor DNA (ctDNA) status in participants with Stage II (high risk)/III colorectal cancer (CRC) following resection/prior to adjuvant chemotherapy (AdCTx), during the course of AdCTx and for a period of 630 days thereafter, according to CRC stages and disease characteristics.

Participants receive no therapeutic intervention as part of this study. This study will identify participants who might be potential candidates for the clinical trial BNT122-01 (NCT04486378), a study of RO7198457 after completion of standard AdCTx in this patient population. Based on the eligibility criteria for that trial, this study will identify participants with confirmed Stage II (high risk)/III CRC that are positive for ctDNA after resection and are therefore at high risk of disease recurrence to enrich the BNT122-01 study cohort. These participants will have the option to enter screening for BNT122-01 at Screening Visit 2 of that trial if they meet the eligibility criteria of BNT000-001 during screening. Data from the assessments from BNT000-001 will be carried across to the BNT122-01 trial where feasible.

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

Biospecimen

Retention:   Samples With DNA

Description:

• Blood and tumor tissue samples collected for ctDNA assessment will be destroyed when subsequent clinical validity and/or bridging studies to support the validation of ctDNA assay are completed (where the samples are not exhausted).
• Remaining biospecimens from a particular participant must be destroyed if the participant specifically requests that their archival specimens are destroyed upon their withdrawal from the study.
• Remaining archival tissue blocks will be returned to the site upon request or no later than the time of final closure of the study database, whichever occurs first. For participants who are not eligible for enrollment in study BNT122-01, remaining archival tissue blocks will be returned to the site no later than 6 months after eligibility determination.

• Sampling Method: Probability Sample
• Study Population: Participants with Stage II (high risk)/III CRC after resection (R0) and that are scheduled to receive AdCTx will be enrolled in this study.

Condition

• Colorectal Cancer Stage II
• Colorectal Cancer Stage III

Intervention

Procedure: Regular blood sample collection for ctDNA assessment

Blood samples for in vitro testing of ctDNA status will be drawn at study visits every three months

Study Groups/Cohorts

Participants with R0 resected Stage II (high risk) or Stage III CRC

The participants eligible for this epidemiological study are those with completely resected Stage II (high risk)/III CRC (per the American Joint Committee on Cancer (AJCC) 8th revised edition staging system) due to receive standard of care chemotherapy for at least 3 months following surgery.

Intervention: Procedure: Regular blood sample collection for ctDNA assessment

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: November 30, 2022): 1500
• Original Estimated Enrollment (submitted: March 22, 2021): 200
• Estimated Study Completion Date: July 2024
• Estimated Primary Completion Date: July 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Must have given informed consent indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study.
• Age ≥ 18 years old at time of signing the informed consent form.
• Ability to comply with the study protocol, in the investigator's judgment.

• Must have Stage II/Stage III rectal cancer or Stage II (high risk)/Stage III colon cancer per AJCC 2017 that has been surgically totally resected (R0 confirmed by pathology report). Stage II (high risk) colon cancer is defined as (any of):

  • T4
  • Grade ≥ 3
  • Clinical presentation with bowel obstruction or perforation
  • Histological signs of vascular, lymphatic or perineural invasion
  • < 12 nodes examined
• Adequate tumor material in formalin-fixed paraffin embedded (FFPE) blocks or as sectioned tissue (only upon approval by sponsor) must be available, preferably from resection. The specimen should be submitted along with an associated pathology report. Multiple samples may be provided as available, but priority should be given to tissue with the highest tumor content and lowest necrotic area.
• Intention to receive a standard of care adjuvant chemotherapy (AdCTx) within 8 weeks post-surgery, and be scheduled for at least 3 months of treatment (including rest days) according to the treating physician or investigator.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
• Adequate end-organ function.

Exclusion Criteria:

• Induction of neoadjuvant systemic therapy prior to resection of CRC.
• Prior systemic investigational therapy.

• Positive serology for hepatitis B (unless immune due to vaccination or resolved natural infection or unless passive immunization due to immunoglobulin therapy):

  • Positive test for antibodies to hepatitis B core antigens (anti HBc) and
  • Negative test for antibodies to hepatitis B surface antigens (anti HBs).
• Active hepatitis C virus (HCV) infection; participants who have completed curative antiviral treatment with HCV viral load below the limit of quantification by polymerase chain reaction (PCR) are allowed.
• Participant has a history of human immunodeficiency virus (HIV) antibody positivity, or tests positive for HIV at screening.
• Residual tumor classification following surgery other than R0 (microscopic margin-negative resection).

• Participants with known past or current malignancy other than inclusion diagnosis, except for:

  • Cervical carcinoma of Stage 1B or less.
  • Non-invasive basal cell or squamous cell skin carcinoma.
  • Non-invasive, superficial bladder cancer.
  • Prostate cancer with a current PSA level < 0.1 ng/mL.
  • Any curable cancer with a complete response (CR) of > 2 years duration.
• Participant has not started standard of care AdCTx within 8 weeks post-surgery.
• Participant has received less than 3 months (including rest days) of AdCTx treatment.
• Inadequate tumor material (either quality or quantity) to support circulating tumor DNA (ctDNA) analysis.
• Participants who have had prior splenectomy.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: BioNTech clinical trials patient information; +49 6131 9084 ext 0; patients@biontech.de

• Listed Location Countries: Belgium, Germany, Spain, United States

Administrative Information

• NCT Number: NCT04813627
• Other Study ID Numbers: BNT000-001
• Has Data Monitoring Committee: No

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

• Plan to Share IPD: No

• Current Responsible Party: BioNTech SE
• Original Responsible Party: Same as current
• Current Study Sponsor: BioNTech SE
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: BioNTech Responsible Person; BioNTech SE

• PRS Account: BioNTech SE
• Verification Date: April 2024