Identification and Treatment Of Micrometastatic Disease in Stage III Colon Cancer

NCT03803553 | Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: 18-397
• Study Type: interventional
• Target: 400
• Locations: 1 country
• Sites: 3

Brief Summary

This research study is comparing two standard of care treatment options based on blood test results for participants who have metastatic colon cancer. The names of the potential treatments involved in this study are:

• Active surveillance
• FOLFIRI treatment
• Nivolumab treatment
• Encorafenib/Binimetinib/Cetuximab treatment
• Trastuzumab + Pertuzumab

Conditions

Stage III Colon Cancer; Metastatic Colon Cancer

Keywords

Metastatic colon Cancer; Stage III Colon Cancer

Outcome Measures

Primary Outcomes (2)

• Disease-free survival (DFS)

  Disease-free survival (DFS) between ctDNA-positive patients treated with additional treatment of FOLFIRI and ctDNA-positive patients who are untreated

  5 years

• Clearance rate of ctDNA

  Compare the clearance rate of ctDNA in ctDNA-positive patients between patients treated with additional treatment of FOLFIRI and those who are untreated

  7 Months

Secondary Outcomes (9)

• Overall Survival (OS) Rate

  5 years

• Clearance rate of ctDNA of Arm 4: Nivolumab Treatment

  13 months

• Disease-free survival (DFS) of Arm 4: Nivolumab Treatment

  5 years

• Clearance rate of ctDNA of Arm 5: Encorafenib/Binimetinib/Cetuximab Treatment

  7 months

• Disease-free survival (DFS) of Arm 5: Encorafenib/Binimetinib/Cetuximab Treatment

  5 years

Study Arms (6)

ctDNA-POSITIVE: FOLFIRI Protocol

EXPERIMENTAL

Pre-screening evaluation, including tumor assessment, tumor sequencing and blood tests. If these tests show that the participant is eligible to participate in the research study . The participant will be randomized into 1 of 3 groups : ctDNA-Positive: Folfiri or ctDNA-Positive: Active Surveillance or ctDNA Negative: Active Surveillance \- ctDNA-POSITIVE: FOLFIRI Protocol * FOLFIRI chemotherapy via intravenous infusion on days 1-3 of each cycle. Cycle is 14 days long. This will occur for up to 12 cycles (24 weeks). * infusions will consist of the drugs * 5-Fluorouracil * Irinotecan * Leucovorin

Drug: FOLFIRI Protocol

ctDNA-POSITIVE: ACTIVE SURVEILLANCE

ACTIVE COMPARATOR

Pre-screening evaluation, including tumor assessment, tumor sequencing and blood tests. If these tests show that the participant is eligible to participate in the research study . The participant will be randomized into 1 of 3 groups : ctDNA-Positive: Folfiri or ctDNA-Positive: Active Surveillance or ctDNA Negative: Active Surveillance \-- Active surveillance. * Observation and monitoring with imaging (every 3 months), tumor markers, and ctDNA draws every 1 month for the initial 6 months. * After 6 months, followed with ctDNA, tumor markers, and scans every 3 months for the first 3 years and every 6 months thereafter. Additional scans and tumor markers will be at the discretion of the clinician. .

Other: ACTIVE SURVEILLANCE

ctDNA-NEGATIVE: ACTIVE SURVEILLANCE

ACTIVE COMPARATOR

Pre-screening evaluation, including tumor assessment, tumor sequencing and blood tests. If these tests show that the participant is eligible to participate in the research study . The participant will be randomized into 1 of 3 groups : ctDNA-Positive: Folfiri or ctDNA-Positive: Active Surveillance or ctDNA Negative: Active Surveillance \- Observation and monitoring with imaging, tumor markers, and ctDNA collections every 3 months for the first 3 years and every 6 months thereafter. Additional scans and tumor markers will be at the discretion of the clinician

Other: ACTIVE SURVEILLANCE

ctDNA-POSITIVE MSI-H: NIVOLUMAB

EXPERIMENTAL

Pre-screening evaluation, including tumor assessment, tumor sequencing and blood tests. If these tests show that the participant is eligible to participate in the research study and is ctDNA positive and MSI-H, the participant will not be randomized and will be placed into the group: ctDNA positive, MSI-H: Nivolumab -ctDNA-Positive, MSI-H: Nivolumab Protocol * Nivolumab treatment via intravenous infusion on day 1 of each cycle. Cycle is 28 days long. This will occur for up to 12 cycles (48 weeks). * infusions will consist of the drug Nivolumab

Drug: Nivolumab Protocol

ctDNA-POSITIVE BRAF Mutant: ENCORAFENIB/BINIMETINIB/CETUXIMAB

EXPERIMENTAL

Pre-screening evaluation, including tumor assessment, tumor sequencing and blood tests. If these tests show that the participant is eligible to participate in the research study and is ctDNA positive and has a BRAF mutation, the participant will not be randomized and will be placed into the group: ctDNA positive, BRAF mutant: Encorafenib/Binimetinib/Cetuximab -ctDNA-Positive, MSI-H: Encorafenib/Binimetinib/Cetuximab Protocol * Encorafenib/Binimetinib treatment is received orally every day and Cetuximab via intravenous infusion on day 1 of each cycle. Cycle is 14 days long. This will occur for up to 12 cycles (24 weeks). * infusions will consist of the drug Cetuximab

Drug: Encorafenib/Binimetinib/Cetuximab Protocol

6 Months Additional Trastuzumab and Pertuzumab

EXPERIMENTAL

Pre-screening evaluation, including tumor assessment, tumor sequencing and blood tests. Participants that are eligible to receive Trastuzumab and Pertuzumab will be placed in this HER2 cohort: ctDNA-positive \& HER2 amplification and MSS Trastuzumab and Pertuzumab. Trastuzumab is received via intravenous administration, and Pertuzumab treatment is received intravenously by infusion. Cycle is 21 days. This will occur for up to 8 cycles.

Drug: Trastuzumab + Pertuzumab

Interventions

Nivolumab Protocol DRUG

Nivolumab cycle will be four weeks (28 days) long, with Nivolumab administered on day 1. Participants will receive up to 12 four-week cycles (for a total of 48 weeks) of Nivolumab treatment.

Also known as: Nivolumab

ctDNA-POSITIVE MSI-H: NIVOLUMAB

Encorafenib/Binimetinib/Cetuximab Protocol DRUG

Encorafenib/Binimetinib will be taken orally every day and Cetuximab will be administered intravenously on day 1 of each cycle. Cycles are 14 days long. Participants will receive up to 12 two-week cycles (for a total of 24 weeks) of Encorafenib/Binimetinib/Cetuximab.

Also known as: Enco/Bini/Cetux

ctDNA-POSITIVE BRAF Mutant: ENCORAFENIB/BINIMETINIB/CETUXIMAB

Trastuzumab + Pertuzumab DRUG

Trastuzumab (Herceptin) is received by intravenous administration and Pertuzumab is received intravenously by infusion on Day 1 of each cycle. Cycles are 21 days long. Participants will receive up to 8 cycles of Trastuzumab and Pertuzumab.

Also known as: Herceptin

6 Months Additional Trastuzumab and Pertuzumab

FOLFIRI Protocol DRUG

FOLFIRI cycle will be two weeks (14 days) long, with FOLFIRI administered on Days 1-3. Participants will receive up to 12 two-week cycles (for a total of 24 weeks) of FOLFIRI chemotherapy.

Also known as: FOLinic acid-Fluorouracil-IRInotecan regimen

ctDNA-POSITIVE: FOLFIRI Protocol

ACTIVE SURVEILLANCE OTHER

Will be followed with observation and monitoring with imaging, tumor markers, and ctDNA collections

ctDNA-NEGATIVE: ACTIVE SURVEILLANCE; ctDNA-POSITIVE: ACTIVE SURVEILLANCE

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must have histologically confirmed resected Stage III adenocarcinoma of the colon. Any T \[Tx, T1, T2, T3, or T4-\], N1-2M0.
• Participants must have completely resected disease. In patients with tumor adherent to adjacent structures, en block RO resection must be documented.
• Entire tumor must be in the colon (rectal involvement is excluded).
• Participants must have completed standard adjuvant chemotherapy per the discretion of the treating physician. Standard therapy includes FOLFOX, CAPOX, or therapy with 5FU analog alone will be permitted if it constitutes appropriate standard therapy in the opinion of the treating physician.
• Participants must not have received prior neoadjuvant chemotherapy.
• Age ≥18 years.
• ECOG performance status ≤1.
• Life expectancy of greater than 3 months.
• Participants must have normal organ and marrow function as defined below:
• leukocytes ≥3,000/mcL
• absolute neutrophil count ≥1,500/mcL
• platelets ≥100,000/ mcL
• total bilirubin within normal institutional limits. For patients with Gilbert's syndrome, total bilirubin must be ≤ 2 and documented as elevated indirect bilirubin.
• AST(SGOT)/ALT(SGPT) ≤3 (AST) or ≤ 3 (ALT) × institutional upper limit of normal
• creatinine within normal institutional limits OR

You may not qualify if:

• Patients who are receiving additional investigational therapy or on another investigational protocol
• Patients who have confirmed metastatic disease per CT.
• Patients who are unable to get any standard adjuvant therapy
• Patients who have received more than 6 months of standard adjuvant therapy at the time of study entry.
• With the exception of standard of care adjuvant therapy, patient received anticancer therapy including chemotherapy, immunotherapy, or antineoplastic biologic therapy (e.g., cetuximab, bevacizumab etc.), within 30 days prior to start of study treatment.
• Patients who are MSI-high or have a BRAF V600E mutation are excluded from Arm 1 (FOLFIRI) and Arm 2 (Active Surveillance).
• Patients with a BRAFV600E mutation and who are MSI-high are excluded from Arm 5 (ENCO/BINI/CETUX).
• Has uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• (ctDNA positive cohort only). Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 6 months for woman and 6 months for men, after the last dose of trial treatment.
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin and squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
• Has an active infection requiring systemic therapy.
• Must have documentation of microsatellite instability status. NGS, PCR based assessment and Immunohistochemistry (IHC) are acceptable. Presence of deficient (d) DNA mismatch repair (dMMR) may be assessed by IHC for MMR protein expression (MLH1, MSH2, MSH6, PMS2) where loss of one or more proteins indicated dMMR. This may be done locally.
• Patients must have detectable ctDNA (Guardant Reveal assay) post standard adjuvant therapy in order to be in this cohort.
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other forms of immunosuppressive therapy within 7 days prior to the first dose of nivolumab treatment. Subject requiring systemic steroids are excluded from the trial. The use of physiologic doses of corticosteroids may be approved after discussion with the sponsor.

Sponsors & Collaborators

• Stand Up To Cancer: collaborator
• Massachusetts General Hospital: lead

Study Sites (3)

Massachusetts General Hospital

Boston, Massachusetts, 02115, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

Weill Cornell Medical College

New York, New York, 10065, United States

RECRUITING

MeSH Terms

Conditions

Colonic Neoplasms

Interventions

IFL protocol; Watchful Waiting; Nivolumab; encorafenib; Trastuzumab; pertuzumab

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Outcome Assessment, Health Care; Outcome and Process Assessment, Health Care; Quality of Health Care; Health Services Administration; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Aparna Parikh, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Aparna Parikh, MD

CONTACT

617-724-4000; Aparna.Parikh@MGH.HARVARD.EDU

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 10, 2019
• First Posted: January 14, 2019
• Study Start: April 16, 2020
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027
• Last Updated: May 1, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: MGH - Contact the Partners Innovations team at http://www.partners.org/innovation

Locations

US (3)