Clinical Trials /

Identification and Treatment Of Micrometastatic Disease in Stage III Colon Cancer

NCT03803553

Description:

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

Related Conditions:
  • Colon Adenocarcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Identification and Treatment Of Micrometastatic Disease in Stage III Colon Cancer
  • Official Title: Early Identification and Treatment of Occult Metastatic Disease in Stage III Colon Cancer

Clinical Trial IDs

  • ORG STUDY ID: 18-397
  • NCT ID: NCT03803553

Conditions

  • Metastatic Colorectal Cancer
  • Stage III Colorectal Cancer

Interventions

DrugSynonymsArms
FOLFIRI ProtocolFOLinic acid-Fluorouracil-IRInotecan regimenctDNA-POSITIVE: FOLFIRI Protocol

Purpose

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

Detailed Description

      The FDA (the U.S. Food and Drug Administration) has approved FOLFIRI, comprised of
      Irinotecan, Leucovorin, and 5-Fluorouracil, as a treatment option for metastatic colorectal
      cancer in the Stage IV setting.

        -  After diagnosis and surgical removal of tumors, individuals with metastatic colorectal
           cancer commonly receive what is called adjuvant chemotherapy treatment, commonly
           utilizing treatment plans called FOLFOX, CAPOX, or therapy with 5-Fluorouracil.

        -  If all the cancer is not killed, the investigators may be able to detect tumor in the
           blood called circulating tumor DNA (ctDNA). This is genetic material unique to
           metastatic colorectal cancer that may be present in the blood stream, and it can be
           identified through a ctDNA blood test. If ctDNA is present in the blood stream, it is
           commonly called micro-metastatic disease (meaning disease that can't be seen detected by
           CT scans but may be there in the blood). Cancer researchers believe that ctDNA in the
           blood stream may be an indicator that cancer is more likely to recur.

        -  After initial adjuvant chemotherapy, it is standard for individuals to begin active
           surveillance, where they do not receive further treatment but instead undergo frequent
           tumor imaging scans to see if their cancer is stable, growing, or coming back. The
           investigators plan to see if additional therapy, where FOLFIRI (comprised of Irinotecan,
           Leucovorin, and 5-Fluorouracil) is administered can decrease recurrence. Typically,
           FOLFIRI is given when the disease is visibly recurrent.

      However, in this research study, the investigators are

        -  determining whether there are differences in cancer recurrence in ctDNA positive
           participants treated with additional therapy versus put on active surveillance.

        -  determining whether there are differences in health in ctDNA positive participants
           treated with additional therapy versus put on active surveillance.

        -  examining whether patients who undergo further therapy experience changes in the ctDNA
           levels.
    

Trial Arms

NameTypeDescriptionInterventions
ctDNA-POSITIVE: FOLFIRI ProtocolExperimentalPre-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 into1 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
  • FOLFIRI Protocol
ctDNA-POSITIVE: ACTIVE SURVEILLANCEActive ComparatorPre-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 into1 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. .
    ctDNA-NEGATIVE: ACTIVE SURVEILLANCEActive ComparatorPre-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 into1 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

      Eligibility Criteria

              Inclusion Criteria:
      
                -  Participants must have histologically confirmed resected Stage III adenocarcinoma of
                   colorectal. Any T [Tx, T1, T2, T3, or T4-], N1-2MO; included NC.
      
                -  Patient must have completed 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)
      
                -  Patients must have a plan to receive or must be receiving 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.
      
                -  Pre-screening must begin prior to or within the first 3 months of starting adjuvant
                   treatment.
      
                -  Patients must have a CT scan 3-6 weeks after completion of adjuvant therapy to confirm
                   no radiographic evidence of disease
      
                -  Patients must not have had 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
      
                     -  AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal creatinine within
                        normal institutional limits
      
                        --- OR
      
                     -  creatinine clearance ≥60 mL/min/1.73 m2 for participants with creatinine levels
                        above institutional normal.
      
                -  Women of childbearing potential (WOCBP) must use appropriate method(s) of
                   contraception. WOCBP should use an adequate method to avoid pregnancy for 6 months
                   after the last dose of investigational drug.
      
                -  Women of childbearing potential must have a negative serum or urine pregnancy test
                   (minimum sensitivity 25 IU/L or equivalent units of HCG).
      
                -  Women must not be breastfeeding
      
                -  Men who are sexually active with WOCBP must use any contraceptive method with a
                   failure rate of less than 1% per year.
      
                -  Women who are not of childbearing potential, ie, who are postmenopausal or surgically
                   sterile as well as azoospermic men, do not require contraception
      
                -  Must have documentation of microsatellite status. Immunohistochemistry (IHC) is
                   acceptable as is PCR. 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 per local standards.
      
                -  Patients must have sufficient tumor tissue available for molecular profiling, defined
                   as at least 10 x 5 micron sections of FFPE tumor tissue or the equivalent.
      
                -  Patients must have a detectable mutation on molecular profiling to be followed as per
                   guidelines below.
      
                   -- Tumor Sequencing:
      
                     -  DNA extracted from formalin-fixed or frozen primary tumor tissue will need to be
                        sequenced to identify somatic mutations across all or a subset of the coding
                        regions for at least 50 genes. Patients must have at least 1 mutation identified
                        on tumor sequencing that is covered by the ctDNA assay. Tumor sequencing will be
                        performed at Memorial Sloan Kettering by IMPACT.
      
                        -- Circulating tumor DNA (ctDNA) analysis:
      
                     -  DNA extracted from plasma will be assessed for the presence of mutations. Testing
                        may be performed using digital PCR or next-generation sequencing but must be able
                        to reliably identify genomic alterations (excluding copy number changes or
                        fusions) at or below a minimum allele frequency of 0.2%. If initial ctDNA assay
                        fails to meet minimum coverage levels patients will be excluded from the study.
                        Testing must be performed by ACCESS- Memorial Sloan Kettering Molecular Genetics
                        Laboratory, New York, NY.
      
                        -- Definition of ctDNA positive:
      
                     -  In order to be eligible for the ctDNA positive cohort, patient must be ctDNA
                        positive following adjuvant therapy. ctDNA positive will be defined as positive
                        if at least one mutation is shared between the tumor and ctDNA sequence. The
                        mutation(s) of interest can be assessed as changes at the nucleotide or protein
                        level (i.e. KRAS c.35G>A vs. KRAS G12D).
      
                -  The effects on the developing human fetus are unknown. For this reason and because
                   5FU, Capecitabine, Oxaliplatin, Irinotecan, and Leucovorin are known to be
                   teratogenic, women of child-bearing potential and men must agree to use adequate
                   contraception (hormonal or barrier method of birth control; abstinence) prior to study
                   entry and for the duration of study participation. Should a woman become pregnant or
                   suspect she is pregnant while she or her partner is participating in this study, she
                   should inform her treating physician immediately. Men treated or enrolled on this
                   protocol must also agree to use adequate contraception prior to the study, for the
                   duration of study participation, and 6 months after completion of any of the study
                   drug administration.
      
                -  Ability to understand and the willingness to sign a written informed consent document
      
              Exclusion Criteria:
      
                -  Patients who are receiving additional investigational therapy or on another
                   investigational protocol
      
                -  Patients who have confirmed metastatic disease.
      
                -  Patients who are unable to get any standard adjuvant therapy
      
                -  Patient who have received more than 3 months of standard adjuvant therapy at the time
                   of potential study entry
      
                -  Patients who are MSI-high are excluded
      
                -  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.
      
                -  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
            
      Maximum Eligible Age:N/A
      Minimum Eligible Age:18 Years
      Eligible Gender:All
      Healthy Volunteers:No

      Primary Outcome Measures

      Measure:Disease-free survival (DFS)
      Time Frame:5 years
      Safety Issue:
      Description:Disease-free survival (DFS) between ctDNA-positive patients treated treated with additional adjuvant therapy and ctDNA-positive patients who are untreated

      Secondary Outcome Measures

      Measure:Overall Survival (OS) Rate
      Time Frame:5 years
      Safety Issue:
      Description:Overall survival (OS) between ctDNA-positive patients treated with additional adjuvant therapy and ctDNA-positive patients who are untreated

      Details

      Phase:Phase 3
      Primary Purpose:Interventional
      Overall Status:Not yet recruiting
      Lead Sponsor:Massachusetts General Hospital

      Trial Keywords

      • Metastatic colorectal cancer
      • Stage III Colorectal Cancer

      Last Updated