Home › Trials › NCT05062889

Using circulating tumor DNA to enhance treatment for colon cancer patients after surgery

Exploiting Circulating Tumour DNA to Intensify the Postoperative Treatment of Stage III and High-risk Stage II Resected Colon Cancer Patients With Adjuvant FOLFOXIRI and/or Post-adjuvant Trifluridine/Tipiracil

Phase 2 Interventional Gruppo Oncologico del Nord-Ovest · NCT05062889

This study is testing if a stronger treatment plan can help colon cancer patients after surgery by checking their blood for cancer DNA to see if it leads to better outcomes.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment477 (estimated)
Ages18 Years to 75 Years
SexAll
SponsorGruppo Oncologico del Nord-Ovest Academic / other
Drugs / interventionschemotherapy, Trastuzumab, Tucatinib
Locations28 sites (San Giovanni Rotondo, Foggia and 27 other locations)
Trial IDNCT05062889 on ClinicalTrials.gov

What this trial studies

This study evaluates whether intensified adjuvant treatment with FOLFOXIRI can increase the rate of undetectable circulating tumor DNA (ct-DNA) in patients with resected stage II and III colon cancer. It includes two parts: the first part randomizes patients to receive either standard treatments (FOLFOX or CAPOX) or the intensified FOLFOXIRI regimen based on ct-DNA status. The second part assesses the effectiveness of Trifluridine/Tipiracil in patients with positive ct-DNA after initial treatment. Additionally, a cohort of HER2-positive RAS wild-type colon cancer patients will receive a tailored treatment regimen including Trastuzumab and Tucatinib.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-75 with histologically confirmed stage II or III colon cancer who have undergone curative surgery and have positive ct-DNA post-surgery.

Not a fit: Patients with non-resectable colon cancer or those who do not meet the specific ct-DNA criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could lead to improved disease-free survival rates for high-risk colon cancer patients.

How similar studies have performed: Other studies have shown promise in using ct-DNA for treatment personalization, but this specific approach is novel.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria, Part I, adjuvant phase:

* Written informed consent to study procedures;
* 18 - 70 years of age ECOG Performance Status ≤ 1 or 71-75 years of age with ECOG Performance Status 0;
* Histologically confirmed stage III or high-risk stage II adenocarcinoma of colon including intraperitoneal rectal cancer. Stage II colon cancers are defined at high risk if at least one major prognostic factor (pT4, less than 12 nodes examined, clinical presentation with bowel perforation) or at least two minor prognostic factors (grade 3 or 4, clinical presentation with bowel obstruction, histological signs of vascular or lymphatic or perineural invasion, high preoperative CEA levels) are reported;
* Curative surgery performed no less than 4 and no more than 12 weeks prior to randomization (pending results of ct-DNA analysis, up to 2 cycles of FOLFOX/CAPOX are allowed to start the adjuvant treatment within 8-10 weeks after surgery);
* Contrast-enhanced chest and abdominal CT scan (or abdomen MRI and chest CT if contrast-enhanced CT scan is contraindicated) performed after the surgery and prior to randomization with no evidence of metastatic disease;
* Availability of formalin-fixed, paraffin-embedded (FFPE) tumor tissue from the surgical specimen and blood sample for ct-DNA analysis within 28 days prior randomization;
* Positive ct-DNA after surgery (central assessment);
* Neutrophils ≥1.5 x 109/L, Platelets ≥100 x 109/L, Hgb ≥ 9 g/dl;
* Total bilirubin ≤1.5 fold the upper-normal limits (UNL), ASAT (SGOT) and/or ALAT (SGPT) ≤2.5 x UNL (or \<5 x UNL in the case of liver metastases), alkaline phosphatase ≤2.5 x UNL (or \<5 x UNL in case of liver metastases);
* Creatinine clearance ≥50 mL/min or serum creatinine ≤1.5 x UNL;
* Women of childbearing potential must have a negative blood pregnancy test at the screening visit. For this trial, women of childbearing potential are defined as all women after puberty, unless the participants are postmenopausal for at least 12 months, are surgically sterile, or are sexually inactive. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient;
* Subjects and their partners must be willing to avoid pregnancy during the trial. Male subjects with female partners of childbearing potential and female subjects of childbearing potential must, therefore, be willing to use adequate contraception.

Contraception, starting during study screening visit throughout the study period up to 180 days after the last dose of chemotherapy. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject;

- Will and ability to comply with the protocol.

Inclusion Criteria Part 1 and target-driven part 1, adjuvant phase II study

* Written informed consent to study procedures;
* 18 - 70 years of age ECOG PS ≤ 1 or 71-75 years of age with ECOG PS 0;
* Histologically confirmed stage III or high-risk stage II adenocarcinoma of colon including intraperitoneal rectal cancer. Stage II colon cancers are defined at high risk if at least one major prognostic factor (pT4, less than 12 nodes examined, clinical presentation with bowel perforation) or at least two minor prognostic factors (grade 3 or 4, clinical presentation with bowel obstruction, histological signs of vascular or lymphatic or perineural invasion, high preoperative CEA levels) are reported;
* For target-driven Part 1 only: HER2+ and RAS wt disease as determined by a tissue-based assay (central laboratory assessment);
* Curative surgery performed no less than 4 and no more than 12 weeks prior to randomization (pending results of ct-DNA analysis, up to 2 cycles of FOLFOX/CAPOX are allowed to start the adjuvant treatment within 8-10 weeks after surgery);
* Contrast-enhanced chest and abdominal CT scan (or abdomen MRI and chest CT if contrast-enhanced CT scan is contraindicated) performed after the surgery and prior to randomization with no evidence of metastatic disease;
* Availability of formalin-fixed, paraffin-embedded (FFPE) tumor tissue from the surgical specimen and blood sample for ct-DNA analysis within 28 days prior randomization;
* Positive ct-DNA after surgery (central assessment);
* Neutrophils ≥1.5 x 109/L, Platelets ≥100 x 109/L, Hgb ≥ 9 g/dl;
* Total bilirubin ≤1.5 fold the upper-normal limits (UNL), ASAT (SGOT) and/or ALAT (SGPT) ≤2.5 x UNL, alkaline phosphatase ≤2.5 x UNL;
* Creatinine clearance ≥50 mL/min or serum creatinine ≤1.5 x UNL;
* For target-driven Part 1 only: Left ventricular ejection fraction (LVEF) ≥50% as assessed by echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scan.
* Availability of formalin-fixed, paraffin-embedded (FFPE) tumor tissue from the surgical specimen for translational analysis (only for patients eligible for protocol treatment);
* Women of childbearing potential must have a negative blood pregnancy test at the screening visit. For this trial, women of childbearing potential are defined as all women after puberty, unless they are postmenopausal for at least 12 months, are surgically sterile, or are sexually inactive. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient;
* Subjects and their partners must be willing to avoid pregnancy during the trial. Male subjects with female partners of childbearing potential and female subjects of childbearing potential must, therefore, be willing to use adequate contraception. Contraception, starting during study screening visit throughout the study period up to 180 days after the last dose of chemotherapy. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject;
* Will and ability to comply with the protocol.

Inclusion Criteria, Part II, post-adjuvant phase:

* Written informed consent to study procedures;
* ≥ 18 years of age;
* Histologically confirmed stage III or high-risk stage II adenocarcinoma of colon including intraperitoneal rectal cancer. Stage II colon cancers are defined at high risk if at least one major prognostic factor (pT4, less than 12 nodes examined, clinical presentation with bowel perforation) or at least two minor prognostic factors (grade 3 or 4, clinical presentation with bowel obstruction, histological signs of vascular or lymphatic or perineural invasion, high preoperative CEA levels) are reported;
* Fluoropyrimidine and oxaliplatin-containing adjuvant treatment for at least 3 months (6 cycles of 5-fluorouracil and oxaliplatin-based therapy or 4 cycles of capecitabine and oxaliplatin-based-therapy) and no more than 6 months (12 cycles of 5-fluorouracil and oxaliplatin-based therapy or 8 cycles of capecitabine and oxaliplatin-based-therapy);
* Contrast-enhanced chest and abdominal CT scan (or abdomen MRI and chest CT if contrast-enhanced CT scan is contraindicated) performed within 4 weeks from the end of adjuvant therapy and 28 days prior to randomization;
* Availability of FFPE tumor tissue from the surgical specimen and blood sample for ct-DNA analysis within 28 days prior to randomization;
* Positive ct-DNA after the end of adjuvant treatment (centrally laboratory assessment);
* ECOG Performance Status ≤ 1;
* Neutrophils ≥1.5 x 109/L, Platelets ≥100 x 109/L, Hgb ≥9 g/dl;
* Total bilirubin ≤1.5 fold the upper-normal limits (UNL), ASAT (SGOT) and/or ALAT (SGPT) ≤2.5 x UNL (or \<5 x UNL in the case of liver metastases), alkaline phosphatase ≤2.5 x UNL (or \<5 x UNL in case of liver metastases);
* Creatinine clearance ≥ 50 mL/min or serum creatinine ≤1.5 x UNL;
* Women of childbearing potential must have a negative blood pregnancy test at the screening visit. For this trial, women of childbearing potential are defined as all women after puberty, unless the participants are postmenopausal for at least 12 months, are surgically sterile, or are sexually inactive. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient;.
* Subjects and their partners must be willing to avoid pregnancy during the trial. Male subjects with female partners of childbearing potential and female subjects of childbearing potential must, therefore, be willing to use adequate contraception.

Contraception, starting during study screening visit throughout the study period up to 180 days after the last dose of chemotherapy. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject;

- Will and ability to comply with the protocol.

Exclusion Criteria:

* Part 1, adjuvant phase and Part 2, post-adjuvant phase
* Any evidence of metastatic disease (radiological or pathological metastasis);
* Macroscopic or microscopic evidence of residual tumor (R1 or R2 resections) after surgery;
* Other co-existing malignancies or malignancies diagnosed within the last 5 years with the exception of localized basal and squamous cell carcinoma or cervical cancer in situ;
* For Part 1 only: patient with complete dihydropyrimidine dehydrogenase (DPYD) deficiency (homozygous of the following DPYD polymorphisms: c1679GG, c1905+1AA, c2846TT);
* History or evidence upon physical examination of CNS disease unless adequately treated;
* Clinical signs of malnutrition;
* Active uncontrolled infections or other clinically relevant concomitant illness contraindicating chemotherapy administration;
* Evidence of bleeding diathesis or coagulopathy;
* Clinically significant (i.e. active) cardiovascular disease for example cerebrovascular accidents (≤6 months), myocardial infarction (≤6 months), unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication;
* Significant vascular disease (i.e. aortic aneurysm requiring surgical repair or recent arterial thrombosis) within 6 months of study enrolment;
* Lack of physical integrity of the upper gastrointestinal tract, malabsorption syndrome, or inability to take oral medication;
* Treatment with any investigational drug within 30 days prior to enrolment or 2 investigational agent half-lives (whichever is longer);
* Known hypersensitivity to trial drugs or hypersensitivity to any other component of the trial drugs;
* Any concomitant drugs contraindicated for use with the trial drugs according to the product information of the pharmaceutical companies;
* Pregnant or lactating women. Women of childbearing potential with either a positive or no pregnancy test at screening. Sexually active males and females (of childbearing potential) unwilling to practice contraception (as defined in section 5.5) during the study and until 180 days after the last trial treatment.
* Part 1, target-driven, adjuvant phase:
* Ongoing ≥ Grade 2 diarrhea of any etiology at screening;
* Presence of known chronic liver disease;
* Known to be positive for hepatitis C infection (positive by polymerase chain reaction \[PCR\]). Subjects who have been treated for hepatitis C infection are permitted if they have documented sustained virologic response of at least 12 weeks.
* Known to be positive for hepatitis B (HBV) by surface antigen (HBsAg) expression. Subjects who are positive for either hepatitis B surface antibody (HBsAB) or antibodies to the hepatitis B core antigen (HBcAB) should be screened using PCR measurement of hepatitis B DNA levels. Subjects with hepatitis B DNA levels by PCR that require nucleoside analogue therapy are not eligible for the trial. The latest local guidelines should be followed regarding the monitoring of hepatitis B DNA levels by PCR subjects on study treatment.

Where this trial is running

San Giovanni Rotondo, Foggia and 27 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Stage II Colon CancerStage III Colon CancerHER2-positive Colon CancerRAS Wild-type Colon CancerCirculating tumor DNAFOLFOXCAPOXFOLFOXIRI
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.