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Use of circulating tumor dna test to intensify post-operative treatment of patients with resected colon cancer.
EU CTIS ID: 2024-515152-20-00
What this study is testing
The primary objective of the part 1 of this trial is to assess the rate of ct-DNA clearance at the end of the adjuvant treatment with FOLFOXIRI versus FOLFOX/CAPOX in stage III or high-risk stage II colon cancer patients with positive ct-DNA after surgery. The primary objective of the target-driven part 1 of this trial is to assess the rate of ct- DNA clearance at the end of the adjuvant treatment with FOLFOX plus Trastuzumab and Tucatinib in stage III or high-risk stage II HER2+/RAS wt colon cancer patients with positive ct-DNA after surgery. The primary objective of the part 2 of this trial is to assess the rate of ct-DNA clearance at the end of post-adjuvant treatment with trifluridine/tipiracil versus observation in stage III or high-risk stage II colon cancer patients with positive ct-DNA after the end of a fluoropyrimidine and oxaliplatin-based adjuvant therapy.
- Therapeutic exploratory (Phase II)
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- Part 1 and target-driven part 1, adjuvant phase II study: Written informed consent to study procedures;
- 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.
- For patients eligible for protocol treatment, availability of formalin-fixed, paraffinembedded (FFPE) tumor tissue from the surgical specimen for translational analysis.
- 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;
You likely can't join if
- Part 1, adjuvant phase II study and Part 2, post-adjuvant phase II study: Any evidence of metastatic disease (radiological or pathological metastasis);
- 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.
See the full eligibility criteria
Who can join
- Part 1 and target-driven part 1, adjuvant phase II study: Written informed consent to study procedures;
- 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.
- For patients eligible for protocol treatment, availability of formalin-fixed, paraffinembedded (FFPE) tumor tissue from the surgical specimen for translational analysis.
- 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.
- Part 2, post-adjuvant phase II study: Written informed consent to study procedures;
- ≥ 18 years of age;
- 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.
- 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 ((only for patients who received adjuvant as per clinical practice and not in the Part 1 of the study).
- Positive ct-DNA after the end of adjuvant treatment (centrally laboratory assessment).
- ECOG PS ≤ 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, alkaline phosphatase ≤2.5 x UNL.
- Creatinine clearance ≥ 50 mL/min or serum creatinine ≤1.5 x UNL.
- Availability of formalin-fixed, paraffin-embedded (FFPE) tumor tissue from the surgical specimen for translational analyses (only for patients who received adjuvant as per clinical practice and not in the Part 1 of the study).
- 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.
- 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.
- 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). The blood sample should be collected 2-6 weeks after the surgery.
- Neutrophils ≥1.5 x 109/L, Platelets ≥100 x 109/L, Hgb ≥ 9 g/dl.
What rules you out
- Part 1, adjuvant phase II study and Part 2, post-adjuvant phase II study: Any evidence of metastatic disease (radiological or pathological metastasis);
- 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.
- For Target-driven Part 1 population only:Has 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 for subjects on study treatment.
- 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 and target-driven 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
The study team makes the final eligibility decision.
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 18-64 years, 65+ years. The study team makes the final eligibility decision.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.