Exploiting Circulating Tumour DNA to Intensify the Postoperative Treatment Resected Colon Cancer Patients
- Conditions
- Stage II Colon CancerStage III Colon CancerHER2-positive Colon CancerRAS Wild-type Colon Cancer
- Interventions
- Drug: L-Leucovorin
- Registration Number
- NCT05062889
- Lead Sponsor
- Gruppo Oncologico del Nord-Ovest
- Brief Summary
The aims of this study are to evaluate if an intensified adjuvant treatment with FOLFOXIRI could increase the rate of cases with undetectable ct-DNA after chemotherapy and to evaluate if a further adjuvant treatment with Trifluridine/Tipiracil could increase the rate of cases with undetectable ct-DNA and therefore improve DFS in a population at high-risk of relapse.
An additional target-driven cohort of HER2+ RAS wild-type colon cancer patients will be assessed for ct-DNA clearance after a tailored treatment with Trastuzumab and Tucatinib plus FOLFOX
- Detailed Description
This is a prospective, open-label, multicentre study, including two phase II randomized trials. In Part 1 resected stage III and high-risk stage II colon cancer patients with positive ct- DNA after surgery will be randomized to receive FOLFOX for 12 cycles or CAPOX for 8 cycles (at investigator choice) versus FOLFOXIRI for 12 cycles.
In Part 1 target-driven resected stage III and high-risk stage II HER2+ and RAS wild-type colon cancer patients with positive ct-DNA after surgery will receive Trastuzumab and Tucatinib plus FOLFOX for 12 cycles.
In Part 2 resected stage III and high-risk stage II colon cancer patients with positive ct- DNA after the end of a fluoropyrimidine and oxaliplatin-based adjuvant therapy - either in the frame or outside of Part 1 - will be randomized to receive observation or Trifluridine/Tipiracil for 6 cycles.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 477
Not provided
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Arm B FOLFOXIRI, part 1 (adjuvant) L-Leucovorin FOLFOXIRI Irinotecan 165 mg/sqm iv over 60 minutes day 1, followed by Oxaliplatin 85 mg/sqm iv over 2 hours day 1, in two-way with L-Leucovorin 200 mg/sqm iv over 2 hours, day 1 followed by 5-fluoruracil 3200 mg/sqm 48 h-continuous infusion, starting on day 1; to be repeated every 2 weeks for a maximum of 12 cycles. In the case of oxaliplatin and/or irinotecan interruption because of adverse events, patient's refusal or investigator's choice, the continuation of the other drugs until 12 cycles is recommended. Arm A mFOLFOX6 or CAPOX (at investigator's choice), part 1 (adjuvant) L-Leucovorin mFOLFOX6 Oxaliplatin 85 mg/sqm iv over 2 hours, day 1 in two-way with L-Leucovorin 200 mg/sqm iv over 2 hours, day 1 followed by 5-fluorouracil 400 mg/sqm iv bolus, day 1 followed by 5-fluoruracil 2400 mg/sqm 48 h-continuous infusion, starting on day 1; to be repeated every 2 weeks for a maximum of 12 cycles. The continuation of 5FU/leucovorin until 12 cycles is recommended also if oxaliplatin is interrupted because of adverse events, patient's refusal or investigator's choice. CAPOX Oxaliplatin 130 mg/sqm iv over 2 hours, day 1; Capecitabine 1000 mg/sqm/bid per os from day 1 to day 14; to be repeated every 3 weeks until 8 cycles. The continuation of Capecitabine until 8 cycles is recommended also if oxaliplatin is interrupted because of adverse events, patient's refusal or investigator's choice. Pending the results of ct-DNA analysis, up to 2 cycles of FOLFOX/CAPOX before randomization are allowed to start the adjuvant treatment within 8-10 weeks after surgery Trastuzumab and Tucatinib plus mFOLFOX6, part 1 target-driven (adjuvant) L-Leucovorin Tucatinib 300 mg (two 150 mg tablets)/bid orally twice daily (approximately 8 to 12 hours between doses with or without a meal); Trastuzumab 4 mg/kg iv over 30 minutes, day 1 (loading dose: 6 mg/kg iv over 90 minutes), followed by mFOLFOX6 Oxaliplatin 85 mg/sqm iv over 2 hours, day 1 in two-way with L-Leucovorin 200 mg/sqm iv over 2 hours, day 1 followed by 5-fluorouracil 400 mg/sqm iv bolus, day 1 followed by 5-fluoruracil 2400 mg/sqm 48 h-continuous infusion, starting on day 1; to be repeated every 2 weeks for a maximum of 12 cycles. In the case of oxaliplatin and/or trastuzumab and/or tucatinib interruption because of adverse events, patient's refusal or investigator's choice, the prosecution of the other drugs until 12 cycles is recommended. Pending the results of ct-DNA analysis, up to 2 cycles of FOLFOX/CAPOX before randomization are allowed to start the adjuvant treatment within 8-10 weeks after surgery Arm B FOLFOXIRI, part 1 (adjuvant) Oxaliplatin FOLFOX and FOLFOXIRI schedule FOLFOXIRI Irinotecan 165 mg/sqm iv over 60 minutes day 1, followed by Oxaliplatin 85 mg/sqm iv over 2 hours day 1, in two-way with L-Leucovorin 200 mg/sqm iv over 2 hours, day 1 followed by 5-fluoruracil 3200 mg/sqm 48 h-continuous infusion, starting on day 1; to be repeated every 2 weeks for a maximum of 12 cycles. In the case of oxaliplatin and/or irinotecan interruption because of adverse events, patient's refusal or investigator's choice, the continuation of the other drugs until 12 cycles is recommended. Arm A mFOLFOX6 or CAPOX (at investigator's choice), part 1 (adjuvant) 5-Fluorouracil continuous infusion FOLFOX schedule mFOLFOX6 Oxaliplatin 85 mg/sqm iv over 2 hours, day 1 in two-way with L-Leucovorin 200 mg/sqm iv over 2 hours, day 1 followed by 5-fluorouracil 400 mg/sqm iv bolus, day 1 followed by 5-fluoruracil 2400 mg/sqm 48 h-continuous infusion, starting on day 1; to be repeated every 2 weeks for a maximum of 12 cycles. The continuation of 5FU/leucovorin until 12 cycles is recommended also if oxaliplatin is interrupted because of adverse events, patient's refusal or investigator's choice. CAPOX Oxaliplatin 130 mg/sqm iv over 2 hours, day 1; Capecitabine 1000 mg/sqm/bid per os from day 1 to day 14; to be repeated every 3 weeks until 8 cycles. The continuation of Capecitabine until 8 cycles is recommended also if oxaliplatin is interrupted because of adverse events, patient's refusal or investigator's choice. Pending the results of ct-DNA analysis, up to 2 cycles of FOLFOX/CAPOX before randomization are allowed to start the adjuvant treatment within 8-10 weeks after surgery Trastuzumab and Tucatinib plus mFOLFOX6, part 1 target-driven (adjuvant) 5-Fluorouracil continuous infusion FOLFOX schedule Tucatinib 300 mg (two 150 mg tablets)/bid orally twice daily (approximately 8 to 12 hours between doses with or without a meal); Trastuzumab 4 mg/kg iv over 30 minutes, day 1 (loading dose: 6 mg/kg iv over 90 minutes), followed by mFOLFOX6 Oxaliplatin 85 mg/sqm iv over 2 hours, day 1 in two-way with L-Leucovorin 200 mg/sqm iv over 2 hours, day 1 followed by 5-fluorouracil 400 mg/sqm iv bolus, day 1 followed by 5-fluoruracil 2400 mg/sqm 48 h-continuous infusion, starting on day 1; to be repeated every 2 weeks for a maximum of 12 cycles. In the case of oxaliplatin and/or trastuzumab and/or tucatinib interruption because of adverse events, patient's refusal or investigator's choice, the prosecution of the other drugs until 12 cycles is recommended. Pending the results of ct-DNA analysis, up to 2 cycles of FOLFOX/CAPOX before randomization are allowed to start the adjuvant treatment within 8-10 weeks after surgery Arm B FOLFOXIRI, part 1 (adjuvant) 5-Fluorouracil continuous infusion FOLFOXIRI schedule FOLFOXIRI Irinotecan 165 mg/sqm iv over 60 minutes day 1, followed by Oxaliplatin 85 mg/sqm iv over 2 hours day 1, in two-way with L-Leucovorin 200 mg/sqm iv over 2 hours, day 1 followed by 5-fluoruracil 3200 mg/sqm 48 h-continuous infusion, starting on day 1; to be repeated every 2 weeks for a maximum of 12 cycles. In the case of oxaliplatin and/or irinotecan interruption because of adverse events, patient's refusal or investigator's choice, the continuation of the other drugs until 12 cycles is recommended. Arm A mFOLFOX6 or CAPOX (at investigator's choice), part 1 (adjuvant) 5-Fluorouracil bolus FOLFOX schedule mFOLFOX6 Oxaliplatin 85 mg/sqm iv over 2 hours, day 1 in two-way with L-Leucovorin 200 mg/sqm iv over 2 hours, day 1 followed by 5-fluorouracil 400 mg/sqm iv bolus, day 1 followed by 5-fluoruracil 2400 mg/sqm 48 h-continuous infusion, starting on day 1; to be repeated every 2 weeks for a maximum of 12 cycles. The continuation of 5FU/leucovorin until 12 cycles is recommended also if oxaliplatin is interrupted because of adverse events, patient's refusal or investigator's choice. CAPOX Oxaliplatin 130 mg/sqm iv over 2 hours, day 1; Capecitabine 1000 mg/sqm/bid per os from day 1 to day 14; to be repeated every 3 weeks until 8 cycles. The continuation of Capecitabine until 8 cycles is recommended also if oxaliplatin is interrupted because of adverse events, patient's refusal or investigator's choice. Pending the results of ct-DNA analysis, up to 2 cycles of FOLFOX/CAPOX before randomization are allowed to start the adjuvant treatment within 8-10 weeks after surgery Trastuzumab and Tucatinib plus mFOLFOX6, part 1 target-driven (adjuvant) 5-Fluorouracil bolus FOLFOX schedule Tucatinib 300 mg (two 150 mg tablets)/bid orally twice daily (approximately 8 to 12 hours between doses with or without a meal); Trastuzumab 4 mg/kg iv over 30 minutes, day 1 (loading dose: 6 mg/kg iv over 90 minutes), followed by mFOLFOX6 Oxaliplatin 85 mg/sqm iv over 2 hours, day 1 in two-way with L-Leucovorin 200 mg/sqm iv over 2 hours, day 1 followed by 5-fluorouracil 400 mg/sqm iv bolus, day 1 followed by 5-fluoruracil 2400 mg/sqm 48 h-continuous infusion, starting on day 1; to be repeated every 2 weeks for a maximum of 12 cycles. In the case of oxaliplatin and/or trastuzumab and/or tucatinib interruption because of adverse events, patient's refusal or investigator's choice, the prosecution of the other drugs until 12 cycles is recommended. Pending the results of ct-DNA analysis, up to 2 cycles of FOLFOX/CAPOX before randomization are allowed to start the adjuvant treatment within 8-10 weeks after surgery Arm A mFOLFOX6 or CAPOX (at investigator's choice), part 1 (adjuvant) Oxaliplatin FOLFOX and FOLFOXIRI schedule mFOLFOX6 Oxaliplatin 85 mg/sqm iv over 2 hours, day 1 in two-way with L-Leucovorin 200 mg/sqm iv over 2 hours, day 1 followed by 5-fluorouracil 400 mg/sqm iv bolus, day 1 followed by 5-fluoruracil 2400 mg/sqm 48 h-continuous infusion, starting on day 1; to be repeated every 2 weeks for a maximum of 12 cycles. The continuation of 5FU/leucovorin until 12 cycles is recommended also if oxaliplatin is interrupted because of adverse events, patient's refusal or investigator's choice. CAPOX Oxaliplatin 130 mg/sqm iv over 2 hours, day 1; Capecitabine 1000 mg/sqm/bid per os from day 1 to day 14; to be repeated every 3 weeks until 8 cycles. The continuation of Capecitabine until 8 cycles is recommended also if oxaliplatin is interrupted because of adverse events, patient's refusal or investigator's choice. Pending the results of ct-DNA analysis, up to 2 cycles of FOLFOX/CAPOX before randomization are allowed to start the adjuvant treatment within 8-10 weeks after surgery Arm A mFOLFOX6 or CAPOX (at investigator's choice), part 1 (adjuvant) Oxaliplatin CAPOX schedule mFOLFOX6 Oxaliplatin 85 mg/sqm iv over 2 hours, day 1 in two-way with L-Leucovorin 200 mg/sqm iv over 2 hours, day 1 followed by 5-fluorouracil 400 mg/sqm iv bolus, day 1 followed by 5-fluoruracil 2400 mg/sqm 48 h-continuous infusion, starting on day 1; to be repeated every 2 weeks for a maximum of 12 cycles. The continuation of 5FU/leucovorin until 12 cycles is recommended also if oxaliplatin is interrupted because of adverse events, patient's refusal or investigator's choice. CAPOX Oxaliplatin 130 mg/sqm iv over 2 hours, day 1; Capecitabine 1000 mg/sqm/bid per os from day 1 to day 14; to be repeated every 3 weeks until 8 cycles. The continuation of Capecitabine until 8 cycles is recommended also if oxaliplatin is interrupted because of adverse events, patient's refusal or investigator's choice. Pending the results of ct-DNA analysis, up to 2 cycles of FOLFOX/CAPOX before randomization are allowed to start the adjuvant treatment within 8-10 weeks after surgery Trastuzumab and Tucatinib plus mFOLFOX6, part 1 target-driven (adjuvant) Oxaliplatin FOLFOX and FOLFOXIRI schedule Tucatinib 300 mg (two 150 mg tablets)/bid orally twice daily (approximately 8 to 12 hours between doses with or without a meal); Trastuzumab 4 mg/kg iv over 30 minutes, day 1 (loading dose: 6 mg/kg iv over 90 minutes), followed by mFOLFOX6 Oxaliplatin 85 mg/sqm iv over 2 hours, day 1 in two-way with L-Leucovorin 200 mg/sqm iv over 2 hours, day 1 followed by 5-fluorouracil 400 mg/sqm iv bolus, day 1 followed by 5-fluoruracil 2400 mg/sqm 48 h-continuous infusion, starting on day 1; to be repeated every 2 weeks for a maximum of 12 cycles. In the case of oxaliplatin and/or trastuzumab and/or tucatinib interruption because of adverse events, patient's refusal or investigator's choice, the prosecution of the other drugs until 12 cycles is recommended. Pending the results of ct-DNA analysis, up to 2 cycles of FOLFOX/CAPOX before randomization are allowed to start the adjuvant treatment within 8-10 weeks after surgery Trastuzumab and Tucatinib plus mFOLFOX6, part 1 target-driven (adjuvant) Oxaliplatin CAPOX schedule Tucatinib 300 mg (two 150 mg tablets)/bid orally twice daily (approximately 8 to 12 hours between doses with or without a meal); Trastuzumab 4 mg/kg iv over 30 minutes, day 1 (loading dose: 6 mg/kg iv over 90 minutes), followed by mFOLFOX6 Oxaliplatin 85 mg/sqm iv over 2 hours, day 1 in two-way with L-Leucovorin 200 mg/sqm iv over 2 hours, day 1 followed by 5-fluorouracil 400 mg/sqm iv bolus, day 1 followed by 5-fluoruracil 2400 mg/sqm 48 h-continuous infusion, starting on day 1; to be repeated every 2 weeks for a maximum of 12 cycles. In the case of oxaliplatin and/or trastuzumab and/or tucatinib interruption because of adverse events, patient's refusal or investigator's choice, the prosecution of the other drugs until 12 cycles is recommended. Pending the results of ct-DNA analysis, up to 2 cycles of FOLFOX/CAPOX before randomization are allowed to start the adjuvant treatment within 8-10 weeks after surgery Arm B Trifluridine/Tipiracil, part 2 (post-adjuvant) Trifluridine/Tipiracil Trifluridine/Tipiracil: 35 mg/ m2/bid per os days 1-5 and 8-12 to be repeated every 4 weeks until 6 cycles. Arm B FOLFOXIRI, part 1 (adjuvant) Irinotecan FOLFOXIRI Irinotecan 165 mg/sqm iv over 60 minutes day 1, followed by Oxaliplatin 85 mg/sqm iv over 2 hours day 1, in two-way with L-Leucovorin 200 mg/sqm iv over 2 hours, day 1 followed by 5-fluoruracil 3200 mg/sqm 48 h-continuous infusion, starting on day 1; to be repeated every 2 weeks for a maximum of 12 cycles. In the case of oxaliplatin and/or irinotecan interruption because of adverse events, patient's refusal or investigator's choice, the continuation of the other drugs until 12 cycles is recommended. Arm A mFOLFOX6 or CAPOX (at investigator's choice), part 1 (adjuvant) Capecitabine mFOLFOX6 Oxaliplatin 85 mg/sqm iv over 2 hours, day 1 in two-way with L-Leucovorin 200 mg/sqm iv over 2 hours, day 1 followed by 5-fluorouracil 400 mg/sqm iv bolus, day 1 followed by 5-fluoruracil 2400 mg/sqm 48 h-continuous infusion, starting on day 1; to be repeated every 2 weeks for a maximum of 12 cycles. The continuation of 5FU/leucovorin until 12 cycles is recommended also if oxaliplatin is interrupted because of adverse events, patient's refusal or investigator's choice. CAPOX Oxaliplatin 130 mg/sqm iv over 2 hours, day 1; Capecitabine 1000 mg/sqm/bid per os from day 1 to day 14; to be repeated every 3 weeks until 8 cycles. The continuation of Capecitabine until 8 cycles is recommended also if oxaliplatin is interrupted because of adverse events, patient's refusal or investigator's choice. Pending the results of ct-DNA analysis, up to 2 cycles of FOLFOX/CAPOX before randomization are allowed to start the adjuvant treatment within 8-10 weeks after surgery Trastuzumab and Tucatinib plus mFOLFOX6, part 1 target-driven (adjuvant) Trastuzumab Tucatinib 300 mg (two 150 mg tablets)/bid orally twice daily (approximately 8 to 12 hours between doses with or without a meal); Trastuzumab 4 mg/kg iv over 30 minutes, day 1 (loading dose: 6 mg/kg iv over 90 minutes), followed by mFOLFOX6 Oxaliplatin 85 mg/sqm iv over 2 hours, day 1 in two-way with L-Leucovorin 200 mg/sqm iv over 2 hours, day 1 followed by 5-fluorouracil 400 mg/sqm iv bolus, day 1 followed by 5-fluoruracil 2400 mg/sqm 48 h-continuous infusion, starting on day 1; to be repeated every 2 weeks for a maximum of 12 cycles. In the case of oxaliplatin and/or trastuzumab and/or tucatinib interruption because of adverse events, patient's refusal or investigator's choice, the prosecution of the other drugs until 12 cycles is recommended. Pending the results of ct-DNA analysis, up to 2 cycles of FOLFOX/CAPOX before randomization are allowed to start the adjuvant treatment within 8-10 weeks after surgery Trastuzumab and Tucatinib plus mFOLFOX6, part 1 target-driven (adjuvant) Tucatinib Tucatinib 300 mg (two 150 mg tablets)/bid orally twice daily (approximately 8 to 12 hours between doses with or without a meal); Trastuzumab 4 mg/kg iv over 30 minutes, day 1 (loading dose: 6 mg/kg iv over 90 minutes), followed by mFOLFOX6 Oxaliplatin 85 mg/sqm iv over 2 hours, day 1 in two-way with L-Leucovorin 200 mg/sqm iv over 2 hours, day 1 followed by 5-fluorouracil 400 mg/sqm iv bolus, day 1 followed by 5-fluoruracil 2400 mg/sqm 48 h-continuous infusion, starting on day 1; to be repeated every 2 weeks for a maximum of 12 cycles. In the case of oxaliplatin and/or trastuzumab and/or tucatinib interruption because of adverse events, patient's refusal or investigator's choice, the prosecution of the other drugs until 12 cycles is recommended. Pending the results of ct-DNA analysis, up to 2 cycles of FOLFOX/CAPOX before randomization are allowed to start the adjuvant treatment within 8-10 weeks after surgery
- Primary Outcome Measures
Name Time Method ct-DNA clearance rate after the end of the adjuvant treatment (ERASE-CRC part 1) 6 months from the enrollment of the last patient in the adjuvant treatment Percentage of patients, relative to the total of enrolled subjects in the Part 1 of the study with undetectable ct-DNA at the end of adjuvant treatment.
ct-DNA clearance rate after the end of post-adjuvant treatment (ERASE-CRC part 2) 6 months from the enrollment of the last patient in post-adjuvant treatment Percentage of patients, relative to the total of enrolled subjects in the Part 2 of the study with undetectable ct-DNA at the end of post-adjuvant treatment.
ct-DNA clearance rate after the end of target-driven adjuvant treatment (ERASE-CRC part 1 target-driven) 6 months from the enrollment of the last patient in the target-driven adjuvant treatment Percentage of patients, relative to the total of enrolled subjects in the target-driven part
1 of the study with undetectable ct-DNA at the end of adjuvant treatment.
- Secondary Outcome Measures
Name Time Method Overall Toxicity Rate 1 30 days from the last dose of the last patient in adjuvant treatment Percentage of patients, relative to the total of enrolled subjects in the Part 1 of the study, experiencing any adverse event, according to National Cancer Institute Common Toxicity Criteria (version 5.0), during adjuvant treatment and follow-up.
Disease Free Survival 1 (DFS1) 60 months after the randomization of first patient in adjuvant treatment Time from randomization of the part 1 of the study to the first documentation of radiological disease relapse or death due to any cause, whichever occurs first. Secondary colorectal cancers are regarded as DFS events, whereas non-colorectal tumors are not. DFS will be censored on the date of the last evaluable on study tumor assessment documenting absence of relapse for patients who are alive, on study and disease free at the time of the analysis. Alive patients having no tumor assessments after randomization will have time to event censored on the date of randomization.
Disease Free Survival 2 (DFS2) 60 months after the randomization of first patient in post-adjuvant treatment Time from randomization of the part 2 of the study to the first radiological documentation of disease relapse or death due to any cause, whichever occurs first. Secondary colorectal cancers are regarded as DFS events, whereas non-colorectal tumors are not. DFS will be censored on the date of the last evaluable on study tumor assessment documenting absence of relapse for patients who are alive, on study and disease free at the time of the analysis. Alive patients having no tumor assessments after randomization will have time to event censored on the date of randomization.
Overall Survival 2 (OS2) 60 months after the randomization of first patient in post-adjuvant treatment Time from randomization of the part 2 of the study to the date of death due to any cause. For patients still alive at the time of analysis, the OS time will be censored on the last date the patients were known to be alive.
Toxicity Rate TD1 30 days from the last dose of the last patient in target-driven adjuvant treatment percentage of patients, relative to the total of enrolled subjects in the target-driven part 1 of the study, experiencing a specific adverse event ≥ grade 3, according to National Cancer Institute Common Toxicity Criteria (version 5.0), during adjuvant treatment and follow-up.
Toxicity Rate 1 30 days from the last dose of the last patient in adjuvant treatment Percentage of patients, relative to the total of enrolled subjects in the Part 1 of the study, experiencing a specific adverse event of grade ≥ 3, according to National Cancer Institute Common Toxicity Criteria (version 5.0), during adjuvant treatment and follow-up.
Overall Survival 1 (OS1) 60 months after the randomization of first patient in adjuvant treatment Time from randomization of the Part 1 of the study to the date of death due to any cause. For patients still alive at the time of the analysis, the OS time will be censored on the last date the patients were known to be alive.
Overall Toxicity Rate 2 30 days from the last dose of TRIFLURIDINE/TIPIRACIL Percentage of patients in the Part 2 of the study, relative to the total of enrolled subjects, experiencing any adverse event, according to National Cancer Institute Common Toxicity Criteria (version 5.0), during post-adjuvant treatment and follow-up.
Toxicity Rate 2 30 days from the last dose of TRIFLURIDINE/TIPIRACIL Percentage of patients, relative to the total of enrolled subjects in the Part 2 of the study, experiencing a specific adverse event of grade 3/4, according to National Cancer Institute Common Toxicity Criteria (version 5.0), during postadjuvant treatment and follow-up.
Disease Free Survival TD1 (DFS-TD1) 60 months after the randomization of first patient in adjuvant treatment time from enrollment of the target-driven part 1 of the study to the first documentation of disease relapse or death due to any cause, whichever occurs first. Secondary colorectal cancers are regarded as DFS events, whereas non-colorectal tumors are not. DFS will be censored on the date of the last evaluable on study tumor assessment documenting absence of relapse for patients who are alive, on study and disease free at the time of the analysis. Alive patients having no tumor assessments after enrollment will have time to event censored on the date of enrollment.
Overall survival TD1 (OS-TD1) 60 months after the randomization of first patient in adjuvant treatment Time from enrollment of the target-driven part 1 of the study to the date of death due to any cause. For patients still alive at the time of the analysis, the OS time will be censored on the last date the patients were known to be alive.
Overall Toxicity Rate TD1 30 days from the last dose of the last patient in target-driven adjuvant treatment Percentage of patients, relative to the total of enrolled subjects in the target-driven part 1 of the study, experiencing any adverse event, according to National Cancer Institute Common Toxicity Criteria (version 5.0), during adjuvant treatment and follow-up.
Trial Locations
- Locations (28)
Fondazione Casa Sollievo della Sofferenza
🇮🇹San Giovanni Rotondo, Foggia, Italy
Azienda Ospedaliera Cardinale Giovanni Panico
🇮🇹Tricase, Lecce, Italy
Ospedale San Donato di Arezzo
🇮🇹Arezzo, Italy
Azienda Sanitaria Universitaria Friuli Centrale
🇮🇹Udine, Italy
Spedali Civili di Brescia
🇮🇹Brescia, Italy
AOU Cagliari PO Policlinico Universitario Duilio Casula Presidio Policlinico Universitario "Duilio Casula"
🇮🇹Cagliari, Italy
A.O.U Careggi
🇮🇹Firenze, Italy
E.O. Ospedali Galliera di Genova
🇮🇹Genova, Italy
Fondazione POLIAMBULANZA ISTITUTO OSPEDALIERO
🇮🇹Brescia, Italy
A.O.U. di Ferrara Arcispedale Sant'Anna
🇮🇹Ferrara, Italy
Ospedale Misericordia di Grosseto
🇮🇹Grosseto, Italy
Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori"
🇮🇹Meldola, Italy
Azienda USL Toscana Nord Ovest di Livorno
🇮🇹Livorno, Italy
Ospedale San Luca di Lucca
🇮🇹Lucca, Italy
Istituto Oncologico Veneto IOV - IRCCS
🇮🇹Padua, Italy
Ospedale San Raffaele
🇮🇹Milano, Italy
Azienda Ospedaliero Universitaria Maggiore della Carita
🇮🇹Novara, Italy
Fondazione IRCCS INT - Milano
🇮🇹Milan, Italy
Azienda USL di Piacenza
🇮🇹Piacenza, Italy
Nuovo Ospedale di Prato
🇮🇹Prato, Italy
AUSL Romagna
🇮🇹Ravenna, Italy
Istituto per la ricerca sui tumori Regina Elena
🇮🇹Roma, Italy
Azienda USL IRCCS di Reggio Emilia (centro principale Reggio Emilia e centro satellite Guastalla).
🇮🇹Reggio Emilia, Italy
Policlinico Fondazione Agostino Gemelli
🇮🇹Roma, Italy
Ospedale Fatebenefratelli Isola Tiberina
🇮🇹Roma, Italy
Policlinico Tor Vergata Roma
🇮🇹Roma, Italy
IRCCS di Candiolo
🇮🇹Torino, Italy
Ospedale Campostaggia Poggiponsi
🇮🇹Siena, Italy