STAGE III AND HIGH-RISK STAGE II RESECTED COLON CANCER PATIENTS. MedDRA version: 21.0 Level: PT Classification code 10009955 Term: Colon cancer stage III System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.0 Level: PT Classification code 10009954 Term: Colon cancer stage II System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Calcio Levofolinato
Product Code: [Calcio Levofolinato]
Pharmaceutical Form: Powder for solution for injection/infusion
INN or Proposed INN: CALCIO LEVOFOLINATO
CAS Number: 80433-71-2
Cu
Sponsors
Fondazione GONO
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Part 1: 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; 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); Women of childbearing potential must have a negative blood pregnancy test at the screening visit. Part 2: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 PS = 1; Women of childbearing potential must have a negative blood pregnancy test at the screening visit. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 259 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 200
Exclusion criteria
Exclusion criteria: Part 1 and Part 2 Any evidence of metastatic disease (radiological or pathological metastasis); Macroscopic or microscopic evidence of residual tumor (R1 or R2 resections) after surgery; 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; Lack of physical integrity of the upper gastrointestinal tract, malabsorption syndrome, or inability to take oral medication; Pregnant or lactating women
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: PART 1 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. PART 2 to assess the rate of ct-DNA clearance at the end of post-adjuvant treatment with trifluridine/tipiracil for 6 cycles 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.;Secondary Objective: PART 1 to assess: Safety profiles of study treatments, duration of DFS; duration of OS, prognostic impact of the post-surgery detection of ct-DNA, prognostic impact of the clearance of ct-DNA at the end of the adj therapy, ct-DNA clearance during the adjuvant treatment as a surrogate marker of the efficacy of the adj therapy, quality of life by PROs questionnaires will be assessed and compared between the treatment arms, translational analyses. PART 2 to assess: Safety profile; duration of DFS, duration of OS, prognostic impact of the post-adj detection of ct-DNA, prognostic impact of the clearance of ct-DNA at the end of the post-adj therapy, ct-DNA clearance during the post-adj treatment as a surrogate marker of efficacy, quality of life by PROs questionnaires will be assessed and compared between the treatment arms, translational analyses.;Primary end point(s): Part 1: ct-DNA clearance rate after the end of the adjuvant treatment is defined as the 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. Part 2: ct-DNA clearance rate after the end of post-adjuvant treatment is defined as the 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.;Timepoint(s) of evaluation of this end point: Part 1 within 6 months from the adjuvant | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Part 1 and Part 2 The analysis of PROs endpoints (assessed using the EORTC QLQ-C30, the EORTC QLQCR29 and the EuroQol EQ-5D questionnaires) will be assessed according to the EORTC Scoring and Reference Values Manual. All scores and subscales will be compared between the treatment arms.; PART 1 - Overall Toxicity Rate 1 is defined as the 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. - Toxicity Rate 1 is defined as the percentage of patients, relative to the total of enrolled subjects in the 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. PART 2 - Overall Toxicity Rate 2 is defined as the 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 is defined as the 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, according to National Cancer Institute Common Toxicity Criteria (version 5.0), during post-adjuvant treatment and follow-up.; Part 1: Disease Free Survival 1 is defined as the 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. Part 2: Disease Free Survival 2 is defined as the 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.; PART 1 Overall survival 1 is defined as the time from | — |
Countries
Italy
Contacts
Public ContactUfficio Sperimentazioni sede operat
Fondazione GONO
Outcome results
None listed