There is one clinical trial.
Patients with metastatic colorectal cancer (mCRC) who have received all approved standard treatments (except Regorafenib and TAS 102) no longer have treatment options available while maintaining a good performance status which would allow them to receive a new treatment
Inclusion Criteria: - Signed informed consent obtained before any study specific procedures - Male or female ≥ 18 years of age - Histological or cytological documentation of adenocarcinoma of the colon or rectum - Patients with metastatic colorectal cancer - Progression during or within 3 months following the last administration of approved standard therapies, which must include a fluoropyrimidine (or raltitrexed), oxaliplatin, irinotecan, anti VEGF therapy and an anti EGFR therapy (for RAS wild-type tumors) - ECOG performance status ≤1 - Life expectancy of at least 3 months - Patients with A/A CCND1 genotype of rs603965 CCND1 - Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements conducted within 7 days of starting study treatment: Amylase and lipase ≤1.5 x ULN,Total bilirubin ≤ 1.5 x ULN,Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3.0 x ULN (≤ 5 x ULN for patients with liver involvement of their cancer), Alkaline phosphatase (ALP) ≤ 2.5 x ULN (≤ 5.0 x ULN for patients with liver involvement for their cancer and/or have bone metastases), Platelet count ≥ 100,000/mm3; Hemoglobin (Hb) ≥ 9 g/dL; Absolute neutrophil count (ANC) ≥ 1,500/ mm3.
Exclusion Criteria: - Patients with A/G or G/G CCND1 genotype of rs603965 CCND1 - Prior treatment with regorafenib or sorafenib - Prior treatment with TAS 102 - Major surgical procedure, open biopsy, or significant traumatic injury within 28 days before start of study drug - Pregnant or breast-feeding subjects.
(Systolic blood pressure > 140 mmHg or diastolic pressure > 90 mmHg despite optimal medical management) - Pleural effusion or ascites that causes respiratory compromise (≥ NCI-CTCAE V5.0 Grade 2 dyspnea) - Ongoing infection > Grade 2 NCI-CTCAE V5.0 - Known history of human immunodeficiency virus (HIV) infection - Active hepatitis B or C, or chronic hepatitis B or C requiring treatment with antiviral therapy - Patients with seizure disorder requiring medication - History of organ allograft - Patients with evidence or history of any bleeding diathesis, irrespective of severity - Any hemorrhage or bleeding event ≥ NCI-CTC V5.0 Grade 3 within 4 weeks prior to the start of study medication - Non-healing wound, ulcer, or bone fracture - Dehydration NCI-CTCAE V5.0 Grade ≥ 1 - Substance abuse, medical, psychological or social conditions that may interfere with the subject's participation in the study or evaluation of the study results - Known hypersensitivity to any of the study drugs, study drug classes, or excipients in the formulation - Any illness or medical conditions that are unstable or could - jeopardize the safety of the subject and his/her compliance in the study - Persistent proteinuria of NCI-CTCAE V5.0 Grade 3 (> 3.5g/24 hours) - Patients unable to swallow oral medications - Any malabsorption condition - Chronic inflammatory bowel disease and / or bowel obstruction - Unresolved toxicity higher than NCI-CTCAE V.5.0 Grade 1 attributed to any prior therapy/procedure excluding alopecia, hypothyroidism and oxaliplatin induced neurotoxicity ≤ Grade 2 - Concomitant participation or participation within the last 30 days in another clinical trial - Systemic anticancer therapy during this trial or within 4 weeks before randomization - Concomitant intake of st John's wort - Live attenuated vaccines are prohibited 10 days before the treatment, during the treatment and 6 months after the termination of treatment - History of gastrointestinal fistula or perforation Inclusion Criteria: - Signed informed consent obtained before any study specific procedures - Male or female ≥ 18 years of age - Histological or cytological documentation of adenocarcinoma of the colon or rectum - Patients with metastatic colorectal cancer - Progression during or within 3 months following the last administration of approved standard therapies, which must include a fluoropyrimidine (or raltitrexed), oxaliplatin, irinotecan, anti VEGF therapy and an anti EGFR therapy (for RAS wild-type tumors) - ECOG performance status ≤1 - Life expectancy of at least 3 months - Patients with A/A CCND1 genotype of rs603965 CCND1 - Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements conducted within 7 days of starting study treatment: Amylase and lipase ≤1.5 x ULN,Total bilirubin ≤ 1.5 x ULN,Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3.0 x ULN (≤ 5 x ULN for patients with liver involvement of their cancer), Alkaline phosphatase (ALP) ≤ 2.5 x ULN (≤ 5.0 x ULN for patients with liver involvement for their cancer and/or have bone metastases), Platelet count ≥ 100,000/mm3; Hemoglobin (Hb) ≥ 9 g/dL; Absolute neutrophil count (ANC) ≥ 1,500/ mm3.
The A870A rs603965 polymorphism of cyclin D1, a molecule involved in the initiation of cell division, was favorable to the NEXIRI combination on overall survival with a median of 19.6 months versus 6.2 months for two other genotypes A/G and G/G.
Description: From randomization of first patient until the datebase cut-off
Measure: Overall survival Time: Approximately 36 monthsDescription: From randomization of first patient until the datebase cut-off,
Measure: Progression-free survival (PFS) Time: Approximately 36 monthsDescription: From randomization of first patient until the datebase cut-off,
Measure: Disease control rate (DCR) Time: Tumor is assessed every 8 weeksDescription: From randomization of first patient until the datebase cut-off,
Measure: Objective response rate (OOR) Time: Tumor is assessed at 8 weeks intervalsDescription: From randomization of first patient until the end of treatment,
Measure: Assessment of adverse events by using the NCI-CTCAE version 5.0 scale Time: Approximately 36 monthsDescription: From date of randomization until the date of end of treatment
Measure: Quality of life questionnaire Time: questionnaire is assessed at 8 weeks intervals