SNPMiner Trials (Home Page)
Report for Clinical Trial NCT03829462
Developed by Shray Alag, 2020.
SNP Clinical Trial Gene
A Randomized Phase III Trial Assessing a Regorafenib-irinotecan Combination (REGIRI) Versus Regorafenib Alone in Metastatic Colorectal Cancer Patients After Failure of Standard Therapies, According to the A/A Genotype of Cyclin D1
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
NCT03829462 Metastatic Colorectal Cancer (mCRC) MeSH:Colorectal Neoplasms
HPO:Neoplasm of the large intestine
2 Interventions
Name: Regorafenib
Name: Irinotecan
Primary Outcomes
Description: From randomization of first patient until the datebase cut-off
Measure: Overall survival Time: Approximately 36 monthsSecondary Outcomes
Description: 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 intervalsPurpose: Treatment
Allocation: Randomized
Parallel Assignment
There is one SNP
SNPs
1 rs603965
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.