Genetic Polymorphism oriented Phase II Study of Irinotecan and Doxifluridine for Unresectable or Recurrent Colorectal Cancer
Ontology highlight
ABSTRACT:
DISEASE(S): Colorectal Cancer
PROVIDER: 2620453 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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Project description:A phase I trial of a SRC kinase Inhibitor, dasatinib, in combination with paclitaxel and carboplatin in patients with advanced or recurrent ovarian cancer. Background: We conducted a phase I study of dasatinib, an oral SRC tyrosine kinase inhibitor, in combination with paclitaxel and carboplatin in advanced and recurrent epithelial ovarian cancer (EOC). Methods: The primary objective was to determine the maximum tolerated dose (MTD). Secondary objectives included toxicity, response rate (RR), pharmacokinetics and pharmacodynamics. Based on the 3+3 design, cohorts of 3-6 pts received paclitaxel 175 mg/m2 and carboplatin AUC 6 every three weeks with escalating doses of dasatinib (100, 120, 150 mg daily), followed by an 8 patient expansion cohort. Results: Twenty patients were enrolled between 06/07 and 12/09. The median age was 61 yrs (42-82) with a median of 2 prior regimens (0-6), and 71% had platinum-sensitive disease. There were 3-6 pts in each cohort, and 8 in the expansion cohort. Pharmacokinetics were observed over the first 2 cycles of therapy. One DLT was observed in the 100 mg dasatinib cohort (grade 3 myalgia. Other toxicities in all cycles included neutropenia (95% grade 3-4), thrombocytopenia (35% grade 3-4), and fatigue (10% grade 3). The RR was 45% (complete responses, 3/18(17%); partial responses, 5/18(28%)) and 56% (10/18) had stable disease. The PFS6-month actuarial estimate was 86%. The median PFS and OS were 7.8 and 16.2 months, respectively. Conclusions: Due to the high incidence of myelosuppression with subsequent cycles the recommended phase II dose is 150 mg daily of dasatinib in combination with paclitaxel and carboplatin. The combination was safe with evidence of clinical activity in advanced EOC.
2012-04-12 | GSE37180 | GEO
Project description:A phase I trial of a SRC kinase Inhibitor, dasatinib, in combination with paclitaxel and carboplatin in patients with advanced or recurrent ovarian cancer. Background: We conducted a phase I study of dasatinib, an oral SRC tyrosine kinase inhibitor, in combination with paclitaxel and carboplatin in advanced and recurrent epithelial ovarian cancer (EOC). Methods: The primary objective was to determine the maximum tolerated dose (MTD). Secondary objectives included toxicity, response rate (RR), pharmacokinetics and pharmacodynamics. Based on the 3+3 design, cohorts of 3-6 pts received paclitaxel 175 mg/m2 and carboplatin AUC 6 every three weeks with escalating doses of dasatinib (100, 120, 150 mg daily), followed by an 8 patient expansion cohort. Results: Twenty patients were enrolled between 06/07 and 12/09. The median age was 61 yrs (42-82) with a median of 2 prior regimens (0-6), and 71% had platinum-sensitive disease. There were 3-6 pts in each cohort, and 8 in the expansion cohort. Pharmacokinetics were observed over the first 2 cycles of therapy. One DLT was observed in the 100 mg dasatinib cohort (grade 3 myalgia. Other toxicities in all cycles included neutropenia (95% grade 3-4), thrombocytopenia (35% grade 3-4), and fatigue (10% grade 3). The RR was 45% (complete responses, 3/18(17%); partial responses, 5/18(28%)) and 56% (10/18) had stable disease. The PFS6-month actuarial estimate was 86%. The median PFS and OS were 7.8 and 16.2 months, respectively. Conclusions: Due to the high incidence of myelosuppression with subsequent cycles the recommended phase II dose is 150 mg daily of dasatinib in combination with paclitaxel and carboplatin. The combination was safe with evidence of clinical activity in advanced EOC. Global profiles of expression were characterized using unsupervised clustering methods and gene- and pathway-analyses of differential expression.
2012-04-11 | E-GEOD-37180 | biostudies-arrayexpress
Project description:Interventions: FOLFIRI plus ziv-aflibercept
(Day 1) Ziv-aflibercept, 4 mg/kg, intravenously (IV) over 60 min
(Day 1) Irinotecan, 150 mg/m2, IV over 90 min
(Day 1) Leucovorin (l-LV), 200 mg/m2, IV over 120 min
(Day 1) 5-FU, 400 mg/m2, bolus
(Day 1-3) 5-FU, 2400 mg/m2, continuous infusion over 46 h
Repeat the above every two weeks
The dose of irinotecan can be reduced to 120 mg/m2 if patients are homozygous for UGT1A1*28 or UGT1A1*6, or heterozygous for both UGT1A1*28 and UGT1A1*6.;C480833,C533178;FOLFIRI, ziv-aflibercept
Primary outcome(s): progression free survival
Study Design: single arm study, open(masking not used), historical control, single assignment, treatment purpose
| 2614963 | ecrin-mdr-crc
Project description:Intervention name : TAS-102
Dosage And administration of the intervention : TAS-102 as a starting dose of 25 mg/m2/dose BID (50 mg/m2/day) is administered orally in a 28-day cycle (2-week cycle of 5 days of treatment followed by a 2-day rest period, and then a 14-day rest period).
Control intervention name : irinotecan
INN of the control intervention : irinotecan
Dosage And administration of the control intervention : Irinotecan is administered by intravenous infusion at a dose of 150 mg/m2 over 90 minutes on day 1 and 15.
Primary outcome(s): Safety
CTCAE (ver.3.0)
Study Design: Open-label, multi-center, phase I study
| 2610898 | ecrin-mdr-crc
Project description:Interventions: Cetuximab 500 mg/M2/2week Irinotecan 150 mg/M2/2week
Primary outcome(s): Response rate
Study Design: Single arm Non-randomized
| 2635175 | ecrin-mdr-crc
Project description:Interventions: Step1: Confirmation of dosage of each drug (Oxaliplatin and Irinotecan)
i)Induction treatment
The following drugs will be administered in 3week/cycle for 6cycles (maximum 8cycle, if investigator required). With regard to determination of oxaliplatin (OX) and Irinotecan (IRI) dosage, initial 3patients (pts) will be enrolled of level0. After finishing initial enrollment, Steering committee (SC) will evaluate safety of 3pts at the time of starting of cycle2 and will decide whether the proceeding same level (add 3 pts) or other level (level+1 or level-0.5). Final decision of Recommended Dose (RD) of OX and IRI will be required 6pts of safety evaluation in same level and will be endorsed by SC and Independent Data monitoring committee (IDMC).
1) Each drug dosage of CAPOXIRI+Bevacizumab
Bevacizumab (BEV: 7.5 mg/kg, i.v., 90, 60, 30 min, Day 1)
Irinotecan (IRI: 130 mg/m2, i.v., 90 min, Day 1)
Oxaliplatin (OX: 200 mg/m2, i.v., 120 min, Day 1)
Capecitabine (CAP: 800 mg/m2 p.o., twice daily, 14 days consecutively)
2) OX and IRI dose level
Level +1: IRI: 200 mg/m2, OX:130mg/m2
Level 0: IRI: 200 mg/m2, OX:100mg/m2
Level -0.5: IRI: 180 mg/m2, OX:100mg/m2
Level -1: IRI: 150 mg/m2, OX:100mg/m2
ii)Maintenance treatment
After finishing the induction treatment, investigator will select 1) 5-FU/LV+BEV (2weeks cycle) or 2) CAP+BEV treatment (3weeks/cycle).
1)5-FU/LV+BEV treatment
The following drugs will be administered in 2week/cycle until meeting discontinuation criteria.
- Each drug dosage of 5-FU/LV+BEV -
Bevacizumab (BEV: 5.0 mg/kg, i.v., 90, 60, 30 min, Day 1)
Leucovorin (LV: 200 mg/m2, i.v., 120 min, Day 1)
5-FU (3200 mg/m2, c.i.v., 48 hours, Day 1-3)
2)CAP+BEV treatment
The following drugs will be administered in 2week/cycle until meeting discontinuation criteria.
- Each
Primary outcome(s): Progression-free survival (PFS)
Study Design: randomized controlled trial, open(masking not used), active control, parallel assignment, treatment purpose
| 2614949 | ecrin-mdr-crc
Project description:Interventions: FOLFIRI + bevacizumab consisted of bevacizumab 5mg/kg as a 90-minute infusion, then, l-LV 200 mg/m2 as a 2-hour infusion, and irinotecan 150 mg/m2 given as a 90-minute infusion, followed by bolus FU 400 mg/m2 and a 46-hour infusion FU 2,400 mg/m2, repeated every 2 weeks.
IRIS + bevacizumab consisted of bevacizumab 7.5mg/kg as a 90-minute infusion, then, irinotecan 150 mg/m2 given as a 90-minute infusion, followed by oral S-1 (40 mg/m2) twice daily 14 days (day 3 to 16) followed by 5 days rest, repeated every 3 weeks.
Primary outcome(s): safety
Study Design: Parallel Randomized
| 2616274 | ecrin-mdr-crc
Project description:Interventions: FOLFOX 4 Treatment Day 1: 1. L-OHP 85mg/m2 is mixed with 250 cc of 5% glucose infusion.(A) 2. l-LV 100 mg/m2 is mixed with 250 cc of 5% glucose infusion.(B) 3. A and B are drip-infused by 2 hours using Y connection. 4. 5-FU 400mg/m2 is infused by 15 minutes, intravenously 5. 5-FU 600 mg/m2 is infused by 22 hours. Day 2: 1. l-LV 100mg/m2 is infused by 2 hours. 2. 5-FU 400 mg/m2 is infused by 15 minutes. 3. 5-FU 600 mg/m2 is infused by 22 hours
Primary outcome(s): Response Rate
Study Design: Single arm Non-randomized
| 2616238 | ecrin-mdr-crc
Project description:Interventions: investigational material(s)
Generic name etc : TAS-102
INN of investigational material :
Therapeutic category code : 422 Antimetabolic agents
Dosage and Administration for Investigational material : TAS-102 as a starting dose of 25 mg/m2/dose BID (50 mg/m2/day) is administered orally in a 28-day cycle (2-week cycle of 5 days of treatment followed by a 2-day rest period, and then a 14-day rest period).
control material(s)
Generic name etc : irinotecan
INN of investigational material : irinotecan
Therapeutic category code : 424 Antineoplastic preparations extracted from plants
Dosage and Administration for Investigational material : Irinotecan is administered by intravenous infusion at a dose of 150 mg/m2 over 90 minutes on day 1 and 15.
Primary outcome(s): Safety
CTCAE (ver.3.0)
Study Design: Open-label, multi-center, phase I study
| 100929 | ecrin-mdr-crc
Project description:Polyamines, including putrescine (PUT), spermidine (SPD) and spermine (SPM), are abundant polycations supporting various cellular functions. Their cellular content is tightly controlled by biosynthesis, degradation and uptake or export via the polyamine transport system (PTS). However, the mammalian PTS remains poorly characterized. Mutated Chinese hamster ovary cells, CHO-MG, are frequently used to study the PTS owing to their phenotype of reduced polyamine uptake and resistance to methylglyoxal bis-(guanylhydrazone) (MGBG), a toxic polyamine biosynthesis inhibitor. Yet, the underlying genetic defect remains enigmatic. We recently proved that the P5B-type ATPase, ATP13A2, is a polyamine transporter and here, we analyzed whether the P5B-type ATPases are deficient in CHO-MG. Label-free shogun proteomics found that ATP13A3 expression is reduced in CHO-MG. Mutations in the ATP13A3 gene were found to critically disturb the protein sequence. Interestingly, depleting ATP13A3 in the wild-type CHO cells induced a CHO-MG phenotype, whereas its complementation in CHO-MG rescued the phenotype. Together, we demonstrate that defective ATP13A3 contributes to the CHO-MG phenotype, designating ATP13A3 as a new member of the mammalian PTS that may partially overlap in function with ATP13A2.
2020-12-09 | PXD020559 | Pride