Dataset Information

To study the effect of two drugs Capecitabine 500 mg (Test product by Reliance Life Sciences Pvt. Ltd., India) and XelodaÂ (Capecitabine 500 mg by Roche Pharma AG, Germany)

ABSTRACT: Intervention1: Capecitabine 500mg (Relicitabine): Patients will be administered drug (Test or the Comparator depending on the Randomization sequence) on Day 1, Day 2, Day 3 of the study (in single treatment Cycle). The route of administration will be per oral Control Intervention1: XelodaÂ (Capecitabine 500mg Tablets) : Patients will be administered drug (Test or the Comparator depending on the Randomization sequence) on Day 1, Day 2, Day 3 of the study (in single treatment Cycle). The route of administration will be per oral Primary outcome(s): To establish the bioequivalence of Test vs Reference in relation to the rate and extent of absorption on the basis of the following pharmacokinetic parameters of Capecitabine during the course of study. PK sampling from Day1 to Day3. 12 PK samples in each period from 0 hours to 8 hours: â?¢ Cmax â?¢ AUC0-t Timepoint: To establish the bioequivalence of Test vs Reference in relation to the rate and extent of absorption on the basis of the following pharmacokinetic parameters of Capecitabine during the course of study. PK sampling from Day1 to Day3. 12 PK samples in each period from 0 hours to 8 hours: â?¢ Cmax â?¢ AUC0-t

DISEASE(S): Patients Of Locally Advanced Or Metastatic Breast Cancer Or Metastatic Colorectal Cancer Or Post-surgery Stage Iii (dukesâ?? Stage C) Colon Cancer

PROVIDER: 2575979 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

ACCESS DATA

Similar Datasets

Project description:Purpose: Decitabine is a deoxycytidine nucleoside derivative inhibitor of DNA-methyltransferases indicated for treatment of myelodysplastic syndrome (MDS). Laboratory evidence shows that pretreatment of AML cell lines can sensitize leukemia cells to chemotherapy and inhibit clonogenic potential. We conducted a randomized study of decitabine when used as priming before standard induction therapy in children with newly diagnosed acute myelogenous leukemia (AML) to evaluate the safety, pharmacokinetics, and any potential early efficacy signal. Exploratory analyses of genomic methylation and RNA expression patterns and minimal residual disease (MRD) were included to elucidate possible biological mechanisms. Methods: This multicenter, randomized, two-arm, open-label study enrolled children ages 1-16 with newly diagnosed de novo AML to either Arm A: daunorubicin, cytarabine, etoposide preceded by a 5-day course of decitabine (experimental arm) or Arm B: daunorubicin, cytarabine, etoposide (control). Following completion of induction therapy, subsequent post-induction treatment was given at the treating physician’s discretion. Patients were monitored for adverse events and samples were collected for PK/PD and biologic analyses. Results: Twenty patients, ages 1-16 years (median 9.4 yrs in both Arms) were treated (10 per Arm). Eighteen of 20 enrolled subjects completed the prescribed treatment. All subjects experienced neutropenia and thrombocytopenia as is expected during AML induction chemotherapy. The most common grade 3 and 4 non-hematologic adverse events observed were caecitis, 2 (20%) subjects in Arm A and 0 (0%) subjects in Arm B; decreased appetite, 3 (30%) subjects in Arm A and 0 (0%) subjects in Arm B; and hypophosphatemia, 2 (20%) subjects in Arm A and 0 (0%) subjects in arm B. One subject in Arm A had appendicitis and colon perforation on Day 6 that led to study discontinuation; the cause was later determined to have been leukemic infiltrate of the bowel wall. Two subjects died (both in Arm A), one of necrotic bowel, pseudomonas sepsis and multisystem organ failure 6 months after study participation and one patient 5 months following study treatment from multisystem organ failure as a complication of stem cell transplant. Plasma concentrations of decitabine showed PK values (mean+SD) of Cmax, 281+113 ng/mL, AUC0-∞, 198+65.3 ng*h/mL, CL, 156+94.6 L/h, Vdss 109+70 L, t1/2 0.48+0.060 h, and median tmax 0.93 h. Overall CR/CRi by morphology was similar between the two treatment arms (92% for the control arm and 100% for the experimental arm). MRD at Day 30 post induction therapy was lower in the control group compared to the decitabine group (67% vs 85% MRD-negative). Changes in DNA epigenetic and RNA expression patterns demonstrated distinct differences involving selective cellular pathways between the two groups of patients comparing diagnostic to day 30 bone marrow samples. Conclusions: This first-in-pediatric trial of epigenetic priming in patients with newly diagnosed AML demonstrates that decitabine pre-treatment followed by standard combination chemotherapy is well tolerated in children with newly diagnosed AML. Morphologic complete responses were similar in both treatment arms. MRD at Day 30 following induction therapy suggests a deeper remission in patients receiving decitabine. No differences were observed between treatment arms in hematologic toxicities although decitabine-treated patients were noted to have more gastrointestinal toxicities, anorexia and hypophosphatemia. Decitabine PK parameters in children were consistent with known adult PK profiles. Molecular changes associated with decitabine pretreatment may be important in the sensitization of clonogenic AML cells. Pre-treatment with decitabine may represent a therapeutic option for use in pediatric AML, when epigenetic modification is a desired focus for treatment.

Dataset Information

To study the effect of two drugs Capecitabine 500 mg (Test product by Reliance Life Sciences Pvt. Ltd., India) and XelodaÂ (Capecitabine 500 mg by Roche Pharma AG, Germany)

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets