There are 4 clinical trials
This is a phase I open label study to evaluate safety and efficacy of P1446A-05 in subjects with advanced refractory malignancies. Subjects of solid tumors or hematologic malignancies will be included. This is a dose escalation study following an accelerated titration design. It is expected that around 50 subjects would be enrolled in the study.Safety assessment will be conducted on the basis of vital signs, physical examination and laboratory investigations undertaken at regular intervals as per the schedule.
An Open Label, Multicenter Phase I Study Of Selective Cyclin Dependent Kinase Inhibitor P1446A-05 In Subjects With Advanced Refractory Malignancies. --- P1446A ---
A Study Of Selective Cyclin Dependent Kinase Inhibitor P1446A-05 In Subjects With Advanced Refractory Malignancies This is a phase I open label study to evaluate safety and efficacy of P1446A-05 in subjects with advanced refractory malignancies. --- P1446A ---
A Study Of Selective Cyclin Dependent Kinase Inhibitor P1446A-05 In Subjects With Advanced Refractory Malignancies This is a phase I open label study to evaluate safety and efficacy of P1446A-05 in subjects with advanced refractory malignancies. --- P1446A --- --- P1446A ---
To determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLT) of P1446A-05 in subjects with advanced refractory malignancies. --- P1446A ---
null. 1 To evaluate safety and tolerability ,pharmacokinetics of P1446A-05 in study population 2. To evaluate efficacy of P1446A-05 3. To perform exploratory analysis of biomarkers associated with use of P1446A-05 in the study population. --- P1446A ---
null. 1 To evaluate safety and tolerability ,pharmacokinetics of P1446A-05 in study population 2. To evaluate efficacy of P1446A-05 3. To perform exploratory analysis of biomarkers associated with use of P1446A-05 in the study population. --- P1446A --- --- P1446A ---
null. 1 To evaluate safety and tolerability ,pharmacokinetics of P1446A-05 in study population 2. To evaluate efficacy of P1446A-05 3. To perform exploratory analysis of biomarkers associated with use of P1446A-05 in the study population. --- P1446A --- --- P1446A --- --- P1446A ---
5. History of allergic reactions attributed to compounds of similar chemical structure to P1446A-05. --- P1446A ---
Solid Tumor Hematologic Malignancy Neoplasms This is a phase I open label study to evaluate safety and efficacy of P1446A-05 in subjects with advanced refractory malignancies. --- P1446A ---
Starting dose for P1446A-05 in this study is 75 mg orally once daily for 14 days followed by 7 days rest. --- P1446A ---
This constitutes one cycle for P1446A-05.Three patients will be enrolled in first cohort at this starting dose of P1446A-05. --- P1446A ---
This constitutes one cycle for P1446A-05.Three patients will be enrolled in first cohort at this starting dose of P1446A-05. --- P1446A --- --- P1446A ---
If this dose is well tolerated then dose escalation will be undertaken for subsequent cohorts as per accelerated titration design as described in protocol till maximum tolerated dose(MTD) for P1446A-05 is determined. --- P1446A ---
- An Open Label, Multicenter, Phase I Extension Study of an Oral Cdk Inhibitor P1446A-05 Administered with an Oral BRAF Inhibitor Vemurafenib (Zelboraf®) in Patients with Advanced or Inoperable Malignant Melanoma with BRAF Mutation - The primary objective is to determine the safety, maximum tolerated dose (MTD), and dose limiting toxicity (DLT) of the co-administration of P1446A-05 with vemurafenib, in melanoma patients with BRAF mutation
An Open Label, Multicenter, Phase I Extension Study of an Oral Cdk Inhibitor P1446A-05 Administered With an Oral BRAF Inhibitor Vemurafenib (Zelboraf®) in Patients With Advanced or Inoperable Malignant Melanoma With BRAF Mutation. --- P1446A ---
Study of an Oral Cdk Inhibitor Administered With an Oral BRAF Inhibitor in Patients With Advanced or Inoperable Malignant Melanoma With BRAF Mutation - An Open Label, Multicenter, Phase I Extension Study of an Oral Cdk Inhibitor P1446A-05 Administered with an Oral BRAF Inhibitor Vemurafenib (Zelboraf®) in Patients with Advanced or Inoperable Malignant Melanoma with BRAF Mutation - The primary objective is to determine the safety, maximum tolerated dose (MTD), and dose limiting toxicity (DLT) of the co-administration of P1446A-05 with vemurafenib, in melanoma patients with BRAF mutation Maximum Tolerated Dose and Dose Limiting Toxicity. --- P1446A ---
Study of an Oral Cdk Inhibitor Administered With an Oral BRAF Inhibitor in Patients With Advanced or Inoperable Malignant Melanoma With BRAF Mutation - An Open Label, Multicenter, Phase I Extension Study of an Oral Cdk Inhibitor P1446A-05 Administered with an Oral BRAF Inhibitor Vemurafenib (Zelboraf®) in Patients with Advanced or Inoperable Malignant Melanoma with BRAF Mutation - The primary objective is to determine the safety, maximum tolerated dose (MTD), and dose limiting toxicity (DLT) of the co-administration of P1446A-05 with vemurafenib, in melanoma patients with BRAF mutation Maximum Tolerated Dose and Dose Limiting Toxicity. --- P1446A --- --- P1446A ---
In the Dose escalation' phase patients will be co-administered P1446A-05 (150, 250, 350 mg qd) and vemurafenib (720, 960 mg bid) in a cohort of three to six patients on a 28-day cycle, until the occurrence of disease progression or unacceptable toxicity. --- P1446A ---
The maximum tolerated dose (MTD) of P1446A-05 and vemurafenib co-administered will be determined. --- P1446A ---
- To determine best Overall Response Rate (ORR), Duration of response (DOR), Progression Free Survival (PFS), and Overall Survival (OS) of the co-administration of P1446A 05 and vemurafenib using RECIST version 1.1 in melanoma patients with BRAF mutation. --- P1446A ---
The biomarkers will be assessed pre- and post-treatment and will focus on (a) inhibition of the MAPK pathway as a target of vemurafenib, a RAF inhibitor; (b) cell cycle pathways as an effect of P1446A-05, a Cdk inhibitor; (c) mechanisms of resistance; and (d) markers for senescence and apoptosis as evidence of target engagement/drug response. --- P1446A ---
Patients with a known immediate or delayed hypersensitivity reaction or idiosyncrasy to any other medication chemically related to P1446A-05 or vemurafenib, or excipients considered to be clinically significant by the investigator 12. Nursing woman 13. --- P1446A ---
Description: The study will be conducted in two phases- Phase I (Dose escalation phase), and Extension phase. In the Dose escalation' phase patients will be co-administered P1446A-05 (150, 250, 350 mg qd) and vemurafenib (720, 960 mg bid) in a cohort of three to six patients on a 28-day cycle, until the occurrence of disease progression or unacceptable toxicity. Escalation to the next higher dose during the dose escalation phase will depend upon demonstrated safety in the previous dose group. The maximum tolerated dose (MTD) of P1446A-05 and vemurafenib co-administered will be determined. In the 'Extension' phase, sixty patients with BRAF V600E/K mutations (forty patients naïve to selective BRAF inhibitor therapy, and twenty progressing on selective BRAF inhibitor therapy) will be treated at the MTD on a 28-day cycle, until the occurrence of disease progression or unacceptable toxicity to determine efficacy of the co-administration.
Measure: Maximum Tolerated Dose and Dose Limiting Toxicity Time: Until disease progression or unacceptable toxicity (expected to be 6-8 months)Description: - To determine best Overall Response Rate (ORR), Duration of response (DOR), Progression Free Survival (PFS), and Overall Survival (OS) of the co-administration of P1446A 05 and vemurafenib using RECIST version 1.1 in melanoma patients with BRAF mutation
Measure: Tumor Response Time: Until disease progression or unacceptable toxicity (expected to be 6-8 months)Description: PK parameters such as Cmax, Tmax, AUC0-t, AUC0-inf, Kel, CL, Vz and t1/2 will be determined using standard non-compartmental and population pharmacokinetic approach (wherever possible). Blood samples (6 mL at each time point) for pharmacokinetic assessment will be collected at the following time points in Dose Escalation Phase- Cycle 1- Day 15: pre-dose (within 30 min before swallowing the capsule/s, 1, 2, 4, 6, 8hr; Day 19: pre-dose (within 30 min before swallowing the capsule/s, 1, 2, 4, 8hr; and within one hour post dose on Day 22. Additionally, blood samples for PK analysis may be collected should patient develop SAE at the earliest feasible time point.
Measure: Pharmacokinetic (PK) Time: Cycle1 (Day 15 and 22) and Cycle 2 (Day1,15 and 28)Description: The biomarkers will be assessed pre- and post-treatment and will focus on (a) inhibition of the MAPK pathway as a target of vemurafenib, a RAF inhibitor; (b) cell cycle pathways as an effect of P1446A-05, a Cdk inhibitor; (c) mechanisms of resistance; and (d) markers for senescence and apoptosis as evidence of target engagement/drug response. During phase I dose escalation, optional tumor samples will be collected at screening, within 4 to 6 hours of drug administration on Day 14 of Monotherapy and between Cycle 1 Day 15 and Cycle 1 Day 21, and at disease progression After the MTD is determined, 10 additional patients will be enrolled in "Serial Tumor biopsy cohort" During the Extension phase, tumor samples will be collected at screening, Cycle 1 Day 15 and Cycle 1 Day 21 within 4 to 6 hours of drug administration, and at disease progression.
Measure: Biomarker Analysis Time: Until disease progression or unacceptable toxicity (expected to be 6-8 months)This is an open-label, Phase I/Ib trial with a dose escalation phase, followed by a dose extension phase. The objective of the dose escalation phase is to evaluate the pharmacokinetics (PK) and MTD of P1446A-05 in relapsed/refractory CLL and the objective of the dose extension phase is to evaluate the safety, efficacy and pharmacodynamics of P1446A-05 in 14 patients at the MTD level.
A Phase I/Ib Study of P1446A-05 in Patients With Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL).. Clinical Study of Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL) This is an open-label, Phase I/Ib trial with a dose escalation phase, followed by a dose extension phase. --- P1446A ---
The objective of the dose escalation phase is to evaluate the pharmacokinetics (PK) and MTD of P1446A-05 in relapsed/refractory CLL and the objective of the dose extension phase is to evaluate the safety, efficacy and pharmacodynamics of P1446A-05 in 14 patients at the MTD level. --- P1446A ---
The objective of the dose escalation phase is to evaluate the pharmacokinetics (PK) and MTD of P1446A-05 in relapsed/refractory CLL and the objective of the dose extension phase is to evaluate the safety, efficacy and pharmacodynamics of P1446A-05 in 14 patients at the MTD level. --- P1446A --- --- P1446A ---
To establish maximum tolerated dose (MTD) of P1446A 05 in patients with relapsed/refractory chronic lymphocytic leukemia (CLL). --- P1446A ---
In the 'dose extension phase', up to a total of 14 patients will be treated at the MTD of P1446A-05, determined in the 'dose escalation' phase, until the occurrence of disease progression or unacceptable toxicity or death. --- P1446A ---
To establish dose limiting toxicities (DLTs) of P1446A 05 in patients with relapsed/refractory chronic lymphocytic leukemia (CLL). --- P1446A ---
To determine the efficacy (overall response ) of P1446A 05 in patients with relapsed/refractory CLL. --- P1446A ---
To determine the efficacy (progression-free survival) of P1446A 05 in patients with relapsed/refractory CLL. --- P1446A ---
expression levels of Cyclin D1, p53 etc.) predict response to P1446A-05 in relapsed/refractory CLL. --- P1446A ---
P1446A-05 is both highly protein bound and a competitive inhibitor of CYP2C9 at higher concentrations and thus may potentiate the action of warfarin in patients 10. --- P1446A ---
Description: To establish maximum tolerated dose (MTD) of P1446A 05 in patients with relapsed/refractory chronic lymphocytic leukemia (CLL). There will be two phase, a dose escalation phase, followed by a dose extension phase. In the 'dose extension phase', up to a total of 14 patients will be treated at the MTD of P1446A-05, determined in the 'dose escalation' phase, until the occurrence of disease progression or unacceptable toxicity or death
Measure: Maximum Tolerated Dose Time: Cycle 1 (Day 1 to 28 )Description: To establish dose limiting toxicities (DLTs) of P1446A 05 in patients with relapsed/refractory chronic lymphocytic leukemia (CLL). - There will be two phase, a dose escalation phase, followed by a dose extension phase.
Measure: Dose Limiting Toxicity Time: Cycle 1 (Day 1 to 28 )Description: To determine the efficacy (overall response ) of P1446A 05 in patients with relapsed/refractory CLL. Overall Response will be assessed according to IWCLL 2008 criteria. Kaplan-Meier curve of overall survival will also be presented. OS will be evaluated in the dose extension phase only.
Measure: Overall response Time: At the end of every 2 cycles,Until disease progression or unacceptable toxicity (average of 2years)Description: To determine the efficacy (progression-free survival) of P1446A 05 in patients with relapsed/refractory CLL. Kaplan-Meier estimates of progression-free survival i.e. median and inter-quartile range will be presented. Kaplan-Meier curve of overall survival will also be presented. OS will be evaluated in the dose extension phase only.
Measure: Progression-free survival Time: At the end of every 2 cycles, until disease progression or unacceptable toxicity (average of 2years)Description: Samples for pharmacokinetic analysis for PK profile (Cmax,Tmax and AUC) will be collected on S-D1at pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, and 120 h post on Day S-D1 of single dose period (for Dose Levels 1, 2 and 3). In the continuous dose period, samples will be collected on Day 28 of Cycle 1 at pre-dose, and at 0.5, 2, 4, 6, 8 and 24 h post-dose. Additional samples will be collected pre dose on Day 15 and 22 of Cycle 1 to monitor the attainment of steady state. Pre-dose samples will also be collected on C2D15, C2D28, C3D15, C3D28 and C5D1. PK parameters will be obtained using standard non-compartmental methods. PK evaluations will not be performed in the dose extension phase. Descriptive statistics will be provided for the PK parameters. The PK analysis will be performed using WinNonlin software
Measure: Pharmacokinetic profile (Cmax,Tmax and AUC) Time: SD1, Cycle1-Cycle 5 (average of 5 month)Description: To assess whether established (IGHV, p53 and Notch mutational status and ZAP70 and CD38 expression,) and exploratory biomarkers (e.g. expression levels of Cyclin D1, p53 etc.) predict response to P1446A-05 in relapsed/refractory CLL
Measure: Biomarker Analysis Time: Cycle1Day1, Cycle1Day28, Until disease progression or unacceptable toxicity (average of 2years)This is a phase I study of a novel compound P1446A-05. Aim of this study is to identify the the recommended phase II dose of the drug and to determine the nature of adverse effects associated with the drug. P1446A-05 capsules will be given continuously (28 days in each 28 day cycle) to patients suffering from advanced malignancies with no effective treatment available. The dose of the study agent will be lower i.e. 75 mg per day for initial patients. If this dose is found safe, higher dose will be administered to next set of (three to six) patients. This will continued till the safest and best dose is identified. Treatment will be given for 4 cycles and continued further if found effective. Dose schedule may be modified to introduce treatment holiday,if frequent adverse effects are seen on continuous administration.
An Open Label, Multicenter Phase I Study Of Selective Cyclin Dependent Kinase Inhibitor P1446A-05 In Subjects With Advanced Refractory Malignancies. --- P1446A ---
A Multicenter Phase I Clinical Study of a New Compound P1446A-05 in Patients With Advanced Refractory Malignancies This is a phase I study of a novel compound P1446A-05. --- P1446A ---
A Multicenter Phase I Clinical Study of a New Compound P1446A-05 in Patients With Advanced Refractory Malignancies This is a phase I study of a novel compound P1446A-05. --- P1446A --- --- P1446A ---
P1446A-05 capsules will be given continuously (28 days in each 28 day cycle) to patients suffering from advanced malignancies with no effective treatment available. --- P1446A ---
- History of allergic reactions attributed to compounds of similar chemical structure to P1446A-05. --- P1446A ---