Ignite Creation Date:
2024-05-05 @ 5:26 PM
Last Modification Date:
2024-10-26 @ 9:31 AM
Study NCT ID:
NCT00450502
Status:
COMPLETED
Last Update Posted:
2019-12-05
First Post:
2007-03-20
Brief Title:
Safety of Batracylin in Patients With Solid Tumors and Lymphomas
Sponsor:
National Cancer Institute NCI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
A Phase I Study of Batracylin NSC320846 in Subjects With Solid Tumors and Lymphomas
Status:
COMPLETED
Status Verified Date:
2013-08-14
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Background
Batracylin advanced through the National Cancer Institute NCI drug development pipeline until its evaluation at Stage 3 on July 1989 It was then proposed for a phase I investigation based on its activity against as TOPO II inhibitor in sc mouse colon 38 PANC03 COLO9 and cisplatin- and doxorubicin-resistant P388 tumors
IND-directed oral toxicology studies indicated interspecies variation in toxicity Rats were found to be highly sensitive to batracylin Ames et al showed that the interspecies variation in toxicity was consistent with the pattern of metabolism of the compound by N-acetyltransferase 2 NAT2 to the acetylated form N-Ac-batracylin a highly toxic molecule
We hypothesize that batracylin can be administered safely in slow acetylator NAT2 genotype patients and can be rapidly evaluated for its potential as a tumor-suppressing agent
Objectives
Define the maximum tolerated dose dose-limiting toxicities and toxicity profile associated with the oral administration of batracylin daily x7 consecutive days repeated every 28 days in patients with solid tumors and lymphomas
Define the pharmacokinetics of oral batracylin administered daily x7 consecutive days every 28 days
Obtain preliminary evidence of anti-tumor activity of batracylin in patients with solid tumors or lymphoma
Correlate polymorphisms in slow acetylators NAT2 genotypes NAT2 5 NAT2 6 NAT2 7 and NAT2 14 with pharmacokinetics results
Evaluate the inter-subject variability and toxicity ratio N-Ac-Batra batracylin
Evaluate the effect of batracylin treatment on gamma-H2AX levels in tumor biopsies
Eligibility
Patients must have a slow acetylator NAT2 genotype defined as NAT2 5 NAT2 6 NAT2 7 or NAT2 14
Patients with advanced histologically confirmed malignancies refractory to standard therapy or those for whom no standard therapy exists
Patients should have adequate liver renal and bone marrow function
Study Design
In accordance with the accelerated titration design 4B3 dose levels will initially be increased at 100 increments and one new patient per dose level will be treated according to a 4-week course
The accelerated phase ends when one patient experiences dose limiting toxicity DLT during the first course of treatment or when two different patients experience grade 2 batracylin-related toxicity during the first course of treatment or when the N-acetyl-batra AUC value reach 033 uM-Hour ie the lower end of the range in the rat
When the first instance of grade 2 batracylin-related toxicity is observed two additional patients must have been treated at that dose or a higher dose during any course without experiencing moderate grade 2 or worse grade 3 toxicity in order for the accelerated phase to continue
When the accelerated phase ends the dose-escalation will revert to a more conservative modified Fibonacci scheme with 40 dose-step increments with at least 3 patients treated per dose level
Batracylin advanced through the National Cancer Institute NCI drug development pipeline until its evaluation at Stage 3 on July 1989 It was then proposed for a phase I investigation based on its activity against as TOPO II inhibitor in sc mouse colon 38 PANC03 COLO9 and cisplatin- and doxorubicin-resistant P388 tumors
IND-directed oral toxicology studies indicated interspecies variation in toxicity Rats were found to be highly sensitive to batracylin Ames et al showed that the interspecies variation in toxicity was consistent with the pattern of metabolism of the compound by N-acetyltransferase 2 NAT2 to the acetylated form N-Ac-batracylin a highly toxic molecule
We hypothesize that batracylin can be administered safely in slow acetylator NAT2 genotype patients and can be rapidly evaluated for its potential as a tumor-suppressing agent
Objectives
Define the maximum tolerated dose dose-limiting toxicities and toxicity profile associated with the oral administration of batracylin daily x7 consecutive days repeated every 28 days in patients with solid tumors and lymphomas
Define the pharmacokinetics of oral batracylin administered daily x7 consecutive days every 28 days
Obtain preliminary evidence of anti-tumor activity of batracylin in patients with solid tumors or lymphoma
Correlate polymorphisms in slow acetylators NAT2 genotypes NAT2 5 NAT2 6 NAT2 7 and NAT2 14 with pharmacokinetics results
Evaluate the inter-subject variability and toxicity ratio N-Ac-Batra batracylin
Evaluate the effect of batracylin treatment on gamma-H2AX levels in tumor biopsies
Eligibility
Patients must have a slow acetylator NAT2 genotype defined as NAT2 5 NAT2 6 NAT2 7 or NAT2 14
Patients with advanced histologically confirmed malignancies refractory to standard therapy or those for whom no standard therapy exists
Patients should have adequate liver renal and bone marrow function
Study Design
In accordance with the accelerated titration design 4B3 dose levels will initially be increased at 100 increments and one new patient per dose level will be treated according to a 4-week course
The accelerated phase ends when one patient experiences dose limiting toxicity DLT during the first course of treatment or when two different patients experience grade 2 batracylin-related toxicity during the first course of treatment or when the N-acetyl-batra AUC value reach 033 uM-Hour ie the lower end of the range in the rat
When the first instance of grade 2 batracylin-related toxicity is observed two additional patients must have been treated at that dose or a higher dose during any course without experiencing moderate grade 2 or worse grade 3 toxicity in order for the accelerated phase to continue
When the accelerated phase ends the dose-escalation will revert to a more conservative modified Fibonacci scheme with 40 dose-step increments with at least 3 patients treated per dose level
Detailed Description:
Background
Batracylin advanced through the National Cancer Institute NCI drug development pipeline until its evaluation at Stage 3 on July 1989 It was then proposed for a phase I investigation based on its activity against as TOPO II inhibitor in sc mouse colon 38 PANC03 COLO9 and cisplatin- and doxorubicin-resistant P388 tumors
IND-directed oral toxicology studies indicated interspecies variation in toxicity Rats were found to be highly sensitive to batracylin Ames et al showed that the interspecies variation in toxicity was consistent with the pattern of metabolism of the compound by N-acetyltransferase 2 NAT2 to the acetylated form N-Ac-batracylin a highly toxic molecule
We hypothesize that batracylin can be administered safely in slow acetylator NAT2 genotype patients and can be rapidly evaluated for its potential as a tumor-suppressing agent
Objectives
Define the maximum tolerated dose dose-limiting toxicities and toxicity profile associated with the oral administration of batracylin daily for 7 consecutive days repeated every 28 days in patients with solid tumors and lymphomas
Define the pharmacokinetics of oral batracylin administered daily for 7 consecutive days every 28 days
Obtain preliminary evidence of anti-tumor activity of batracylin in patients with solid tumors or lymphoma
Correlate polymorphisms in slow acetylators NAT2 genotypes NAT2 5 NAT2 6 NAT2 7 and NAT2 14 with pharmacokinetics results
Evaluate the inter-subject variability and toxicity ratio N-Ac-Batra batracylin
Evaluate the effect of batracylin treatment on gamma-H2AX levels in tumor biopsies
Eligibility
Patients must have a slow acetylator NAT2 genotype defined as NAT2 5 NAT2 6 NAT2 7 or NAT2 14
Patients with advanced histologically confirmed malignancies refractory to standard therapy or those for whom no standard therapy exists
Patients should have adequate liver renal and bone marrow function
Study Design
In accordance with the accelerated titration design 4B3 dose levels will initially be increased at 100 increments and one new patient per dose level will be treated according to a 4-week course
The accelerated phase ends when one patient experiences dose limiting toxicity DLT during the first course of treatment or when two different patients experience grade 2 batracylin-related toxicity during the first course of treatment or when the N-acetyl-batra AUC value reach 033 uM-Hour ie the lower end of the range in the rat
When the first instance of grade 2 batracylin-related toxicity is observed two additional patients must have been treated at that dose or a higher dose during any course without experiencing moderate grade 2 or worse grade 3 toxicity in order for the accelerated phase to continue
When the accelerated phase ends the dose-escalation will revert to a more conservative modified Fibonacci scheme with 40 dose-step increments with at least 3 patients treated per dose level
Batracylin advanced through the National Cancer Institute NCI drug development pipeline until its evaluation at Stage 3 on July 1989 It was then proposed for a phase I investigation based on its activity against as TOPO II inhibitor in sc mouse colon 38 PANC03 COLO9 and cisplatin- and doxorubicin-resistant P388 tumors
IND-directed oral toxicology studies indicated interspecies variation in toxicity Rats were found to be highly sensitive to batracylin Ames et al showed that the interspecies variation in toxicity was consistent with the pattern of metabolism of the compound by N-acetyltransferase 2 NAT2 to the acetylated form N-Ac-batracylin a highly toxic molecule
We hypothesize that batracylin can be administered safely in slow acetylator NAT2 genotype patients and can be rapidly evaluated for its potential as a tumor-suppressing agent
Objectives
Define the maximum tolerated dose dose-limiting toxicities and toxicity profile associated with the oral administration of batracylin daily for 7 consecutive days repeated every 28 days in patients with solid tumors and lymphomas
Define the pharmacokinetics of oral batracylin administered daily for 7 consecutive days every 28 days
Obtain preliminary evidence of anti-tumor activity of batracylin in patients with solid tumors or lymphoma
Correlate polymorphisms in slow acetylators NAT2 genotypes NAT2 5 NAT2 6 NAT2 7 and NAT2 14 with pharmacokinetics results
Evaluate the inter-subject variability and toxicity ratio N-Ac-Batra batracylin
Evaluate the effect of batracylin treatment on gamma-H2AX levels in tumor biopsies
Eligibility
Patients must have a slow acetylator NAT2 genotype defined as NAT2 5 NAT2 6 NAT2 7 or NAT2 14
Patients with advanced histologically confirmed malignancies refractory to standard therapy or those for whom no standard therapy exists
Patients should have adequate liver renal and bone marrow function
Study Design
In accordance with the accelerated titration design 4B3 dose levels will initially be increased at 100 increments and one new patient per dose level will be treated according to a 4-week course
The accelerated phase ends when one patient experiences dose limiting toxicity DLT during the first course of treatment or when two different patients experience grade 2 batracylin-related toxicity during the first course of treatment or when the N-acetyl-batra AUC value reach 033 uM-Hour ie the lower end of the range in the rat
When the first instance of grade 2 batracylin-related toxicity is observed two additional patients must have been treated at that dose or a higher dose during any course without experiencing moderate grade 2 or worse grade 3 toxicity in order for the accelerated phase to continue
When the accelerated phase ends the dose-escalation will revert to a more conservative modified Fibonacci scheme with 40 dose-step increments with at least 3 patients treated per dose level
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 07-C-0097 | None | None | None |